Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Adults With Idiopathic Pulmonary Fibrosis (IPF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Adults With Idiopathic Pulmonary Fibrosis (IPF) (NCT01769196), a randomized phase 2 study. The primary outcome is Progression Free Survival.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter, parallel-group trial sponsored by Gilead Sciences. The registry lists enrollment of 544 and the study status as terminated. The recorded study start was 2013-01-31, and primary completion was 2016-02-23. The reason for termination is not reported in the registry record.

Participants were allocated to simtuzumab or simtuzumab placebo. The primary outcome analysis used the ITT Analysis Set. The posted primary outcome includes 272 participants in each arm. The registry describes treatment for up to 254 weeks in both groups. The primary endpoint timeframe is listed as up to 148 weeks; the overall survival secondary outcome timeframe is up to 151 weeks.

Randomization and double masking are important design features for interpreting a treatment comparison. In general, random assignment aims to balance measured and unmeasured characteristics between groups, while masking can reduce differences in care or outcome assessment that might otherwise affect results. These features support a comparative interpretation, but they do not remove uncertainty from the observed estimates or establish that all possible sources of bias were controlled.

The registry record does not report the allocation sequence method, the details of who was masked, the reason the trial was terminated, or the original statistical design assumptions. It also does not report details of interim analyses. These matters should not be inferred from the trial’s phase, status, or posted results.

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.

Before assignment: 1250 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT 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.

Population: Intent-to-Treat (ITT) Analysis Set included all participants who were randomized into the study, and were analyzed according to treatment randomized.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival, measured over Up to 148 weeks.

The primary endpoint was progression-free survival (PFS), reported as median time in months. The registry defines a PFS event as a categorical decline in FVC % predicted: at least a 10% relative decrease in FVC and at least a 5% absolute decrease from baseline, confirmed at a consecutive visit at least 2 weeks later using the same criteria. The study objectives also describe PFS as determined by either this categorical FVC decline or all-cause mortality.

FVC is a measure of the amount of air that can be forcibly exhaled after a full breath. In general, a time-to-event endpoint combines information about whether and when a defined event occurs, rather than considering only a measurement at a single visit. It can therefore reflect the timing of progression or death during follow-up. The confirmation requirement in the registry definition makes the specified FVC decline dependent on a subsequent qualifying visit, rather than a single measurement alone.

PFS is used in this study to assess the time until a clinically defined progression event or death. The record lists the primary outcome timeframe as up to 148 weeks. It does not report further details on how deaths, missed visits, or other incomplete observations were handled in the endpoint analysis.

7. Results Posted in the Registry

• Simtuzumab vs Simtuzumab Placebo: hazard ratio 1.13 (95% CI 0.88–1.45), reported p = 0.329 (as reported in the registry).

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.

Overall Survival (OS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Simtuzumab vs Simtuzumab Placebo: hazard ratio 1.20 (95% CI 0.61–2.37), reported p = 0.602 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Simtuzumab vs Simtuzumab Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Overall Survival Among the Participants With sLOXL2 ≥ 50th Percentile

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Simtuzumab vs Simtuzumab Placebo: hazard ratio 0.99 (95% CI 0.43–2.28), reported p = 0.988 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Simtuzumab vs Simtuzumab Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Overall Survival Among the Participants With sLOXL2 ≥ 75th Percentile

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Simtuzumab vs Simtuzumab Placebo: hazard ratio 0.95 (95% CI 0.30–2.99), reported p = 0.925 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Simtuzumab vs Simtuzumab Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results include overall survival in the full analysis group and in sLOXL2-defined subgroups. Across these reported comparisons, the hazard-ratio estimates are close to 1 or lie on either side of it, and all reported 95% confidence intervals include 1. The intervals are broad, particularly for the subgroup comparisons, so these secondary estimates do not provide a precise picture of the treatment comparison.

These results complement but do not replace the primary PFS analysis. Overall survival is a distinct endpoint from PFS: the primary endpoint uses a defined FVC decline or death, whereas overall survival concerns death. Agreement or disagreement between these endpoints cannot be assumed, and a secondary outcome does not overturn the primary result on its own. The registry also lists secondary measures involving FVC, walking distance, respiratory hospitalizations, exacerbations, and respiratory deaths, but numerical effect estimates for the remaining measures are not reported in the registry record.

