Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis (NCT04048876), a randomized phase 2 study. The primary outcome is Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52.

2. Clinical Question

The study was designed to assess fibrosis and other efficacy measures, examine dose response, and assess overall safety. Its primary question is a binary response question: each participant either met the stated improvement criterion or did not. The endpoint specifies that a change of ≤ -1 from baseline in fibrosis stage counts as an improvement response.

The registry reports 56 participants enrolled across the four assigned groups. The posted Week 52 response percentages were 15.4% for CC-90001 100 mg, 0.0% for 200 mg, 7.7% for 400 mg, and 6.7% for placebo. These are observed group percentages, not estimates from a large sample. The small group sizes mean that a change in the outcome of only a few participants could materially change the percentages. The confidence intervals and between-group estimates therefore matter alongside the percentages themselves.

The statistical question is whether the posted data distinguish each dose group’s response from the placebo response with useful precision. The registry record does not report an adjusted sponsor analysis for these comparisons. The unadjusted recalculations are descriptive evidence from this small study, not a definitive assessment of efficacy or dose response.

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter, multinational, dose-finding study. The registry describes a parallel-group model and quadruple masking. The intended comparison was CC-90001 at three once-daily doses against once-daily placebo in participants with NASH and Stage 2 or Stage 3 liver fibrosis.

The four groups were CC-90001 100 mg, CC-90001 200 mg, CC-90001 400 mg, and placebo. The primary outcome was assessed from baseline up to Week 52. The registry reports an enrollment of 56: 13 participants in the 100 mg group, 15 in the 200 mg group, 13 in the 400 mg group, and 15 in the placebo group for the primary outcome. The registry identifies the primary outcome population as the Full Analysis Set, but its operational definition is not reported in the registry record.

The registry lists a study start date of 2019-08-14 and a primary completion date of 2021-09-28. The status is terminated. The reason for termination, the timing of termination relative to planned study activities, and any effect on the analysis are not reported in the registry record. The record describes the study as dose-finding, but the specific original sample-size justification and the planned statistical approach to dose response are not reported in the registry record.

Randomization and masking are design features intended to support balanced comparisons and reduce the influence of expectations or knowledge of assignment. Those features do not remove the uncertainty caused by small group sizes or sparse outcome events. The record lists 19 outcome measures and 18 posted secondary outcomes. It contains no reported analysis records. Consequently, the posted group summaries are important, but they do not supply all the detail needed to assess the full analysis plan or the handling of participants and observations in every analysis.

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.

Placebo Controlled Phase

Reasons for not completing this period:

Active Treatment Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52, measured over From baseline up to week 52.

The primary endpoint is the percentage of participants who achieved at least one stage of improvement in liver fibrosis by Week 52, using the NASH CRN Histological Scoring System. A change of ≤ -1 from baseline in fibrosis stage qualifies as an improvement response. The system describes fibrosis stages from Stage 0, none, through Stage 4, cirrhosis; intermediate stages include different patterns of fibrosis and bridging fibrosis.

This endpoint turns a change in a histological fibrosis score into a responder outcome. A percentage is straightforward to interpret as the share of participants in a group who met a prespecified response definition. The threshold also distinguishes participants who meet the criterion from those who do not, rather than reporting the size of each participant’s score change. That distinction is useful for a group comparison, but it means the endpoint does not describe every aspect of liver histology or the magnitude of improvement among responders.

The primary outcome is one measure of treatment response, not a complete account of disease status. The study also listed outcomes concerning steatohepatitis, total NAS, NASH resolution, cirrhosis progression, biochemistry, metabolic parameters, and Cmax. Those measures address related but distinct questions. The registry’s endpoint definition identifies the Full Analysis Set, but how that set was constructed and how missing Week 52 assessments were handled are not reported in the registry record.

7. Results Posted in the Registry

• CC-90001 100mg: 15.4% (2/13) versus 6.7% (1/15) on control; risk difference 8.7 percentage points (95% CI -14.6 to 32.0), risk ratio 2.31 (0.24–22.62); unadjusted two-proportion z-test p = 0.457.
• CC-90001 200mg: 0.0% (0/15) versus 6.7% (1/15) on control; risk difference -6.7 percentage points (95% CI -19.3 to 6.0); unadjusted two-proportion z-test p = 0.309.
• CC-90001 400mg: 7.7% (1/13) versus 6.7% (1/15) on control; risk difference 1.0 percentage points (95% CI -18.2 to 20.2), risk ratio 1.15 (0.08–16.67); unadjusted two-proportion z-test p = 0.916.

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.

Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CC-90001 100mg: 15.4% (2/13) versus 6.7% (1/15) on control; risk difference 8.7 percentage points (95% CI -14.6 to 32.0), risk ratio 2.31 (0.24–22.62); unadjusted two-proportion z-test p = 0.457.
  • CC-90001 200mg: 0.0% (0/15) versus 6.7% (1/15) on control; risk difference -6.7 percentage points (95% CI -19.3 to 6.0); unadjusted two-proportion z-test p = 0.309.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CC-90001 100mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CC-90001 200mg and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Improvement in Total NAS

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CC-90001 100mg: 7.7% (1/13) versus 13.3% (2/15) on control; risk difference -5.6 percentage points (95% CI -28.1 to 16.8), risk ratio 0.58 (0.06–5.66); unadjusted two-proportion z-test p = 0.630.
  • CC-90001 200mg: 6.7% (1/15) versus 13.3% (2/15) on control; risk difference -6.7 percentage points (95% CI -28.0 to 14.7), risk ratio 0.50 (0.05–4.94); unadjusted two-proportion z-test p = 0.543.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CC-90001 100mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CC-90001 200mg and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Resolution of NASH

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CC-90001 100mg: 15.4% (2/13) versus 6.7% (1/15) on control; risk difference 8.7 percentage points (95% CI -14.6 to 32.0), risk ratio 2.31 (0.24–22.62); unadjusted two-proportion z-test p = 0.457.
  • CC-90001 200mg: 0.0% (0/15) versus 6.7% (1/15) on control; risk difference -6.7 percentage points (95% CI -19.3 to 6.0); unadjusted two-proportion z-test p = 0.309.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CC-90001 100mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CC-90001 200mg and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes address several related aspects of NASH and liver disease rather than repeating the primary fibrosis response question alone. They include a combined steatohepatitis and fibrosis response, improvement in total NAS, resolution of NASH, resolution of NASH without worsening fibrosis, progression to cirrhosis, changes in liver biochemistry and metabolic parameters, and Cmax. The record lists 18 posted secondary outcomes, although detailed group results are not available for every listed measure in the material analyzed.

Across the secondary outcomes with detailed binary results, the pattern is mixed across doses and measures. The combined outcome of no worsening of steatohepatitis with at least one stage of fibrosis improvement has the same posted group values as the primary endpoint. The other detailed binary measures do not show a consistent ordering across the dose groups. This broad pattern does not resolve the uncertainty in the primary endpoint or establish a clear dose-response pattern.

Secondary outcomes can add context because they examine different dimensions of disease response. They do not automatically confirm or overturn the primary result: each measure has its own definition, event frequency, and uncertainty. General statistical principle: multiple outcomes and dose comparisons create more opportunities for chance variation to appear noteworthy. Without a reported testing hierarchy or adjustment, individual unadjusted secondary comparisons should be treated as exploratory rather than independent confirmatory evidence.

The registry record contains no reported analysis records. It does not report how the secondary outcomes were prioritized, whether any were intended for formal hypothesis testing, or how multiplicity was to be handled. The secondary findings are therefore most useful as descriptive context and as a guide to questions that would require a fully documented analysis, rather than as stand-alone evidence of treatment effect.

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

• Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52
• Percentage of Participants With Improvement in Total NAS
• Percentage of Participants With Resolution of NASH
• Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis
• Percentage of Participants Who Progressed to Cirrhosis
• Mean Change From Baseline in Liver Biochemistry
• Mean Change From Baseline in Metabolic Parameters
• Cmax

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: participants either meet the fibrosis-improvement response definition or do not. For each group, the registry reports the percentage meeting the definition and a 95% confidence interval. The comparison with placebo is expressed as a risk difference. The posted comparison results and p-values discussed in the interpretation are unadjusted recalculations from the group summaries; the registry record does not list reported analysis records.

What does a response percentage describe?

A response percentage describes the observed fraction of participants in a group who met the endpoint definition. It is a direct summary of the observed data, but it is not automatically a precise estimate of the response proportion in a wider population. Precision depends in part on how many participants contribute data and how many responses occur. General statistical principle: with small samples and few events, each participant’s outcome has relatively strong influence on the observed percentage.

For the primary outcome, the observed responder counts were 2 of 13 in the 100 mg group, 0 of 15 in the 200 mg group, 1 of 13 in the 400 mg group, and 1 of 15 in the placebo group. Those counts explain why the group percentages should not be interpreted as finely measured rates. The registry gives group-level confidence intervals, but it does not describe the interval construction method in the registry record.

What does the risk difference compare?

