Study of Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Participants With Treatment- Resistant Depression (TRD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Participants With Treatment- Resistant Depression (TRD) (NCT05454410), a randomized phase 2 study. The primary outcome is Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score 24 Hours (Day 2) After Injection.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group phase 2 trial sponsored by Novartis Pharmaceuticals. The registry record lists triple masking. It does not specify which roles were masked, so the practical meaning of that masking designation is not reported in the registry record. The trial enrolled 60 participants and is listed as completed.

Participants were assigned to a single subcutaneous injection of MIJ821 at 1 mg, 4 mg or 10 mg, or to a placebo injection containing 0.9% sodium chloride solution. Injections were administered on Day 1. MIJ821 and placebo were given in addition to standard of care pharmacological antidepressant treatment. The parallel-group design means participants were assigned to a treatment group rather than crossing between the study injections.

The recorded study start date is 2023-03-13, and the primary completion date is 2023-11-28. The primary outcome was change from baseline in MADRS total score 24 hours after injection. The listed primary analysis population was the Full Analysis Set: randomized participants who received a dose of randomized treatment, analyzed according to assigned group. Arm-level primary estimates are reported for 15 participants in the 10 mg group, 14 in the 4 mg group, 14 in the 1 mg group and 17 in the placebo group.

The registry record does not report the trial’s original sample-size justification, detailed eligibility criteria, or the planned statistical analysis document. The listed enrollment is a trial-level figure; it should not be confused with the analysis count for any individual outcome.

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: All inclusion and exclusion criteria were checked during screening and on Day 1, prior to randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) included all randomized participants who received a dose of the randomized treatment. Participants were analyzed according to the assigned treatment groups.

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: The Randomized set included all Randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score 24 Hours (Day 2) After Injection, measured over Baseline and 24 hours after SC injection.

The primary endpoint was change from baseline in total score on the Montgomery Åsberg Depression Rating Scale (MADRS) 24 hours after the subcutaneous injection, at Day 2. The registry describes MADRS as a clinician-rated measure designed to assess depression severity and detect changes during antidepressant treatment. It includes ratings of apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. Each of its 10 items is scored from 0, meaning the item is absent or normal, to 6, meaning symptoms are severe or continuously present. The total possible score is 0 - 60, with higher scores representing a more severe condition.

Change from baseline is used to describe how the measured score shifts over the specified period, rather than relying only on a score at a single visit. Here, the primary comparison is the difference in change between an MIJ821 group and placebo. A more negative change means a larger decrease in the MADRS score; it describes the measured scale, not by itself the clinical importance or durability of a change.

The registry reports least-squares mean changes with standard errors for the treatment groups and sponsor-reported ANCOVA mean differences. The endpoint was measured at 24 hours; later MADRS assessments are listed among secondary outcomes. The record does not establish that the 24-hour result represents a lasting change.

7. Results Posted in the Registry

• MIJ821 10 mg: mean -14.10 versus -8.90 on control; difference -5.20 (95% CI -10.43 to 0.03), standardized effect d = -0.69; z-test p = 0.051.
• MIJ821 4 mg: mean -11.40 versus -8.90 on control; difference -2.50 (95% CI -7.86 to 2.86), standardized effect d = -0.33; z-test p = 0.360.
• MIJ821 1 mg: mean -8.40 versus -8.90 on control; difference 0.50 (95% CI -4.83 to 5.83), standardized effect d = 0.07; z-test p = 0.854.

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.

Dose-response (DR) Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score at 24 Hours After Single SC Injection

• 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 errors.
• Result:
  • MIJ821 10 mg: mean -14.10 versus -8.90 on control; difference -5.20 (95% CI -10.43 to 0.03), standardized effect d = -0.69; z-test p = 0.051.
  • MIJ821 4 mg: mean -11.40 versus -8.90 on control; difference -2.50 (95% CI -7.86 to 2.86), standardized effect d = -0.33; z-test p = 0.360.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between MIJ821 10 mg 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 MIJ821 4 mg and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary questions spanning adverse events, MIJ821 pharmacokinetics, MADRS change at later visits, dose response at 24 hours, and exposure-response relationships. These outcomes address different aspects of the study: tolerability and safety, drug concentration and timing, and whether score changes vary with dose or exposure. The posted secondary results are not all reported as numerical estimates in the record, so their directions and precision cannot be reviewed uniformly.

The secondary dose-response analysis reports a multiple contrast test p-value of 0.024. This provides a result for a secondary test of the relationship between dose and change in MADRS score at 24 hours. It is related to the primary question because it concerns the same outcome and assessment time, but it is not identical to a set of pairwise MIJ821-versus-placebo comparisons. It should be considered alongside, not in place of, the primary ANCOVA results.

The registry lists 11 outcome measures and 10 posted secondary outcomes. Numerical summaries for the pharmacokinetic endpoints and for every listed secondary outcome are not available in the registry record. Consequently, the overall secondary pattern cannot be characterized from the listed endpoint titles alone. The absence of a reported estimate is not evidence that an outcome had no change or no difference.

Secondary analyses generally carry less weight than a prespecified primary analysis when many outcomes or contrasts are examined, because repeated testing increases the chance of finding an apparently notable result by chance. Adjustment strategies and testing hierarchies can address this issue, but the registry record does not report a complete multiplicity plan. The multiple contrast test is identified by name, but its role in the full analysis hierarchy is not described. Results across endpoints should therefore be interpreted cautiously, with attention to their exploratory or confirmatory status as reported in the protocol; that status is not fully reported in the registry record.