In general, secondary outcomes help describe different aspects of a trial, but multiple outcome tests create more opportunities for chance findings. Unless an analysis plan specifies how multiplicity is controlled, an isolated secondary p-value should be treated cautiously. The registry entries do not report a multiplicity adjustment or a hierarchy for interpreting these secondary tests. The subgroup analyses also use narrower populations than the overall comparison and may have less information, which contributes to their uncertainty.

The secondary evidence therefore offers context rather than a separate definitive conclusion. Its uncertainty, the distinct outcome definitions, and the absence of reported multiplicity procedures limit how strongly it can be used to support a broad claim about treatment effects across outcomes.

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

• Overall Survival (OS)
• Overall Survival Among the Participants With sLOXL2 ≥ 50th Percentile
• Overall Survival Among the Participants With sLOXL2 ≥ 75th Percentile
• Relative Change From Baseline in FVC % Predicted
• Definite Acute Exacerbations of IPF Among Adjudicated Respiratory Hospitalizations
• Number of Adjudicated Respiratory Hospitalizations (ARP) Among Total Hospitalizations
• Number of Participants Experiencing Adjudicated Respiratory Deaths Among Those With Adjudicated Death
• Absolute Change From Baseline in 6 Minute Walk Distance (6MWD)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis is a time-to-event comparison. In general, a time-to-event analysis considers both whether an event occurred and the time until it occurred. Participants who have not had an event by the end of their observed follow-up may contribute information up to that point, depending on the analysis rules. The registry identifies the primary measure as median PFS and reports a log-rank hazard ratio. It does not give the detailed censoring rules or the handling of missing endpoint assessments.

What does the median describe?

In general, the median event time is the point at which the estimated proportion remaining event-free reaches one half. It is a summary of the estimated event-time distribution, not the arithmetic mean of individual follow-up times. A median can be difficult to estimate precisely when relatively few observed participants reach the event threshold during follow-up. The registry reports median PFS values of 12.6 months for simtuzumab and 15.4 months for placebo, with 95% confidence intervals of 11.3 to 14.4 months and 12.6 to 19.1 months, respectively.

The median is only one feature of the time-to-event pattern. Two groups can have similar medians but different patterns at other times, or different medians while their uncertainty remains substantial. The registry’s reported hazard ratio provides another summary, drawing on the comparison over follow-up rather than only the median point. It should be read together with its confidence interval and the method named in the record.

How should the hazard ratio be read?

In general, a hazard ratio compares the instantaneous event rates between groups among participants still at risk at a given time. A value of 1 represents equal hazards under the model’s interpretation. Values above or below 1 indicate a relative direction for the comparison, but a hazard ratio is not a risk difference, an absolute probability, or a ratio of median times. The reported primary hazard ratio of 1.13 is for simtuzumab versus simtuzumab placebo. Its 95% confidence interval, 0.88 to 1.45, includes 1, so the data are compatible with a range including no relative hazard difference.

The registry names the log-rank method for the primary comparison and reports p = 0.329. In general, the log-rank test compares event-time experience across groups while accounting for the order and timing of events. A p-value describes how unusual the observed test result would be under a specified null model and its assumptions; it is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of an effect. The registry record does not provide additional details on model diagnostics or assumptions beyond the method and reported estimate.

What does the confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity under the statistical procedure used. A narrower interval indicates greater precision for that estimate, while a wider interval allows a broader set of plausible values. The primary hazard-ratio interval runs from 0.88 to 1.45. Because it spans 1, the estimate does not distinguish a relative hazard below 1 from one above 1 at the interval’s stated confidence level. This is not proof that the groups are identical; it reflects uncertainty in the estimated comparison.

The primary outcome is defined using a categorical FVC decline with confirmation at a consecutive visit at least 2 weeks later, or all-cause mortality as described in the study objective. In general, an event definition affects which observations count as events and when events are dated. A confirmation rule can reduce reliance on a single measurement, but it can also make the timing and availability of follow-up assessments relevant. The registry entries do not specify further adjudication or event-date rules for the primary analysis.

Why can event-time results be difficult to interpret?

In general, time-to-event methods rely on assumptions about how follow-up and censoring relate to the event. If participants leave observation or have incomplete follow-up, the analysis needs rules for how to use their available information. The registry record does not report the reasons for censoring, missing-data procedures, or sensitivity analyses, so those choices cannot be assessed from the reported details.

