Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients With Nash Cirrhosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients With Nash Cirrhosis (NCT02462967), a randomized phase 2 study. The primary outcome is Change in Portal Pressure at Year 1 (Change in HVPG From Baseline and 1 Year).

2. Clinical Question

The trial asks whether change in portal pressure over one year differed between participants assigned to either of two GR-MD-02 doses and participants assigned to placebo. Portal pressure was assessed as the hepatic venous pressure gradient (HVPG), with the primary endpoint defined as change from baseline.

The registry record describes a multicenter, randomized, placebo-controlled, parallel-group study. The trial enrolled 162 participants. The clinical question is specific to the selected study population and the one-year endpoint; results do not automatically apply to people outside the stated eligibility description or to outcomes not assessed by the primary endpoint.

3. Trial Design

This was a Phase 2 randomized trial with three parallel groups: GR-MD-02 at 2 mg/kg lean body mass, GR-MD-02 at 8 mg/kg lean body mass, and placebo. The study description gives a 1:1:1 assignment ratio. The registry identifies the masking as quadruple and describes the study as double-blind; further details about which roles were masked are not reported in the registry record.

Each assignment involved infusions every other week over a 52 week period, for a total of 26 infusions. HVPG, liver biopsy, and endoscopic assessment were planned before the first infusion and after the final infusion. The description also lists liver stiffness assessment and a methacetin breath test at specified study visits if available. These additional assessments correspond to some of the secondary outcomes.

The registry lists 162 participants enrolled. For the primary outcome, the posted arm summaries include 48 participants in the 2 mg/kg group, 45 in the 8 mg/kg group, and 50 in the placebo group. The primary analysis description says it used a Full Analysis Set (FAS) and that the number analyzed was less than the participant numbers. The FAS criteria are said to be specified in the Statistical Analysis Plan, but those criteria are not reported in the registry record.

The study is marked completed. Its primary completion date is 2017-10 and its start date is 2015-06. The registry lists seven outcome measures and posts results for six secondary outcomes. Details such as the original sample-size justification, the planned handling of missing observations, and any interim analyses are not reported in the registry record.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis is performed with the Full Analysis Set (FAS) in accordance with the Protocol and the Statistical Analysis Plan (SAP). The criteria for the Full Analysis Set is specified in the SAP and resulted in the Overall Number of Participants Analyzed being less than the numbers in the Participant Flow module.

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 Change in Portal Pressure at Year 1 (Change in HVPG From Baseline and 1 Year), measured over 1 year.

The primary endpoint is change in HVPG from baseline to one year, measured in mm HG. HVPG is a measure of the pressure difference associated with blood flow through the liver and is used in this trial as a measure of portal pressure. The endpoint therefore focuses on a physiological feature of portal hypertension rather than directly counting clinical complications.

Change from baseline compares a participant’s follow-up measurement with their starting measurement. Comparing changes between randomized groups can help assess whether the groups’ average trajectories differed over the study period. The registry describes the primary outcome as a baseline-adjusted change at one year and says the analysis used the FAS.

In general, baseline adjustment accounts statistically for starting measurements when estimating a follow-up group contrast. It can improve the precision of a comparison and address baseline variation, depending on the analysis model and data. The registry does not report the full model specification or the adjustment variables beyond the description of baseline adjustment.

HVPG is relevant to the study’s stated focus on portal hypertension, but a change in this measure should not be treated as interchangeable with a change in fibrosis, symptoms, or clinical complications. Those outcomes are distinct and some are listed as secondary measures. The primary endpoint captures the registry’s principal one-year comparison; it does not alone establish the pattern of results across all outcomes or the longer-term course of the condition.

7. Results Posted in the Registry

• 2 mg/kg GR MD 02: mean -0.39 versus 0.19 on control; difference -0.58 (95% CI -2.03 to 0.87), standardized effect d = -0.16; z-test p = 0.433.
• 8 mg/kg GR MD 02: mean -0.24 versus 0.19 on control; difference -0.43 (95% CI -1.71 to 0.85), standardized effect d = -0.14; z-test p = 0.509.

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.