A risk difference compares the response proportions in two groups by subtracting the comparator proportion from the intervention proportion. A value of zero represents equal observed proportions on this scale. A positive value indicates a larger observed proportion in the CC-90001 group; a negative value indicates a smaller observed proportion. General statistical principle: unlike a relative measure, a risk difference expresses the contrast on the absolute proportion scale, which can make the direction and size of a group contrast easier to interpret directly.

The primary endpoint recalculations give risk differences of 0.087 for 100 mg versus placebo, -0.067 for 200 mg versus placebo, and 0.010 for 400 mg versus placebo. Their confidence intervals include zero, so the posted data remain compatible with no difference on this scale as well as with differences in either direction. The p-values are unadjusted and should not be read as the probability that a treatment effect is true or as a measure of effect size.

How should confidence intervals be read?

A confidence interval expresses uncertainty around an estimate under the statistical procedure used to construct it. General statistical explanation: a 95% confidence interval is generated by a method designed to cover the true parameter in 95% of repeated applications under its assumptions. It is not a guarantee that a particular interval contains the true value, and it does not assign a probability to the true value after the data have been observed.

For a risk difference, an interval that includes zero indicates that the data do not sharply separate a positive contrast from no contrast or a negative contrast. The interval’s width is also important: broad intervals leave a wide range of plausible effects. Here, the primary risk-difference intervals extend across zero and cover substantial values on both sides. General statistical principle: sparse binary outcomes commonly yield less precise estimates, especially when group sizes are small.

What does an unadjusted p-value contribute?

A p-value describes how unusual the observed data, or data more extreme, would be under a specified null model and its assumptions. It does not measure the probability that the null hypothesis is true, and it does not establish whether an effect is clinically important. The recalculated primary comparison p-values are 0.457, 0.309, and 0.916 for the 100 mg, 200 mg, and 400 mg comparisons with placebo, respectively. These are unadjusted results. The registry record does not report a sponsor-defined testing hierarchy or multiplicity adjustment for the comparisons.

General statistical principle: when several outcomes, doses, or contrasts are examined, repeated testing can increase the chance of finding a seemingly notable result by chance. That is one reason unadjusted secondary results should carry less weight than a prespecified primary analysis with a clearly documented testing plan. The number of posted outcomes makes the absence of a reported multiplicity plan relevant to interpretation, but it does not establish which approach the sponsor intended.

Why do sparse events matter?

When the event is uncommon and the sample is small, estimates can be sensitive to whether one or two participants meet the endpoint. The observed primary response counts range from zero to two within the individual groups. General statistical principle: sparse data can produce wide confidence intervals and unstable relative measures; an apparently large relative contrast may be driven by very few events. The registry includes relative measures for some recalculated comparisons, but the absolute risk-difference estimates and their intervals are the focus of the primary interpretation.

These methods explain the posted summaries without filling gaps in the protocol. The original analysis model, sample-size justification, handling of missing data, prespecified adjustment strategy, and analysis of dose response are not reported in the registry record. The available recalculations therefore support a cautious reading of the observed results, not reconstruction of the sponsor’s complete statistical plan.

11. Confidence Intervals and Precision

The primary endpoint estimates are imprecise. The 95% confidence intervals for the response percentages are 1.92 to 45.45 for CC-90001 100 mg, 0.0 to 21.8 for 200 mg, 0.19 to 36.03 for 400 mg, and 0.17 to 31.95 for placebo. These wide ranges show that the observed percentages do not tightly determine the underlying group response proportions.

The 95% confidence intervals for the unadjusted risk differences also include zero: -0.146 to 0.320 for 100 mg versus placebo, -0.193 to 0.060 for 200 mg versus placebo, and -0.182 to 0.202 for 400 mg versus placebo. Thus, the data do not precisely establish the direction of any of these contrasts. Each interval allows for values on both sides of no difference.

General statistical explanation: interval width reflects uncertainty under the method used and is affected by sample size, event frequency, and the analysis assumptions. A narrow interval would indicate greater precision; a wide interval leaves more plausible values unresolved. These intervals are not evidence that every value they contain is equally likely, nor do they indicate the probability that a particular treatment effect is true.

The small group sizes and sparse responder counts are central to the uncertainty. A point estimate can look higher or lower than placebo while still being accompanied by an interval that includes a broad range of possible effects. The registry record does not report a sponsor analysis that could add model-based adjustment or clarify the precision under a prespecified approach. The intervals are therefore best read as a warning against over-interpreting differences in the observed percentages.

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 planning illustrations express sample size as participants per arm for the binary-outcome comparisons. They are not total event counts. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm under which the stated planning assumptions would yield an 80% chance of detecting the specified effect if that effect were real. The 90% power column uses a higher chance of detection under those assumptions and therefore generally calls for more participants per arm. These are planning illustrations based on observed effects, not a description of the study’s original design.

