Safety, Tolerability, Pharmacokinetics, and Efficacy of JBT-101 (Lenabasum) in Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, Pharmacokinetics, and Efficacy of JBT-101 (Lenabasum) in Cystic Fibrosis (NCT02465450), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events..

2. Clinical Question

3. Trial Design

This is a phase 2, randomized, double-blind, placebo-controlled, multicenter study of JBT-101 in cystic fibrosis. The registry lists enrollment of 85 and a sequential model. The trial status is completed. The recorded start date is 2015-09-29, and the primary completion date is 2016-12-28. Corbus Pharmaceuticals Inc. is listed as the sponsor.

The study purpose was to evaluate safety, tolerability, pharmacokinetics, and efficacy of JBT-101 in adults with cystic fibrosis. The listed intervention groups include JBT-101 1 mg once daily, JBT-101 5 mg once daily, and placebo once daily on Days 1-28. The other listed regimens are JBT-101 20 mg once daily, JBT-101 20 mg twice daily, and placebo twice daily on Days 29-84. The registry identifies masking as double and allocation as randomized.

The posted primary outcome is the number of participants with treatment-emergent adverse events over 84 days of treatment. Its population description says the tabulation is based on participants who entered Treatment Period 2 (n=81) and includes all treatment-emergent adverse events. The arm-level outcome counts include denominators that vary across the listed groups. The record does not explain the relationship between these arm denominators, the Treatment Period 2 population description, and the sequential regimen structure. That detail should not be inferred from the arm labels alone.

The registry lists JBT-101 plasma concentrations on Day 84 as a secondary outcome. Although the record identifies two outcome measures, no analysis results are posted for the secondary outcome in the information summarized for this trial. A fuller description of the randomization sequence, masking procedures, and operational details is 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.

Treatment Period 1

Treatment Period 2

Analysis population for the primary outcome, as defined in the registry: These adverse events are based on subjects who entered Treatment Period 2 (n=81). The tabulation of adverse events includes all TEAEs.

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 Number of Participants With Treatment Emergent Adverse Events., measured over 84 days of treatment.

The primary endpoint counts participants who experienced treatment-emergent adverse events during 84 days of treatment. The registry says the tabulation includes all such events and is based on participants who entered Treatment Period 2 (n=81). The measure is a participant count: it records whether a participant had an event, rather than how many separate events that participant experienced. It therefore does not by itself describe the number, duration, severity, or timing of events.

Counting participants with events is useful for a safety outcome because it gives a group-level measure of how many people were affected at least once during the stated treatment period. Comparing these counts with the group denominators can describe the observed frequency across groups. The posted comparisons express the difference as a risk difference and also report uncertainty intervals and unadjusted p-values.

Interpretation depends on the endpoint definition and the population included. The registry does not give a detailed definition of treatment-emergent, or additional rules for deciding which events qualify. The endpoint also does not isolate serious events: the primary count includes all treatment-emergent adverse events, while serious adverse events are reported separately. Neither count alone establishes whether an event was caused by a study treatment. The registry record does not report an adjudication method or a causal-attribution rule.

7. Results Posted in the Registry

• JBT101 1 mg QD: 53.8% (14/26) versus 42.9% (15/35) on control; risk difference 11.0 percentage points (95% CI -14.2 to 36.2), risk ratio 1.26 (0.75–2.12); unadjusted two-proportion z-test p = 0.395.
• JBT-101 5 mg QD: 54.2% (13/24) versus 42.9% (15/35) on control; risk difference 11.3 percentage points (95% CI -14.5 to 37.1), risk ratio 1.26 (0.74–2.15); unadjusted two-proportion z-test p = 0.393.
• JBT-101 20 mg QD: 70.0% (21/30) versus 42.9% (15/35) on control; risk difference 27.1 percentage points (95% CI 4.0 to 50.3), risk ratio 1.63 (1.04–2.56); unadjusted two-proportion z-test p = 0.028.
• JBT-101 20 mg BID: 67.9% (19/28) versus 42.9% (15/35) on control; risk difference 25.0 percentage points (95% CI 1.2 to 48.8), risk ratio 1.58 (1.00–2.51); unadjusted two-proportion z-test p = 0.048.

8. Statistical Interpretation

9. Statistical Methods Explained

What is the outcome scale?

The primary outcome is binary at the participant level: each participant is counted in relation to whether a treatment-emergent adverse event occurred during 84 days of treatment. The posted arm values are counts of participants with an event, with group denominators given separately. The comparisons use a risk difference. In general, a risk difference subtracts one group’s event proportion from the other group’s event proportion. It is an absolute contrast, expressed on the same scale as the proportions, and is distinct from a relative measure such as a risk ratio or odds ratio.

