Study Evaluating the Safety, Efficacy and Tolerability of BIO89-100 in Subjects With Biopsy-confirmed Nonalcoholic Steatohepatitis (NASH): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating the Safety, Efficacy and Tolerability of BIO89-100 in Subjects With Biopsy-confirmed Nonalcoholic Steatohepatitis (NASH) (NCT04929483), a randomized phase 2 study. The primary outcome is Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group Phase 2 study. The registry record describes quadruple masking. The listed enrollment was 222, and the study status is completed. The record lists a start date of 2021-06-04 and a primary completion date of 2023-02-14.

The study evaluated BIO89-100 in participants with biopsy-confirmed NASH and fibrosis stages F2–F3. The intervention list names BIO89-100 and placebo. The main-study outcome tables use the name pegozafermin for the active-treatment arms and identify three schedules: 15 mg once weekly, 30 mg once weekly, and 44 mg once every 2 weeks. The primary comparison uses pooled placebo. The registry also lists placebo schedule groups and an extension description in which a placebo group received active treatment in the extension.

The primary endpoint was assessed at Week 24. In its full analysis set description, the registry specifies confirmed F2 or F3 fibrosis, baseline NAS ≥4, eligibility and randomization, and receipt of at least 1 dose of investigational product. Primary endpoint group sizes in the posted results are 14 for 15 mg once weekly, 53 for 30 mg once weekly, 43 for 44 mg once every 2 weeks, and 54 for pooled placebo. These analysis counts are not the same thing as the overall enrollment figure.

The original protocol’s sample-size justification, planned interim analyses, and detailed statistical analysis plan are not reported in the registry record. The posted record does identify the method used for the primary reported comparisons,.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Main Study (24 Weeks)

Reasons for not completing this period:

Extension Study (24 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of investigational product (IP). Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Randomized analysis set included all enrolled participants who were assigned a randomization number in the study.

6. Primary Endpoint

The registry lists the primary outcome as Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis, measured over Week 24.

The primary endpoint counts participants with histological resolution of NASH without worsening of fibrosis at Week 24. The definition combines two findings: resolution of the inflammatory and ballooning features of NASH, and no progression in fibrosis stage. The registry defines resolution as ballooning score 0 and inflammation score 0 to 1. Fibrosis worsening is progression by at least 1 stage on the NASH CRN scale, which ranges from 0 to 4.

The endpoint description also explains that NAS sums steatosis, inflammation, and ballooning scores, with values from 0 to 8 and higher scores indicating worse disease severity. NAS is relevant to the baseline eligibility criteria and other listed outcomes, while the primary endpoint’s resolution definition specifically refers to ballooning and inflammation, together with fibrosis status.

General statistical context: a histological endpoint can capture tissue-level features that are not represented by a single laboratory measurement. A combined endpoint also requires interpretation of each component and its operational definition. Here, a participant counted toward the primary outcome only if the stated NASH resolution criteria were met without the defined worsening of fibrosis. The registry record reports participant counts for that outcome by group. It does not describe additional endpoint adjudication details beyond the stated independent baseline review by a 3-pathologist panel.