For the primary comparison of 100 mg with placebo, planning for 100% of the observed effect gives 202 participants per arm for 80% power and 270 participants per arm for 90% power. Planning for 75% of the observed effect gives 328 participants per arm for 80% power and 438 participants per arm for 90% power; planning for 50% gives 666 participants per arm for 80% power and 890 participants per arm for 90% power. For the 400 mg comparison, the corresponding 100%-of-observed-effect figures are 9,944 and 13,311 participants per arm. These figures illustrate how strongly the calculation depends on the observed contrast.

Smaller effects require more participants to distinguish them from no difference under otherwise unchanged assumptions. The listed illustrations use the observed effect as their starting point, so they should not be treated as evidence that the trial had a particular probability of success. This is not observed power. It is a planning aid, and it does not replace the uncertainty shown by the confidence intervals or establish what sample size the sponsor originally intended.

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 = 0.067; treatment proportion p₁ = 0.154; average p̄ = 0.110.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4429 = 0.8682.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4386 = 0.3692.
4. n = (0.8682 + 0.3692)² / (0.0872)² = 201.4, rounded up to 202 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 <- 0.0666666666666667                          # control proportion
p1 <- 0.153846153846154                          # 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(4048876)
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 = 202 (80% power), 270 (90% power)
 75% of observed effect: n per arm = 328 (80% power), 438 (90% power)
 50% of observed effect: n per arm = 666 (80% power), 890 (90% power)
power.prop.test: 201.4 
Simulated power at n = 202 per arm: 0.807 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint alongside numerous secondary outcomes and compares three CC-90001 dose groups with placebo. These multiple outcomes and contrasts create a multiplicity issue: when many statistical questions are examined, some results may appear unusual by chance even if there is no underlying effect. General statistical principle: a prespecified testing hierarchy or adjustment can control how evidence is interpreted across multiple tests. The registry record does not report such a hierarchy or multiplicity adjustment.

There are no reported analysis records in the registry. The posted comparisons discussed in this analysis are unadjusted recalculations from summary statistics, not a sponsor-reported adjusted analysis. The record does not report whether the sponsor used a different model, what test was planned for the primary outcome, or whether secondary outcomes were intended to be confirmatory or exploratory. Those details are not reported in the registry record and cannot be inferred from the posted summaries.

The primary outcome identifies the Full Analysis Set, but the registry record does not provide its operational definition or a participant accounting for every analysis. The outcome data show group denominators, but the record does not report how missing Week 52 assessments were handled, whether any participants were excluded from the endpoint analysis, or what assumptions were used for missing outcomes. These omissions matter because the treatment of missing data can affect both the estimated response percentages and their uncertainty.

The status is terminated, but the reason and its implications for planned analyses are not reported in the registry record. It is also not reported whether interim analyses took place. The absence of these details does not prove that a particular method was or was not used; it means the registry record does not allow readers to evaluate it. These uncertainties are especially relevant when interpreting unadjusted findings across several outcomes and dose comparisons.

15. 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: appendicitis (7.7%), covid-19 (7.7%), ligament sprain (7.7%), spinal retrolisthesis (7.7%), abdominal pain (6.7%).

The registry reports serious adverse event counts among participants at risk of these events. The counts were 2 among 13 in the 100 mg group, 1 among 15 in the 200 mg group, 2 among 13 in the 400 mg group, and 0 among 15 in the placebo group. It also reports other adverse event counts of 10 among 13, 13 among 15, 12 among 13, and 10 among 15, respectively. No deaths were reported in these four groups.

The record separately lists active-treatment phases of CC-90001 200 mg and 400 mg following placebo, with one participant at risk and one participant with an other adverse event in each group; no serious adverse events or deaths are reported for either group. These entries should be kept distinct from the original randomized groups when reading the safety counts.

Serious-event terms listed in the registry include appendicitis, COVID-19, ligament sprain, spinal retrolisthesis, abdominal pain, and constipation, with reported percentages. The record does not establish that a listed event was caused by study treatment. These counts describe reported events and should not be interpreted as comparative proof of safety or harm. The small groups and absence of a reported safety analysis limit what can be concluded from the counts.

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

The posted results describe a small Phase 2 comparison of three CC-90001 doses with placebo on a Week 52 liver-fibrosis response outcome. The observed response percentages were 15.4% at 100 mg, 0.0% at 200 mg, 7.7% at 400 mg, and 6.7% with placebo. The unadjusted risk-difference intervals include zero for all three dose comparisons and are broad. The data therefore do not precisely establish a difference from placebo or a consistent dose-response pattern.