The registry also posts risk ratios and odds ratios for the comparisons. In general, a risk ratio compares event proportions as a ratio, while an odds ratio compares event odds. These measures use different scales and can give a different impression of the size of a contrast. The principal comparisons discussed in the results use the risk difference, so interpretation should focus on that absolute scale rather than treating the various measures as interchangeable.

What does a confidence interval describe?

A confidence interval communicates uncertainty around an estimate. In general, a wider interval indicates less precision, and an interval that includes zero for a risk difference is compatible with no difference under the interval’s statistical assumptions. An interval that excludes zero does not, by itself, establish a causal effect or address whether multiple comparisons were considered. The interval width depends in part on the amount of information in the groups; small denominators generally leave greater uncertainty than larger ones.

The posted comparisons give confidence intervals for the risk differences. The intervals for JBT101 1 mg QD, JBT-101 5 mg QD, and placebo BID include zero. The intervals for JBT-101 20 mg QD and JBT-101 20 mg BID are above zero. These are unadjusted intervals in the posted comparisons; the registry record does not say whether any multiplicity procedure was applied. The confidence level and interval construction method are not reported in the registry record.

How should the p-values be read?

The unadjusted p-value is a measure of how incompatible the observed data are with a specified no-difference statistical model, under the assumptions used for that calculation. It is not the probability that the treatment works or that the null hypothesis is true. It also does not measure the size or clinical importance of a difference. The posted p-values are 0.395, 0.393, 0.028, 0.048, and 0.18 for the listed comparisons. The registry record does not report whether these values are sponsor analyses or what prespecified testing strategy governs their interpretation.

When several comparisons are examined, the chance of obtaining a small p-value somewhere among them can be higher than for a single comparison. General statistical practice may address this with a prespecified multiplicity strategy, such as adjustment or a hierarchy of tests. Whether such a strategy was used in this trial is not reported in the registry record. The p-values should therefore be read as posted, unadjusted comparison values, not as a complete account of confirmatory testing.

What is the role of the arm counts?

The posted event counts and denominators support the proportions and contrasts in the registry. Denominators differ across the displayed groups, and the outcome population description refers to participants entering Treatment Period 2 (n=81). The registry does not explain how the differing arm counts align with the sequential model or the outcome population statement. This makes it important not to assume that every comparison represents a simple parallel-group allocation over the entire treatment period. The original analysis population definitions and handling of participants who did not enter Treatment Period 2 are not reported in the registry record.

The primary outcome includes all treatment-emergent adverse events, while serious events appear in a separate safety listing. The participant counts for the primary outcome should not be confused with the number of individual event reports, and the serious-event figures should not be substituted for the all-event endpoint. General statistical interpretation of such counts relies on comparable event ascertainment and clearly defined populations; the record does not give enough detail to assess those features fully.

What is not specified?

The registry record does not report the statistical analysis plan, the model used for the primary outcome, the confidence-interval method, or the original sample-size justification. It also does not describe interim analyses, missing-data procedures, or prespecified subgroup analyses. No method should be inferred from the presence of a risk difference, confidence interval, or p-value alone. The posted calculations permit description of the results, but they do not replace the trial’s unreported analysis plan or establish which comparisons were intended to be confirmatory.

10. Confidence Intervals and Precision

The confidence intervals show substantial uncertainty for several of the posted risk-difference estimates. For JBT101 1 mg QD, the interval extends from -0.142 to 0.362; for JBT-101 5 mg QD, it extends from -0.145 to 0.371. Both include zero, so the posted intervals are compatible with no difference as well as with differences in either direction. The placebo BID comparison also has an interval including zero, from -0.078 to 0.438.

The intervals for JBT-101 20 mg QD and JBT-101 20 mg BID are above zero: 0.040 to 0.503 and 0.012 to 0.488, respectively. Their lower limits are close to zero relative to the span of the intervals, and their upper limits allow larger positive differences. These ranges indicate that the point estimates should not be treated as exact descriptions of the underlying contrast.

In general, a confidence interval is a range of values compatible with the data and the statistical method used, under its assumptions. It is not a range containing a known fixed percentage of individual outcomes, nor does it account automatically for biases or multiplicity. The confidence level and method are not reported in the registry record. The denominators in the posted groups are limited, which is relevant because estimates based on fewer participants tend to be less precise. The registry does not provide enough information to assess whether the observed participants represent the full intended analysis population.

Precision is distinct from the direction of an estimate. A positive risk difference is the observed direction of contrast in these comparisons, but the interval conveys how uncertain that estimated contrast is. The estimates should be read alongside the definitions and populations actually reported, not as definitive measures of treatment effect.