7. Results Posted in the Registry

• Main Study: Pegozafermin 15 mg QW: 35.7% (5/14) versus 1.9% (1/54) on control; risk difference 33.9 percentage points (95% CI 8.5 to 59.2), risk ratio 19.29 (2.45–152.07); unadjusted two-proportion z-test p = <0.001.
• Main Study: Pegozafermin 30 mg QW: 22.6% (12/53) versus 1.9% (1/54) on control; risk difference 20.8 percentage points (95% CI 9.0 to 32.6), risk ratio 12.23 (1.65–90.75); unadjusted two-proportion z-test p = <0.001.
• Main Study: Pegozafermin 44 mg Q2W: 25.6% (11/43) versus 1.9% (1/54) on control; risk difference 23.7 percentage points (95% CI 10.2 to 37.3), risk ratio 13.81 (1.86–102.84); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Main Study: Pegozafermin 15 mg QW: 35.7% (5/14) versus 24.1% (13/54) on control; risk difference 11.6 percentage points (95% CI -15.9 to 39.2), risk ratio 1.48 (0.64–3.46); unadjusted two-proportion z-test p = 0.379.
  • Main Study: Pegozafermin 30 mg QW: 64.2% (34/53) versus 24.1% (13/54) on control; risk difference 40.1 percentage points (95% CI 22.9 to 57.3), risk ratio 2.66 (1.59–4.46); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Main Study: Pegozafermin 15 mg QW and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Main Study: Pegozafermin 30 mg QW than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Main Study: Pegozafermin 15 mg QW: 14.3% (2/14) versus 0.0% (0/54) on control; risk difference 14.3 percentage points (95% CI -4.0 to 32.6); unadjusted two-proportion z-test p = 0.005.
  • Main Study: Pegozafermin 30 mg QW: 13.2% (7/53) versus 0.0% (0/54) on control; risk difference 13.2 percentage points (95% CI 4.1 to 22.3); unadjusted two-proportion z-test p = 0.006.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Main Study: Pegozafermin 15 mg QW and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Main Study: Pegozafermin 30 mg QW than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Main Study: Number of Participants With at Least a 2-point Improvement in NAS Score and Are Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) Responders and Alanine Aminotransferase (ALT) Responders

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Main Study: Pegozafermin 15 mg QW: 28.6% (4/14) versus 9.3% (5/54) on control; risk difference 19.3 percentage points (95% CI -5.6 to 44.2), risk ratio 3.09 (0.95–10.00); unadjusted two-proportion z-test p = 0.057.
  • Main Study: Pegozafermin 30 mg QW: 58.5% (31/53) versus 9.3% (5/54) on control; risk difference 49.2 percentage points (95% CI 33.9 to 64.6), risk ratio 6.32 (2.66–15.01); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Main Study: Pegozafermin 15 mg QW and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Main Study: Pegozafermin 30 mg QW than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover histological response, combined histological and imaging or laboratory response, and lipid-related measures. Across the secondary endpoints with results, the broad pattern is that some active-treatment groups have more participants meeting response definitions than placebo, while the pattern is not uniform across every schedule or endpoint. The tables give the outcome-specific counts, estimates, confidence intervals, and p-values where reported; those should be consulted for the individual results rather than inferred from this summary.

These outcomes add context to the primary Week 24 endpoint because they examine related but distinct aspects of response. For example, a NAS improvement without fibrosis worsening is not the same outcome as NASH resolution without worsening of fibrosis. A combined response requiring NAS improvement alongside MRI-PDFF and ALT response has additional components. A result on one definition does not establish the result on another.

The registry lists 20 outcome measures, 18 posted secondary outcomes, and 6 analyses. The primary result should remain distinct from these additional outcomes. General statistical context: when many outcomes and comparisons are examined, the chance of obtaining at least one small p-value by chance can increase. The registry record does not report whether the secondary analyses followed a prespecified hierarchy or used an adjustment for multiple testing. Therefore, unadjusted secondary p-values carry less confirmatory weight than a result interpreted under a clearly stated multiplicity plan.

Secondary findings can be useful for describing consistency and identifying questions for further study, but they should not be treated as independent confirmation of the primary result. Differences in endpoint definitions, group sizes, and available analyses all matter. The posted secondary table is the appropriate place to review each endpoint’s estimate and uncertainty without collapsing unlike outcomes into one overall conclusion.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis
• Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage
• Main Study: Number of Participants With at Least a 2-point Improvement in NAS Score and Are Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) Responders and Alanine Aminotransferase (ALT) Responders
• Main Study: Percent Change From Baseline in Serum Triglycerides
• Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c)
• Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c)
• Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c)
• Main Study: Percent Change From Baseline in Adiponectin

9. Statistical Interpretation

10. Statistical Methods Explained

What is being compared? The primary outcome is binary: a participant either met the definition of NASH resolution without fibrosis worsening at Week 24 or did not. The posted group summaries therefore show counts of participants meeting the endpoint and the analysis group size. The calculated tables present these results and the comparisons; this discussion focuses on how to read them.