Hazard ratios are often interpreted as a relative comparison over time, but a single hazard ratio can be less representative if the relative hazards change during follow-up. Whether proportional hazards were assessed, and what diagnostics were used, are not reported in the registry record. The log-rank method and hazard ratio are the reported approach; no unreported assumptions or checks should be inferred.

The overall survival secondary analyses also use log-rank hazard ratios. In general, subgroup comparisons are less precise when based on fewer observations or events, and subgroup findings can be particularly sensitive to multiplicity and selection. The registry lists sLOXL2-based categories for overall survival, but the registry entries do not provide an interaction test establishing that the treatment comparison differs across those categories. Subgroup estimates should therefore be viewed as estimates for those defined groups, not proof of a distinct treatment effect.

11. Confidence Intervals and Precision

Precision concerns how tightly the data estimate an effect. The primary median PFS estimate for simtuzumab is 12.6 months, with a 95% confidence interval from 11.3 to 14.4 months. For placebo, the median is 15.4 months, with a 95% confidence interval from 12.6 to 19.1 months. The reported hazard ratio is 1.13, and its 95% confidence interval is 0.88 to 1.45. These intervals communicate uncertainty; they are not ranges containing every participant’s outcome.

In general, a 95% confidence interval is generated by a method that, under its assumptions and repeated use, would cover the true parameter in 95% of such intervals. It is not a statement that there is a 95% probability that the true value lies in this particular interval. Wider intervals indicate less precision, and narrow intervals indicate greater precision, without by themselves indicating whether an effect is important.

The hazard-ratio interval includes 1, the value corresponding to equal hazards. It also permits values below and above 1, so the comparative estimate remains uncertain in direction and magnitude. The p-value of 0.329 is consistent with the interval’s failure to exclude 1 under the reported analysis, but it does not quantify the probability that simtuzumab is effective or ineffective.

Overall survival estimates are less precise: the overall-group hazard ratio is 1.20 with a 95% confidence interval from 0.61 to 2.37; the estimate for participants at or above the sLOXL2 50th percentile is 0.99 with a 95% confidence interval from 0.43 to 2.28; and the estimate for participants at or above the 75th percentile is 0.95 with a 95% confidence interval from 0.30 to 2.99. Each interval includes 1 and spans a broad range. Median overall survival estimates are not reported in the registry record.

Precision is affected by the amount and distribution of information available for an endpoint, including the number and timing of events. The registry entries do not report the event counts used in these analyses, so precision should be judged from the estimates and their intervals rather than inferred from enrollment alone.

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 figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. For the time-to-event outcomes, the entries are total event targets, not participants per arm. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect, and the time-to-event event calculations use the Schoenfeld approach. The original trial’s own sample-size justification and design assumptions are not reported in the registry record.

The 80% power column represents a planning target under which a study would have an 80% chance of detecting the specified effect if that effect and the planning assumptions were correct. The 90% power column uses a higher target probability of detecting that effect. These are design concepts, not guarantees about the result of a future study. This is not observed power.

The entries compare planning for 100%, 75%, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so the planning illustration requires more events to target the same power. For example, the primary comparison’s event target increases across those effect assumptions in both the 80% and 90% columns. The figures are conditional on the stated assumptions and should not be read as enrollment recommendations, since the record does not give a conversion from event targets to a required follow-up duration or participant count.

For overall survival and the LOXL2-defined overall survival subgroups, the same interpretation applies: the figures are total event targets for planning under the stated effect fractions. They are not observed events and do not describe the number of participants enrolled in the trial. They also do not show that the trial had a particular probability of detecting its observed result.

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

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.130, so ln(HR) = 0.1222.
2. d = 4 × (1.96 + 0.842)² / [ln(1.130)]² = 2,101.8, rounded up to 2,102 events in total 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
hr <- 1.13                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(1769196)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 2,102 (80% power), 2,814 (90% power)
 75% of observed effect: events = 3,737 (80% power), 5,003 (90% power)
 50% of observed effect: events = 8,408 (80% power), 11,256 (90% power)
Simulated power with 2,102 events: 0.805 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis is a log-rank comparison with a hazard ratio of 1.13, a 95% confidence interval from 0.88 to 1.45, and p = 0.329. The posted primary estimate is consistent with that reported analysis. No discrepancy is identified between the sponsor’s reported primary result and the presented recalculation.