11. 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 figures are participants per arm for the listed binary-outcome comparisons, not total event counts. They illustrate how the required group size changes when the effect targeted for detection is set to 100%, 75%, or 50% of the observed effect. For example, planning for 75% of the observed effect means targeting a smaller contrast than the full observed estimate; a smaller target effect generally requires more participants to detect under the same assumptions.

The planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculation uses the observed effect as its reference, with the target effect defined as the stated fraction of that observed effect. The registry record does not report the assumptions used in the trial’s own original design or its sample-size justification. These figures are planning illustrations, not observed power.

The 80% power column gives the estimated participants per arm for a design that would have an 80% chance of detecting the specified target effect under the stated assumptions, if that effect were the true effect and the statistical model assumptions held. The 90% power column describes the corresponding planning size for a 90% chance. Neither column is a statement about the probability that the trial’s result is true. Because smaller effects are harder to distinguish from random variation, the planning sizes increase as the targeted fraction decreases.

These calculations are based on the observed estimates, which may be imprecise, especially when group denominators are limited. The resulting planning figures should not be treated as a recommendation for a future study without a separate design assessment, including the chosen endpoint, target effect, allocation, analysis plan, and allowance for missing outcomes.

12. 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 = 0.429; treatment proportion p₁ = 0.538; average p̄ = 0.484.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7067 = 1.3852.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7024 = 0.5912.
4. n = (1.3852 + 0.5912)² / (0.1099)² = 323.4, rounded up to 324 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 <- 0.428571428571429                          # control proportion
p1 <- 0.538461538461538                          # 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(2465450)
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 = 324 (80% power), 433 (90% power)
 75% of observed effect: n per arm = 575 (80% power), 769 (90% power)
 50% of observed effect: n per arm = 1,289 (80% power), 1,725 (90% power)
power.prop.test: 323.4 
Simulated power at n = 324 per arm: 0.805 (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.

13. Multiplicity, Missing Data and Analysis Populations

The posted results include several comparisons against placebo QD and a comparison of placebo BID with placebo QD. The record reports unadjusted p-values for these contrasts but does not report a multiplicity strategy. When multiple hypotheses are tested, general statistical reasoning cautions that interpreting each unadjusted p-value as if it were the sole planned test can overstate the evidence across the set of comparisons. The registry record does not say whether the comparisons were prespecified, ranked, adjusted, or intended as exploratory.

The registry does not report how missing outcome data were handled, whether any participants were excluded from an analysis, or how the analysis populations were defined beyond the statement that the adverse-event tabulation includes participants who entered Treatment Period 2 (n=81). The arm denominators vary, and the record does not explain the relationship between those denominators and the stated population. It is not reported in the registry record whether participants who did not enter Treatment Period 2 contributed to any other safety summaries.

The original statistical analysis plan, primary model, treatment of protocol deviations, and rules for censoring or follow-up are not reported in the registry record. A planned interim analysis is also not reported. It would therefore be inappropriate to infer that no interim analyses occurred, or that missingness was handled in a particular way, from the posted results alone.

These omissions limit the ability to judge whether the displayed comparisons represent the prespecified primary analysis, whether all randomized participants were included, or whether the p-values account for the full set of outcomes and dose comparisons. The posted data can still be read descriptively: they show counts, estimated contrasts, intervals, and unadjusted p-values for the listed groups. Their role in a confirmatory analysis cannot be established from the registry record.

14. 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: infective pulmonary exacerbation of cystic fibrosis (10.0%), hand fracture (3.8%), thrombosis in device (3.6%).

Serious adverse events are listed separately from the primary outcome, which counts participants with all treatment-emergent adverse events. The serious-event listing reports participants at risk and participants affected in each group. The posted affected counts are 1 for JBT101 1 mg QD, 0 for JBT-101 5 mg QD, 2 for Placebo QD, 3 for JBT-101 20 mg QD, 2 for JBT-101 20 mg BID, and 1 for Placebo BID. The registry lists deaths as 0 in every group.

The record also lists serious-event terms with percentages: Infective pulmonary exacerbation of cystic fibrosis, 10.0%; hand fracture, 3.8%; and Thrombosis in device, 3.6%. The information summarized for the trial does not clarify the denominator or calculation basis for these term percentages, so they should be read as registry-listed figures rather than recalculated participant risks.

These counts do not establish whether an event was caused by treatment, and small counts are inherently imprecise descriptions of event frequency. Serious adverse events and all treatment-emergent adverse events are different summaries and should not be conflated. The registry record does not report further details about event adjudication or causal attribution.

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

The posted primary outcome describes how many participants in each listed group experienced at least one treatment-emergent adverse event during the stated treatment period. In the comparisons with placebo QD, the estimated risk differences are positive for each listed JBT-101 regimen. The intervals for the 1 mg and 5 mg once-daily comparisons include zero, while those for the 20 mg once-daily and twice-daily comparisons are above zero. These statements describe the registered estimates and intervals; they do not establish treatment causation or a clinical conclusion.