Risk differences and event counts

The recalculated comparison is an unadjusted risk difference. In general, a risk difference subtracts the observed event proportion in one group from the event proportion in the comparator group, with the ordering defined by the analysis. It expresses an absolute contrast rather than a relative one. The recalculated estimates in the table are expressed as proportions, while the registry-reported treatment differences are displayed on a different scale. Do not treat these figures as interchangeable without attending to their units and methods.

Because the primary endpoint is a count of participants meeting a binary definition, the evidence is driven by how many participants had the outcome in each group and how many were assessed in that group. General statistical context: when event counts are small, a small change in the number of observed events can meaningfully change an estimated contrast. The 15 mg once-weekly group and placebo group have few endpoint events in the posted results, so their estimates warrant particular attention to uncertainty rather than reliance on a single summary value.

Confidence intervals and p-values

A confidence interval gives a range of values compatible with the data under the analysis method and its assumptions. It is not a range that contains the true effect with a specified probability after the data have been observed. A narrower interval indicates greater precision on that scale; a wider interval signals more uncertainty. The interval should be read with the point estimate and with the definition of the comparison.

A p-value describes how unusual the data, or more extreme data, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry reports p-values for the primary comparisons and the table includes unadjusted recalculated p-values. They reflect different analyses and should not be conflated.

Registry-reported method

The registry identifies the Cochran-Mantel-Haenszel method for its reported primary comparisons. In general, this method can compare categorical outcomes across treatment groups while accounting for strata. The strata used in this study, and the details of any stratification or covariate adjustment, are not reported in the registry record. It is therefore not possible from this record alone to specify what variables the sponsor’s analysis accounted for.

The sponsor’s reported treatment differences and confidence intervals are the primary posted inferential results. The separate recalculated results are simple, unadjusted calculations from the posted summary counts. The record’s discrepancy indicator is false, but that does not make the two methods identical. The table is useful for seeing how an unadjusted contrast relates to the posted arm counts, while the sponsor’s own analysis remains the analysis reported by the registry.

Analysis population and endpoint definition

The primary endpoint uses the full analysis set described in the record. Participants were required to have confirmed F2 or F3 fibrosis and baseline NAS ≥4, to be eligible and assigned a randomization number, and to have received at least 1 dose of investigational product. The baseline confirmation was by independent review from a 3-pathologist panel. This definition helps readers understand which participants the result represents. It is not a full account of all analysis-set exclusions or missing-outcome handling; those details are not reported in the registry record.

General statistical context: an analysis population definition can affect the estimand—the precise question answered by an analysis. A full analysis set that requires treatment receipt may not include every randomized participant. The registry gives a concise population description, but does not state how participants with unavailable Week 24 histology were handled or whether sensitivity analyses were conducted.

What the method cannot establish

Neither a reported method nor a small p-value resolves questions about multiplicity, missing data, practical importance, or generalizability. The record lists multiple outcomes and analyses, but the planned hierarchy, any adjustment for multiple testing, and the original statistical analysis plan are not reported in the registry record. The method description also does not provide enough information to reconstruct the analysis in full. Accordingly, readers can describe the observed result and the posted inferential summaries, while keeping those unreported design and analysis details open.

11. Confidence Intervals and Precision

The confidence intervals show how much uncertainty remains around the estimated treatment contrasts. For the registry-reported primary analyses, the interval for 15 mg once weekly runs from 10.04 to 59.26; for 30 mg once weekly, from 9.05 to 32.72; and for 44 mg once every 2 weeks, from 10.04 to 37.18. Each is reported as a 95% confidence interval. The table also shows intervals for the unadjusted recalculations, on their own scale.