The Baseline-adjusted Mean Change in the Collagen Proportional Area (%), CPA

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 2 mg/kg GR MD 02: mean 1.20 versus 1.30 on control; difference -0.10 (95% CI -2.99 to 2.79), standardized effect d = -0.01; z-test p = 0.946.
  • 8 mg/kg GR MD 02: mean 0.10 versus 1.30 on control; difference -1.20 (95% CI -4.16 to 1.76), standardized effect d = -0.17; z-test p = 0.428.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 2 mg/kg GR MD 02 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 8 mg/kg GR MD 02 and the control. The interval gives the range of effects that remain compatible with the data.

The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Ishak Assessment From Liver Biology Histopathology. Histopathological Staging 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:
  • 2 mg/kg GR MD 02: 31.5% (17/54) versus 25.9% (14/54) on control; risk difference 5.6 percentage points (95% CI -11.5 to 22.6), risk ratio 1.21 (0.67–2.21); unadjusted two-proportion z-test p = 0.523.
  • 8 mg/kg GR MD 02: 24.1% (13/54) versus 25.9% (14/54) on control; risk difference -1.9 percentage points (95% CI -18.2 to 14.5), risk ratio 0.93 (0.48–1.79); unadjusted two-proportion z-test p = 0.824.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 2 mg/kg GR MD 02 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 8 mg/kg GR MD 02 and the control. The interval gives the range of effects that remain compatible with the data.

The Baseline-adjusted Mean Change in Liver Stiffness

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 2 mg/kg GR MD 02: mean -0.59 versus -0.79 on control; difference 0.20 (95% CI -0.56 to 0.96), standardized effect d = 0.10; z-test p = 0.605.
  • 8 mg/kg GR MD 02: mean -2.76 versus -0.79 on control; difference -1.97 (95% CI -2.73 to -1.21), standardized effect d = -0.98; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 2 mg/kg GR MD 02 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 mean is statistically lower for 8 mg/kg GR MD 02 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover tissue fibrosis measures, liver stiffness, a breath test, stage changes on liver biopsy, and clinical complications. Across these different measures, the results do not form a single consistent pattern that would independently settle the primary question. Some group contrasts are closer to zero, while others are more separated, and the methods and quantities differ across outcomes.

The secondary measures provide context about other aspects of liver disease, but they are not interchangeable with the primary HVPG endpoint. Nor does a pattern in one secondary measure establish a corresponding effect on portal pressure or on clinical complications. The registry reports analyses for secondary outcomes, but the full statistical analysis plan and details needed to assess all outcome definitions and modeling choices are not reported in the registry record.

Unadjusted secondary comparisons carry less weight than a prespecified primary analysis for several reasons. A trial can examine multiple outcomes and multiple treatment comparisons; considering many results increases the chance that some appear notable through random variation. The registry lists seven outcome measures and 14 analyses. A multiplicity adjustment or a prespecified hierarchy for interpreting these tests is not reported in the registry record.

Secondary results can therefore be useful for describing the breadth and consistency of observations, and for informing further research, but they should not be treated as independent confirmation solely because one comparison appears more favorable. The primary endpoint remains the principal result for the question the trial was designed to address, while secondary analyses are best viewed as supportive and exploratory unless their place in the analysis plan is clear.

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

• The Baseline-adjusted Mean Change in the Collagen Proportional Area (%), CPA
• The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Ishak Assessment From Liver Biology Histopathology. Histopathological Staging of Fibrosis
• The Baseline-adjusted Mean Change in Liver Stiffness
• The Baseline-adjusted Mean Change in Methacetin Breath Test (MBT), Measured in Percentage
• The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Brunt-Kleiner Assessment on Liver Biopsy Histopathological Staging of Fibrosis
• The Number (Percentage) of Subjects That Develop a Clinical Complication of Cirrhosis

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports ANCOVA as the method for its primary comparisons. The additional mean differences and confidence intervals discussed in the statistical summaries are simple unadjusted re-calculations from the posted group means and standard deviations. They are not substitutes for the registry’s adjusted analysis.

What does a mean change describe?

HVPG is a continuous measurement, so a mean summarizes the average change within each group. The standard deviation describes how spread out individual measurements are around that group average. A mean is useful for describing the group, but it does not show every participant’s result or the full shape of the data.

A mean difference compares two group means. For the primary comparisons, the reference group is placebo. A negative mean difference means the treatment-group mean change is numerically lower than the placebo mean change. The sign alone does not determine whether the difference is clinically important, nor does it indicate the reason for the observed pattern.

What does ANCOVA do?