The sponsor’s own analysis is the primary source for interpreting the trial result. Recalculated values, when displayed, are simple unadjusted calculations from posted summary statistics and may not reproduce all details of the sponsor’s analysis. In this case, the reported hazard ratio, interval, method, and p-value are the values to use when describing the sponsor’s inferential result.

The registry does not report enough detail in the registry record to reconstruct the full individual-level analysis or establish whether other covariate adjustments or additional analyses were performed. The recalculation should therefore be understood as a check based on posted summaries, not as a replacement for the trial’s reported analysis. Planning illustrations derived from the observed effect are also separate from the sponsor’s original trial-design calculations, which are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The primary outcome is identified as PFS in the ITT Analysis Set. The study objectives also refer to evaluating PFS in participants classified as LOXL2 high at baseline. The registry lists several secondary outcomes, including overall survival in the full group and in sLOXL2-defined subgroups, as well as measures of FVC, walking distance, respiratory hospitalizations, exacerbations, and respiratory deaths.

When many outcomes or subgroups are tested, the chance of obtaining at least one apparently unusual result can increase. In general, multiplicity procedures can control that risk by adjusting significance thresholds or by specifying a hierarchy for testing. Whether such procedures were used for this trial is not reported in the registry record. No conclusion about adjustment, prespecification of every secondary comparison, or a formal testing sequence can be drawn from the listed outcome names alone.

The registry describes the LOXL2 level used to classify the high subgroup as prespecified in the primary objectives, but it does not report the complete subgroup analysis plan or an interaction test. The overall survival results for the sLOXL2 percentile subgroups should therefore be interpreted as subgroup estimates with substantial uncertainty, not as evidence that the treatment effect differs by LOXL2 level.

The primary analysis population is reported as ITT. The registry entries do not describe other analysis populations, such as a per-protocol or safety population definition for efficacy analyses. They also do not report methods for missing outcome data, censoring, protocol deviations, or sensitivity analyses. Those omissions limit assessment of how robust the results are to incomplete follow-up and analysis choices. These details should be regarded as not reported in the registry record, rather than assumed to follow a particular standard procedure.

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: idiopathic pulmonary fibrosis (12.9%), pneumonia (6.6%), dyspnoea (3.7%), atrial fibrillation (2.2%), acute respiratory failure (2.2%).

The registry reports serious adverse events affecting 101 of 271 participants at risk in the simtuzumab group and 97 of 272 at risk in the placebo group. Other adverse events affected 237 of 271 participants at risk with simtuzumab and 246 of 272 at risk with placebo. Deaths were reported for 31 participants in the simtuzumab group and 32 in the placebo group. These are the recorded counts and denominators; they are not adjusted comparisons.

The most frequently listed serious adverse event terms include idiopathic pulmonary fibrosis (12.9%), pneumonia (6.6%), dyspnoea (3.7%), atrial fibrillation (2.2%), acute respiratory failure (2.2%), and respiratory failure (1.8%). These percentages describe the registry’s listed terms and should not be added together, since the record does not establish that event categories are mutually exclusive.

In general, adverse-event counts describe events recorded under the study’s reporting definitions; they do not by themselves establish that the treatment caused an event. The registry entries do not provide additional detail on event duration, severity grading, exposure-adjusted rates, or the method used to assess causality. These safety counts should be read alongside the study’s efficacy findings and the limits of the reported safety information, without treating raw group counts as proof of a difference.

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

The posted primary result describes the PFS comparison observed in the randomized, double-blind, placebo-controlled study. The median PFS was 12.6 months with simtuzumab and 15.4 months with placebo. The reported hazard ratio was 1.13, with a 95% confidence interval from 0.88 to 1.45 and p = 0.329. The interval includes 1 and allows a range of relative comparisons, so the estimate is not sufficiently precise to establish a clear difference in either direction.

This does not mean the groups have been shown to be identical. A non-significant p-value is not proof of no effect, and the confidence interval indicates that uncertainty remains. Nor does the point estimate alone establish a clinically important effect. The posted analysis gives an estimate and its uncertainty under the reported method, not a definitive answer to every possible treatment question.