Intervals that span a wider range represent less precise estimates. The 15 mg once-weekly arm has 14 participants in the primary analysis, compared with 53 and 43 in the other active-treatment arms. The placebo group has 54 participants, but only 1 participant met the primary endpoint. Sparse counts limit how much precision can be obtained, especially for comparisons involving the smaller active group. The interval, rather than the point estimate by itself, conveys that uncertainty.

General statistical context: a 95% confidence interval is generated by a procedure that, under its assumptions, would cover the target parameter in 95% of repeated applications. It does not mean there is a 95% probability that this specific interval contains the true value. Nor does an interval quantify all uncertainty, such as uncertainty from unreported analysis choices, outcome ascertainment, or the applicability of the study population.

The reported and recalculated intervals arise from different methods and scales. Compare estimates and intervals within the corresponding analysis rather than mixing their endpoints. The registry’s p-values should likewise be interpreted alongside the relevant reported interval, not as a replacement for it. Overall, the intervals communicate evidence of a positive contrast in these posted analyses while also showing that the estimated size is not known precisely.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size display is a planning illustration based on the observed effect, not a record of the trial’s original design calculation. For binary outcomes like these, the displayed figures are participants per arm. The general assumptions stated for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column describes the corresponding planning target for a 90% chance. These are prospective planning quantities, not evidence about the probability that the completed study found a result or the probability that a finding is true.

Rows that plan for 100%, 75%, or 50% of the observed effect ask how the illustrative requirement changes when the target effect is the full observed size or a smaller fraction of it. Smaller effects generally require more participants to distinguish them from no difference under otherwise similar assumptions. This pattern is visible in the displayed planning rows. The displayed values are per arm, not total sample sizes, and they apply to each comparison separately rather than the multi-arm trial as a whole.

This is not observed power. It is a planning illustration computed from the observed effect and the stated assumptions. It should not be read as proof that the study was adequately or inadequately designed, because the design’s own assumptions and procedures are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.019; treatment proportion p₁ = 0.357; average p̄ = 0.188.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5524 = 1.0826.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4978 = 0.4189.
4. n = (1.0826 + 0.4189)² / (0.3386)² = 19.7, rounded up to 20 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0185185185185185                          # control proportion
p1 <- 0.357142857142857                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4929483)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 20 (80% power), 26 (90% power)
 75% of observed effect: n per arm = 30 (80% power), 39 (90% power)
 50% of observed effect: n per arm = 50 (80% power), 66 (90% power)
power.prop.test: 19.7 
Simulated power at n = 20 per arm: 0.881 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparisons using the Cochran-Mantel-Haenszel method, with treatment differences, 95% confidence intervals, and p-values. The posted reported estimates are 34.65 for 15 mg once weekly, 20.89 for 30 mg once weekly, and 23.61 for 44 mg once every 2 weeks. The corresponding p-values are < 0.001, 0.001, and 0.001.

The recalculations use only the posted summary counts to produce simple unadjusted risk differences. They are a transparent supplementary check, not a reconstruction of the sponsor’s analysis. Because the reported method and the recalculation differ, their estimates and intervals should be read in the scale and context shown in the tables. The record marks the discrepancy indicator as false; there is no flagged discrepancy between the posted values and the recalculation process.

For interpretation of the trial’s own inferential claim, the sponsor’s reported analysis is the relevant registry result. The recalculated numbers can help readers understand the crude contrast in the observed counts, but they do not replace the reported method or reveal unreported stratification, covariate handling, or missing-data decisions.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures and analyses, including the primary endpoint and secondary outcomes. However, the statistical analysis plan, planned testing hierarchy, and any procedure for controlling multiplicity are not reported in the registry record. It is therefore not possible to determine from this record whether the reported p-values were adjusted for the number of comparisons, or which outcomes were intended to be confirmatory.