In general, analysis of covariance (ANCOVA) estimates a group contrast while accounting for one or more covariates. In this trial, the registry describes a baseline-adjusted primary analysis. Adjustment can make an analysis more precise when baseline values are informative, but the estimate depends on the model specification and the data included. The registry record does not provide the model’s full covariate list, diagnostics, or adjusted effect estimates and confidence intervals.

The posted re-calculations compare group summary statistics without that baseline adjustment. They are therefore useful as transparent, approximate unadjusted comparisons, but they may differ from the sponsor’s ANCOVA results. The primary registry p-values and the unadjusted re-calculations answer related but not identical statistical questions.

How should a p-value be read?

In general, a p-value measures how compatible the observed data are with a specified null hypothesis, under the assumptions of the analysis. A larger p-value does not prove that groups are identical, and a smaller p-value does not quantify the size or importance of a difference. Interpretation should consider the estimate, its confidence interval, the design, and the analysis plan as well as the p-value.

The unadjusted primary p-values are 0.433 and 0.509. The registry’s ANCOVA p-values are 1.000 for both comparisons. Since the registry does not post adjusted estimates or confidence intervals, those p-values cannot by themselves show the range of adjusted effects compatible with the results.

What do the confidence intervals add?

In general, a confidence interval expresses uncertainty around an estimated effect under the assumptions of the calculation. A wide interval indicates less precision than a narrow interval. An interval that includes zero is compatible with no mean difference as well as with differences in either direction, at the confidence level used. The recalculated primary intervals include zero; the registry does not report confidence intervals for its ANCOVA estimates.

The posted secondary outcomes include continuous outcomes and a count outcome. Continuous outcomes are summarized with group means and standard deviations, and comparisons are expressed as mean differences. For the Ishak outcome, the posted values count participants with at least a one-stage change. In general, a difference in counts or proportions addresses a different statistical quantity from a difference in continuous means.

Some registry-reported secondary analyses also use ANCOVA. Where the posted re-calculations use unadjusted comparisons, the same distinction applies: they do not reproduce baseline-adjusted model results. The statistical method used for each comparison, the outcome definition, and the analysis population should be considered together rather than treating all reported values as interchangeable.

11. Confidence Intervals and Precision

Precision is about how narrowly the data locate an estimated group difference. The recalculated primary confidence intervals extend across zero, so the results remain compatible with no mean difference as well as with effects in either direction. The intervals are not narrow enough to establish that the two dose groups and placebo had the same mean change.

The two primary unadjusted mean differences are -0.58 mm HG and -0.43 mm HG. Their p-values, 0.433 and 0.509, are consistent with considerable uncertainty in these comparisons. Neither p-value tells readers how large the adjusted difference is; the registry’s ANCOVA estimates and confidence intervals are not reported in the registry record.

Confidence intervals are useful because they show a range of estimates compatible with the data and the calculation assumptions, rather than reducing the evidence to a single p-value. In general, the interval does not mean there is a specified probability that the fixed effect lies inside its endpoints. Its interpretation relies on the statistical procedure and model assumptions.

For the primary outcome, the posted group sizes used in the unadjusted comparison are 48, 45, and 50. Those numbers, together with variability in the measurements, affect precision. The registry’s FAS description notes that the analysis included fewer participants than the participant numbers, but does not provide enough detail to evaluate the consequences of that difference. The confidence intervals are unadjusted re-calculations and should not be mistaken for intervals from the sponsor’s ANCOVA.

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 values are participants per arm, not total events. The trial’s sample-size design assumptions are not reported in the registry record. The displayed planning illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the observed effect as a starting point and show planning for 100%, 75%, or 50% of that observed effect.

The 80% power column gives the planned number of participants per arm under those assumptions for an analysis to have an 80% probability of detecting the specified effect if that effect is the true one. The 90% power column gives the corresponding number for a 90% probability. These are prospective planning quantities, not probabilities that the observed trial result is correct.

Smaller target effects require more participants to distinguish them from random variation under the same assumptions. This is why planning for 75% or 50% of an observed effect generally requires more participants per arm than planning for the full observed effect. When an observed effect is small relative to the variability, the resulting planning counts can be very large; such values should be read as illustrations of the assumptions, not as recommendations for a future study.