The result applies to the endpoint definition, analysis population, and follow-up described in the registry. It does not automatically establish effects on overall survival, other measures of lung function, symptoms, or outcomes in subgroups. The secondary overall survival estimates are also imprecise, and numerical results for several other listed secondary outcomes are not reported in the registry record.

The registry marks the study as terminated, but the reason is not reported in the registry record. Termination status alone does not establish why the study ended or how that decision affected the analysis. Details about missing-data handling, multiplicity, and other statistical procedures are also not reported, which constrains a fuller assessment of robustness.

Accordingly, the results support a cautious description of the observed comparison and its uncertainty. They do not, on their own, warrant a general conclusion about treatment effects beyond the population, outcomes, and analyses recorded in this trial.

18. Why This Trial Matters Statistically

This trial is statistically informative because it uses a randomized, double-blind, placebo-controlled design to compare simtuzumab with placebo on a time-to-event primary endpoint. Randomization and masking are features intended to strengthen a comparative evaluation. The primary endpoint also combines a defined lung-function progression criterion with the study objective’s consideration of all-cause mortality, rather than relying only on a single measurement at one visit.

The result illustrates why a point estimate should not be read without its uncertainty. The primary hazard ratio is 1.13, but its 95% confidence interval extends from 0.88 to 1.45. The interval includes the value corresponding to equal hazards and spans estimates on either side. The median PFS values also need to be interpreted as time-to-event summaries, not as a complete account of the event-time pattern.

The trial further shows the distinction between an endpoint result and a broader evidence claim. Secondary overall survival estimates include subgroup comparisons, but their confidence intervals are broad, and the registry does not report multiplicity procedures or a full subgroup analysis plan. The record lists other secondary outcomes without numerical results in the registry record for this analysis. These features matter when judging how much weight to give findings beyond the primary comparison.

Finally, the registry’s planning illustrations emphasize that power calculations depend on assumptions about the effect to detect and the amount of event information required. They are not observed power and do not replace the original design justification, which is not reported in the registry record. Together, the study’s estimates and reporting limits provide a useful example of why effect size, precision, endpoint definition, and analysis transparency must be considered together.

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 primary result is based on the registry’s stated PFS definition and ITT Analysis Set, but the registry entries do not include detailed rules for censoring, missing measurements, or incomplete follow-up. The FVC component requires confirmation at a consecutive visit at least 2 weeks later, making follow-up assessments relevant to determining whether the criterion was met. The registry does not provide further detail on event adjudication or the handling of participants without confirmation.

The study status is terminated, and the reason for termination is not reported in the registry record. The record also does not give the original sample-size justification, interim-analysis details, or complete statistical analysis plan. As a result, the relationship between the observed information and the trial’s original design targets cannot be assessed from these registry entries.

The primary objective mentions a LOXL2-high subset, but a corresponding primary PFS estimate for that subset is not reported in the registry entries. The secondary overall survival subgroup estimates have broad confidence intervals, and the record does not report an interaction test. Multiplicity handling for the many listed endpoints and subgroup analyses is not reported.

Numerical results for several listed secondary outcomes are not reported in the registry record. Median overall survival values are also not reported, despite the posted hazard-ratio comparisons. The safety information includes participant counts and listed serious adverse event terms, but the registry entries do not report exposure-adjusted rates or additional event-level context. These limitations restrict detailed assessment and counsel against extending conclusions beyond the reported endpoints and analyses.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Adults With Idiopathic Pulmonary Fibrosis (IPF) — NCT01769196.
• Registry record last updated 2017-05-30; status last verified 2017-04.
• Results first posted 2017-04-13.
• 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

The registry record describes a Phase 2 randomized, double-blind, placebo-controlled, multicenter, parallel-group study of simtuzumab in adults with idiopathic pulmonary fibrosis. Enrollment was 544, and the recorded status is terminated. The primary endpoint was PFS, defined using a confirmed categorical FVC decline or all-cause mortality as described in the study objective.

Median PFS was 12.6 months with simtuzumab and 15.4 months with placebo. The reported log-rank hazard ratio was 1.13, with a 95% confidence interval from 0.88 to 1.45 and p = 0.329. The interval includes 1 and indicates uncertainty in the comparative estimate.

Secondary overall survival hazard-ratio estimates were imprecise, with confidence intervals including 1. Further secondary outcome values, the reason for termination, the original design assumptions, and important details of missing-data and multiplicity procedures are not reported in the registry record.