General statistical context: when several hypotheses are tested, interpreting each p-value as if it were the only planned test can overstate the strength of evidence. A prespecified hierarchy or multiplicity adjustment can address this issue, but no such procedure should be assumed. The sponsor-reported primary p-values and unadjusted recalculated secondary comparisons should be read with this limitation in mind.

The primary population is described as a full analysis set comprising participants with confirmed fibrosis stage F2 or F3, baseline NAS ≥4, eligibility and randomization, and receipt of at least 1 dose of investigational product. The record does not provide a complete account of exclusions, the number with missing Week 24 biopsies, or how missing endpoint data were handled. Missing-data assumptions and any sensitivity analyses are not reported in the registry record.

These omissions limit independent assessment of the robustness of the analysis. For example, readers cannot tell from this record whether the primary analysis used imputation, a particular rule for unavailable outcomes, or a sensitivity analysis under alternative assumptions. Nor can the listed group counts alone establish how participants who did not contribute an endpoint were treated. The posted result remains interpretable as the reported analysis of the stated population, but its missing-data and multiplicity context is incomplete.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tibia fracture (5.3%), hypoglycaemia (5.3%), pancreatitis acute (4.8%), pneumonia (2.0%), angina pectoris (2.0%).

The safety summary reports serious adverse events for groups labelled with pegozafermin schedules and placebo exposure. In the listed groups, the numbers at risk and with a serious adverse event are 21 and 1 for 15 mg once weekly; 72 and 5 for 30 mg once weekly; 57 and 8 for 44 mg once every 2 weeks; 50 and 6 for placebo only; and 19 and 2 for placebo during the main study followed by 30 mg once weekly in the extension. The death count is 0 in each listed group.

The record also lists serious adverse-event terms and percentages, including tibia fracture, hypoglycaemia, acute pancreatitis, pneumonia, angina pectoris, and diastolic dysfunction. These terms are a summary across the reported safety data; the record excerpt does not assign each listed term to a particular treatment group. They should not be used to infer a comparative risk for an individual event.

General statistical context: safety counts describe events observed in the stated exposure groups and are not, by themselves, a causal comparison. The safety groups span main and extension study exposure, while the primary endpoint counts refer to the main study analysis. Differences in group definitions and exposure periods matter. The figures are descriptive and do not establish that an event was caused by a treatment or that risks are equivalent between groups.

17. What the Result Does, and Does Not, Mean

The posted results show that participants in each active-treatment group had more observed primary-endpoint events than participants in pooled placebo at Week 24. The registry’s reported Cochran-Mantel-Haenszel comparisons are labelled superiority, and all three reported p-values are below 0.001. The corresponding confidence intervals provide a range of estimates compatible with each reported analysis under its method.

That finding is specific to the endpoint definition, population, comparison, and time point in this record. It describes histological resolution of NASH without worsening of fibrosis among the specified full analysis set. It does not establish a result for participants outside the study eligibility criteria, for outcomes not reported, or for time points beyond Week 24. Nor does a statistical difference by itself indicate the size or importance of an effect for an individual participant.

General statistical context: statistical evidence and clinical importance are related but different questions. A p-value addresses compatibility with a null hypothesis under an analysis model; it does not say whether an effect matters to patients. The record does not provide a threshold for clinical importance. The confidence intervals also show that the estimated treatment contrasts retain uncertainty, particularly where group sizes or event counts are limited.

The primary result should not be used to infer that every secondary endpoint had the same pattern, that all treatment schedules are equivalent, or that every participant would experience the endpoint. Secondary outcomes have separate definitions and their own uncertainty. The absence of reported deaths in the listed safety groups does not establish the absence of other risks, and the serious adverse-event summaries do not by themselves establish comparative causality.

Finally, details that would help assess the strength and scope of inference—including the original analysis plan, multiplicity handling, and missing-data methods—are not reported in the registry record. The appropriate conclusion is therefore a description of the posted findings and their precision, without extending them beyond the trial’s measured outcomes and population.