The curve can be read as a visual representation of how estimated power changes as the planned sample size or target effect changes, subject to the stated assumptions. The planning figures are based on the observed results, so they are not observed power.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.580; pooled standard deviation σ = 3.642.
2. n = 2 × (1.96 + 0.842)² × 3.642² / -0.580² = 618.9, rounded up to 619 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
delta <- -0.58                      # observed difference in means
sigma <- 3.64172238897109                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2462967)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 619 (80% power), 829 (90% power)
 75% of observed effect: n per arm = 1,101 (80% power), 1,473 (90% power)
 50% of observed effect: n per arm = 2,476 (80% power), 3,314 (90% power)
power.t.test: 619.8 
Simulated power at n = 619 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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

For the primary endpoint, the registry reports sponsor analyses using ANCOVA, with p-values of 1.000 for the 2 mg/kg comparison and 1.000 for the 8 mg/kg comparison. The registry does not report the corresponding adjusted effect estimates or confidence intervals. The sponsor’s reported analysis is the trial’s own model-based result and should be kept distinct from the unadjusted re-calculations.

The recalculated primary mean differences use the posted means and standard deviations and do not adjust for baseline values. They produce p-values of 0.433 and 0.509 and confidence intervals that include zero. Differences between these and the registry’s ANCOVA p-values can arise because the methods, adjustment, or analyzed data may differ; the available record does not show enough detail to identify the reason in this case.

Accordingly, the re-calculations are a descriptive cross-check, not a replacement for the prespecified analysis. They should not be used to infer the adjusted effect from the sponsor’s model. Since the record does not provide the adjusted estimates, readers cannot compare the magnitudes and precision of the two analyses directly.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and 14 analyses, including comparisons of each GR-MD-02 dose with placebo. Testing multiple outcomes and comparisons creates a multiplicity concern: in general, the more statistical tests considered, the greater the chance of observing a seemingly notable result by chance. A planned adjustment, testing hierarchy, or other multiplicity strategy is not reported in the registry record. It is therefore not possible to determine from the record whether or how the reported secondary tests were protected against this issue.

The primary outcome description says the analysis used the Full Analysis Set and that the number analyzed was less than the participant numbers. It also says the criteria for inclusion in that set are specified in the Statistical Analysis Plan. The actual criteria and the reasons for participants not appearing in the analyzed group are not reported in the registry record.

Missing-data methods are not reported in the registry record. The record does not explain how missing primary or secondary measurements were handled, whether any sensitivity analyses were conducted, or how withdrawals and incomplete follow-up affected the analyses. These details matter because analysis of only participants with available measurements can be biased if the availability of measurements is related to outcome or treatment assignment.

The registry notes ANCOVA for reported analyses, but complete model specifications and diagnostics are not reported. Interim analyses and any associated stopping rules are also not reported in the registry record. These gaps limit assessment of the statistical plan and of how robust the posted findings are to analysis choices; they do not by themselves demonstrate that the analyses were inappropriate.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (3.8%), sepsis (3.7%), supraventricular tachycardia (3.7%), anaemia (3.7%), haematemesis (1.9%).

The registry reports participants at risk and participants affected by serious adverse events for each group. Serious adverse events affected 10 of 53 participants in the 2 mg/kg group, 16 of 54 in the 8 mg/kg group, and 12 of 54 in the placebo group. These are counts of participants, not counts of all separate event episodes.

The record reports one death in the 2 mg/kg group and no deaths in the 8 mg/kg or placebo groups. It also lists serious adverse event terms and percentages, including abdominal pain, sepsis, supraventricular tachycardia, anaemia, haematemesis, and abscess of eyelid. The listed terms are not presented by treatment group in the registry record.

These descriptive figures do not establish that an event was caused by a study assignment, and they do not by themselves support a comparison of safety between groups. The registry record does not provide enough information about event timing, severity detail, follow-up completeness, or attribution to treatment to resolve those questions. Serious adverse event counts should be read separately from the primary efficacy endpoint and from the broader counts of participants affected by other adverse events.

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

The posted results describe one-year changes in HVPG for three randomized groups and provide an unadjusted comparison of each dose with placebo. The unadjusted mean differences are -0.58 mm HG for 2 mg/kg and -0.43 mm HG for 8 mg/kg. Their confidence intervals include zero, while the registry’s own ANCOVA analyses report p-values of 1.000 for both dose comparisons.