That interpretation is not the same as claiming that there is no effect. The intervals permit a range of possible effects in both directions, and the group sizes are small. Conversely, a numerically higher response in one group is not sufficient to establish an effect. A point estimate is one summary of the observed sample; the confidence interval and the limited number of responses show how uncertain that estimate remains.

The endpoint captures a defined histological improvement threshold. It does not by itself describe all changes in NASH, liver function, symptoms, or long-term outcomes. The study listed other efficacy and safety measures, but the registry record does not supply reported analysis records or a fully documented plan for interpreting all outcomes together.

The safety counts are descriptive. They do not establish whether an event was caused by treatment, and the small groups do not support broad conclusions about comparative safety. The record reports no deaths in the randomized groups, but that observation does not settle other safety questions.

Overall, the registry data are useful for understanding what was observed and how uncertain the estimates are. They do not provide a definitive answer about efficacy, dose response, or comparative safety. The reason for termination, original sample-size justification, missing-data procedures, interim analyses, and sponsor analysis plan are not reported in the registry record, limiting assessment of how the posted summaries relate to the full trial conduct.

17. Why This Trial Matters Statistically

This trial illustrates an important statistical distinction between an observed percentage and a precise estimate. The primary outcome percentages may appear easy to compare, but they arise from groups of 13 or 15 participants and only a few responders. In that setting, a small change in the observed count can substantially alter the percentage. The broad confidence intervals make the resulting uncertainty visible.

The comparison also shows why direction and precision should be considered together. The 100 mg group’s observed response percentage was above placebo, the 200 mg group’s was below placebo, and the 400 mg group’s was close to placebo. Yet the risk-difference intervals for all three comparisons span zero and substantial values on both sides. The observed ordering does not establish a dose-response pattern.

The study has multiple doses and many outcome measures. That structure makes transparent reporting of the analysis plan and multiplicity approach particularly useful. The registry record lists outcomes but contains no reported analysis records; it also does not report the original sample-size justification, missing-data procedures, or reason for termination. These gaps do not negate the posted data, but they limit the strength of conclusions that can be drawn from them.

The planning illustrations further demonstrate how sensitive sample-size calculations are to the effect size assumed. Figures based on the full observed effect differ from those based on smaller fractions of it, emphasizing that future planning requires a defensible target effect rather than uncritical reliance on a small study’s point estimate. This is a statistical lesson about uncertainty and design, not a conclusion about whether the treatment is beneficial.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint groups are small, with only a few observed responses in each group. This leads to wide confidence intervals and leaves substantial uncertainty about the underlying response rates and risk differences. The registry does not report adjusted sponsor analyses, so the comparisons discussed are unadjusted recalculations from posted summaries.

The record lists multiple secondary outcomes and dose comparisons, but it does not report a testing hierarchy or multiplicity adjustment. The secondary results therefore need cautious interpretation. The record also does not describe the original sample-size justification, the planned analysis model, or whether interim analyses were conducted.

The endpoint population is named as the Full Analysis Set, but the criteria defining that set are not reported in the registry record. The handling of missing Week 52 observations, participant exclusions, and missing-data assumptions is also not reported. These gaps prevent a full assessment of how analysis populations and missing observations may have affected the endpoint estimates.

The study status is terminated, but the reason for termination and its relationship to recruitment, follow-up, or analysis are not reported in the registry record. The safety counts are descriptive and come from small groups; the record does not provide a reported comparative safety analysis or establish event causality. Finally, the primary endpoint measures a specific fibrosis-stage response and does not summarize every clinically relevant outcome listed for the study.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis — NCT04048876.
• Registry record last updated 2023-06-07; status last verified 2023-06.
• Results first posted 2023-06-07.
• 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.

22. Record Summary

NCT04048876 is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, multinational, parallel-group dose-finding study of CC-90001 in participants with NASH and Stage 2 or Stage 3 liver fibrosis. The study compared once-daily doses of 100 mg, 200 mg, and 400 mg with placebo. Enrollment was 56, and the registry status is terminated.

The primary endpoint was the percentage achieving at least one stage of improvement in liver fibrosis at Week 52. Posted response percentages were 15.4%, 0.0%, 7.7%, and 6.7% for the 100 mg, 200 mg, 400 mg, and placebo groups, respectively. Unadjusted recalculated risk-difference intervals include zero and are broad. The registry record contains no reported analysis records; the reason for termination, original design assumptions, missing-data methods, and multiplicity plan are not reported in the registry record.