18. Why This Trial Matters Statistically

This study illustrates why a clinical-trial result should be read through several layers: what counted as an outcome, who entered the analysis, how treatment groups were compared, and how much uncertainty remains. Here the primary outcome is not simply a change in a score. It requires NASH resolution under a defined histological rule and no worsening of fibrosis. That operational definition determines what the event counts mean.

It also shows the distinction between a registry-reported analysis and a simple recalculation from summary counts. The reported comparison uses the Cochran-Mantel-Haenszel method, while the recalculation is an unadjusted risk difference. Both can help describe the posted data, but they answer through different analytic procedures and should not be substituted for one another.

The group sizes and event counts make precision central to interpretation. A positive direction in observed counts and small reported p-values do not remove uncertainty about the magnitude of the contrast. Confidence intervals, the analysis population, and the limited number of endpoint events are part of the result, not optional details.

Finally, the record lists many secondary outcomes but does not report the multiplicity plan or missing-data methods. This is a practical example of why conclusions from a set of trial results depend not only on the visible estimates, but also on prespecification and analysis details. Distinguishing reported details from unreported methods helps readers avoid turning a registry summary into a broader claim than it supports.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The posted primary analysis has unequal group sizes, including 14 participants in the 15 mg once-weekly arm, and few primary endpoint events in the placebo group. This limits precision for some comparisons. The interval estimates should therefore be considered alongside the observed counts rather than relying on a point estimate or p-value alone.

The registry record does not report the original sample-size justification, statistical analysis plan, interim-analysis plan, multiplicity strategy, or missing-data handling. It also does not describe the strata underlying the Cochran-Mantel-Haenszel analysis. These omissions restrict independent reconstruction of the sponsor’s analysis and assessment of robustness to alternative assumptions.

The primary analysis population requires participants to have received at least 1 dose, in addition to eligibility, randomization, and specified baseline histology. The record does not provide enough detail to determine how every randomized participant with unavailable Week 24 histology was handled. The overall enrollment figure and the endpoint analysis group sizes consequently describe different aspects of the study.

The record uses BIO89-100 in the intervention list and pegozafermin in the posted outcome-arm labels. Both names appear in the record, but it does not explain the naming difference. The safety summaries combine main and extension exposure groups, which are not the same group definitions as the primary endpoint table. This makes direct comparisons between efficacy and safety counts inappropriate.

Finally, the primary endpoint is histological and assessed at Week 24. The registry summary does not establish how these results relate to longer-term outcomes or to populations not represented by the stated eligibility criteria. These are limits on what can be concluded from this record, not evidence against the posted findings.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Evaluating the Safety, Efficacy and Tolerability of BIO89-100 in Subjects With Biopsy-confirmed Nonalcoholic Steatohepatitis (NASH) — NCT04929483.
• Registry record last updated 2026-01-06; status last verified 2025-12.
• Results first posted 2026-01-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

This completed randomized, double-blind, placebo-controlled Phase 2 study evaluated BIO89-100 in participants with biopsy-confirmed NASH. The primary endpoint was histological resolution of NASH without worsening of fibrosis at Week 24. The posted main-study results include three active-treatment schedules and pooled placebo.

The registry reports Cochran-Mantel-Haenszel comparisons for the primary endpoint, with positive treatment-difference estimates and p-values below 0.001 for all three active-treatment comparisons. Unadjusted recalculations from posted counts are also displayed as supplementary analyses. The confidence intervals and relatively small event counts remain important when interpreting the estimated differences.

Secondary outcomes cover additional histological, imaging, laboratory, and lipid measures. The registry record does not report the original statistical plan, multiplicity procedure, or missing-data strategy. Safety summaries include serious adverse-event counts and zero deaths in each listed group. Overall, this page describes the posted results and their uncertainty without extending the conclusions beyond the measured outcomes and study population.