These findings do not establish a clear between-group difference in the primary endpoint. They also do not establish equivalence or rule out potentially relevant differences, because the confidence intervals do not exclude effects in either direction. The adjusted ANCOVA estimates and intervals are not reported, which limits interpretation of the sponsor’s model-based results.

The result is specific to the trial’s selected population, the study assignments, and the one-year HVPG endpoint. It does not directly answer whether there were differences in fibrosis, liver stiffness, clinical complications, or other outcomes, even though some were assessed as secondary measures. It also does not establish longer-term effects beyond the reported timeframe.

General statistical interpretation requires considering effect estimates, uncertainty, analysis methods, and the study’s conduct together. The posted information leaves important details about the FAS criteria, missing data, multiplicity, and adjusted estimates unresolved. These limits make it inappropriate to treat a single p-value or group mean as a definitive summary of all possible effects.

Nothing in these results alone should be interpreted as medical advice or as a determination of treatment suitability. They are statistical descriptions of the outcomes recorded for this trial and do not replace a full appraisal of the protocol, analysis plan, and complete clinical evidence.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison cannot be reduced to a ranking of group means. The arm averages point in different numerical directions for the primary change measure, but the unadjusted comparisons are uncertain, and the registry’s adjusted analyses are reported only as p-values. Without adjusted estimates and confidence intervals, the model-based results cannot be interpreted in terms of effect size and precision.

It also shows why analysis populations matter. The registry identifies a Full Analysis Set for the primary endpoint, yet says fewer participants were analyzed than the participant numbers and does not report the FAS criteria. Readers need to know which participants contributed data and how missing measurements were treated to assess the meaning of the estimates.

The trial includes multiple outcomes and comparisons, including continuous measurements and stage-change counts. These outcomes address related but distinct questions. Without a reported multiplicity plan, selective emphasis on an individual secondary result risks overstating what the collection of tests establishes.

Finally, planning figures based on observed effects can demonstrate how sample-size needs change with the effect a future study aims to detect, but they do not explain the original design. The trial’s initial sample-size justification is not reported in the registry record. Keeping planning illustrations, observed estimates, and the original trial design distinct is essential to sound statistical interpretation.

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 outcome includes group summaries and unadjusted re-calculations, but the registry’s ANCOVA estimates and confidence intervals are not reported. This prevents direct assessment of the size and precision of the sponsor’s adjusted contrasts. The record also does not provide full model details or diagnostics, so the exact assumptions underlying the reported analyses cannot be evaluated.

The FAS is described but its membership criteria are not. The primary analysis used fewer participants than the participant numbers, and the reasons for this are not reported in the registry record. Missing-data handling, sensitivity analyses, and the effect of incomplete follow-up are also not reported. These omissions matter for interpreting both the estimates and their generalizability.

The registry describes a narrowly defined population with cirrhosis and portal hypertension, and excludes participants with medium or large varices and decompensated cirrhosis. The findings therefore pertain to the stated eligibility group; the record does not support extending them to people outside it without additional evidence.

The record lists multiple outcomes and analyses but does not report a multiplicity strategy. It also does not report the original sample-size justification, interim analyses, or a detailed hierarchy among endpoints. Secondary results should consequently be interpreted cautiously, particularly when considering isolated comparisons.

Finally, the primary endpoint is a one-year pressure measurement. It is not a direct measure of every clinical outcome of interest, and the listed secondary outcomes do not fill every possible evidence gap. The registry record does not report longer-term outcome results beyond the stated study timeframes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients With Nash Cirrhosis — NCT02462967.
• Registry record last updated 2020-10-08; status last verified 2020-10.
• Results first posted 2020-10-08.
• 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

NCT02462967 is a completed randomized Phase 2 trial of GR-MD-02 in participants with NASH cirrhosis and portal hypertension. The trial assigned participants to 2 mg/kg GR-MD-02, 8 mg/kg GR-MD-02, or placebo, administered every other week over a 52 week period.

The primary outcome was change in HVPG from baseline at one year. The unadjusted mean differences versus placebo were -0.58 mm HG and -0.43 mm HG; both recalculated confidence intervals include zero. The registry reports ANCOVA p-values of 1.000 for both comparisons but does not report the adjusted estimates or intervals.

The registry also posts secondary outcomes and serious adverse event counts. Interpretation is limited by unreported details about the FAS criteria, missing-data methods, multiplicity, and the sponsor’s adjusted effect estimates.