The reported endpoint is a safety count, not a measure of symptom improvement, lung function, or another efficacy outcome. Although the study purpose includes efficacy and the record lists plasma concentrations on Day 84 as a secondary outcome, no results for those outcomes are posted in the information summarized for this trial. The primary safety results therefore cannot answer whether JBT-101 improves cystic fibrosis outcomes.

The results also do not establish the overall safety profile of JBT-101. The record concerns a phase 2 study with limited group denominators, and its serious-event counts are small. The listed events may be important for safety description, but neither the all-event endpoint nor the serious-event summary alone shows whether observed events were caused by treatment or how frequently they would occur in a broader population.

Statistical uncertainty matters: the intervals span a range of plausible contrasts, and the registry does not report how multiplicity, missing outcomes, or the original analysis plan were handled. The most defensible interpretation is therefore bounded to the posted counts and unadjusted comparisons. They describe what was recorded in the listed groups, with uncertainty, and do not by themselves justify a treatment recommendation or a claim about efficacy.

16. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is a participant-level safety count, while the registry presents several dose and schedule comparisons. That structure makes clear why effect scale, uncertainty, and multiplicity matter. A risk difference communicates an absolute contrast between group proportions, while confidence intervals indicate how much uncertainty remains around that contrast. The estimates vary across the posted regimens, and the uncertainty intervals differ in whether they include zero.

The study’s sequential model and changing regimens also make population definitions especially important. The outcome description refers to participants who entered Treatment Period 2 (n=81), while the listed group denominators vary. The registry does not explain how the groups and denominators relate to the full sequence. A statistical reader should therefore avoid assuming that all displayed contrasts have identical exposure histories or analysis populations.

The record illustrates the distinction between exploratory description and a confirmatory claim. It posts unadjusted p-values for multiple comparisons but does not report a multiplicity plan or a statistical analysis plan. Without those details, the results can be described faithfully, but the confirmatory status of individual comparisons cannot be determined from the registry record.

Finally, the planning illustrations demonstrate how sample-size requirements depend on the size of the effect a future study aims to detect. Smaller target effects require larger groups under the stated assumptions. Because these illustrations use observed effects and the registry does not report the original design rationale, they are best understood as conditional planning examples rather than evidence about the design or performance of the completed trial.

17. 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 registry record leaves several trial-specific details unresolved. It labels the model sequential and lists regimens that change across Days 1-28 and Days 29-84, but it does not explain the sequence of assignment, whether all participants followed the same transition structure, or how the posted arms map to exposure over time. Those details affect how directly the listed groups can be compared.

The primary outcome description refers to participants entering Treatment Period 2 (n=81), while the posted arm denominators differ. The registry does not reconcile this population statement with the outcome counts, nor does it report a participant flow or reasons for any differences. It is also not reported how missing data, withdrawal, or participants not entering Treatment Period 2 were handled.

The record does not report the original sample-size justification, the confidence-interval method, the primary statistical model, or the prespecified analysis plan. It does not specify whether the posted comparisons were primary, exploratory, or adjusted for multiple testing. These omissions constrain interpretation of the unadjusted p-values and the scope of inference.

Finally, the information summarized for the trial does not include posted results for the secondary plasma-concentration outcome, or detailed efficacy results. The endpoint definition does not provide further criteria for treatment-emergent events, and the serious-event listing does not explain causal attribution or the denominator behind its term percentages. Conclusions should remain limited to the registry’s reported counts and comparisons.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics, and Efficacy of JBT-101 (Lenabasum) in Cystic Fibrosis — NCT02465450.
• Registry record last updated 2018-04-04; status last verified 2018-03.
• Results first posted 2018-02-09.
• 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.

21. Record Summary

NCT02465450 is a completed, randomized, double-blind, placebo-controlled phase 2 study of JBT-101 (lenabasum) in adults with cystic fibrosis. The registry lists enrollment of 85, a sequential model, and a study purpose covering safety, tolerability, pharmacokinetics, and efficacy.

The primary outcome counts participants with treatment-emergent adverse events during 84 days of treatment. The registry describes the outcome population as participants who entered Treatment Period 2 (n=81). Posted comparisons use risk differences against placebo QD and include confidence intervals and unadjusted p-values. The record also lists serious adverse events and a secondary outcome of plasma concentrations on Day 84, but secondary analysis results are not posted in the information summarized for this trial.

Interpretation is limited by unreported details about the original analysis plan, multiplicity, missing data, and the relationship between the sequential regimen structure and the listed denominators. The posted statistics support description of the recorded safety counts and their uncertainty, not a causal or efficacy conclusion.