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

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Including Adverse Events of Special Interest (AESIs)
• Pharmacokinetics (PK) of MIJ821 in Plasma for Area Under the Curve From the Time of Dosing to the Time of the Last Measurable Concentration (AUClast)
• PK of MIJ821 in Plasma for Maximum Serum Concentration (Cmax)
• PK of MIJ821 in Plasma for Time to Maximum Drug Concentration (Tmax)
• Change From Baseline in the MADRS Total Scores at Day 8, 15, 22 and 29 Visits
• Dose-response (DR) Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score at 24 Hours After Single SC Injection
• Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameters: Placebo Effect E0, Emax
• Exposure-response Relationship of MIJ821 With Respect to Change From Baseline in MADRS Total Score. Estimated Parameter: EC50 (Cmax)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score, and the reported group summaries are least-squares mean changes. An estimated mean summarizes the average change in a group, while a standard error describes the uncertainty of that estimated mean. The standard error is not the same as the spread of individual participants’ scores. The registry record does not report individual-level data, so the range of personal responses cannot be inferred from these group summaries.

What does an ANCOVA comparison do?

ANCOVA is a regression-based method that compares groups while accounting for a measured covariate. The sponsor reports ANCOVA mean differences (net) for each MIJ821 dose versus placebo. The particular covariates and model specification are not reported in the registry record. Therefore, the posted adjusted estimates cannot be independently reconstructed from the arm means alone. An adjusted estimate may differ slightly from a comparison made directly from summary means because it can reflect the model and covariate adjustment.

The sponsor’s mean difference is expressed as an MIJ821-group change relative to placebo. A negative value indicates a greater reduction in MADRS score in the MIJ821 group than in placebo, given the score’s direction. The confidence interval expresses the range of effects compatible with the model and its assumptions at the stated confidence level. An interval including zero is compatible with no difference as well as with effects in either direction; an interval entirely on one side of zero does not, on its own, convey clinical importance.

What is the role of the recalculation?

The recalculated comparisons use the posted arm means and standard errors to construct approximate unadjusted comparisons. The pooled standard deviation is also approximate, as indicated in the record. These calculations are useful as a transparent check on the direction and rough scale of the contrasts, but they do not reproduce ANCOVA. They do not use individual participant data or the sponsor’s covariate model. The recalculated p-values are unadjusted and should not be interpreted as if they account for testing several dose comparisons or endpoints.

A p-value describes how unusual the data, or more extreme data, would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. A p-value just above a conventional threshold is not proof of no effect; likewise, a smaller p-value does not establish that an effect is clinically meaningful. The registry does not give sponsor p-values for the primary ANCOVA comparisons, so the sponsor estimates and confidence intervals are the central reported inferential results.

Why does the secondary dose-response test differ?

The record reports a multiple contrast test for the secondary dose-response relationship, with p = 0.024. A multiple contrast test evaluates a set of contrasts designed to examine a pattern across treatment groups, rather than treating each dose-versus-placebo comparison as an isolated test. The registry record does not report the contrasts used, the detailed model, or how this test fits into any broader testing hierarchy. Its result should therefore be read as evidence from that specified secondary analysis, not as a replacement for the primary ANCOVA results.

The dose groups’ estimated mean changes are not themselves a formal dose-response test. A pattern in group means can be informative descriptively, but a formal test depends on its model and assumptions. The secondary test’s reported p-value supplies an inferential result for the dose-response question, while the missing detail limits independent assessment of its construction.

What do the standard errors and confidence intervals tell readers?

The standard errors accompanying the arm estimates reflect the precision of the estimated group means. Confidence intervals for comparisons incorporate uncertainty in the contrast. Wider intervals indicate less precision, while narrower intervals indicate greater precision, under the analysis assumptions. Uncertainty depends on factors including variation in the outcome, the number of observed participants, and the analysis method. General statistical principles explain these relationships, but the registry record does not provide participant-level distributions or the full model output needed to examine them further.

The sponsor reports 90% confidence intervals for the ANCOVA contrasts. The recalculated comparisons include their own intervals and unadjusted p-values; they are a different calculation and should not be blended with the sponsor’s intervals. The confidence level and model matter when interpreting an interval. Neither an interval nor a p-value answers whether the result is important to participants, whether it persists, or how it compares with other treatments.

The primary population is described as the Full Analysis Set, including randomized participants who received a dose and analyzed according to assigned group. This definition helps clarify whose outcomes contribute to the reported primary estimates. The registry does not report detailed handling of missing endpoint values, protocol deviations, or sensitivity analyses. Those omissions matter because the result can depend on which observations are available and how missing values are treated.

11. Confidence Intervals and Precision

The sponsor ANCOVA estimate for MIJ821 10 mg versus placebo is -5.2, with a 90% confidence interval from -9.6 to -0.7. The interval lies below zero, indicating that the sponsor’s model-based estimate is compatible with a greater reduction in MADRS score for the 10 mg group over this assessment period. The interval also communicates uncertainty: the estimated contrast is not a single known value. The registry record does not report the corresponding p-value.

For 4 mg, the estimate is -2.5 and the 90% confidence interval runs from -7.0 to 2.1. For 1 mg, the estimate is 0.6 and the interval runs from -4.0 to 5.1. Both intervals include zero and span possible contrasts in either direction. They therefore do not pin down the direction of the between-group difference with the same clarity as an interval wholly on one side of zero. Their widths also indicate that a range of values remains compatible with each estimate.

The recalculated intervals are not the same as the sponsor’s ANCOVA intervals. For example, the recalculated 10 mg comparison has an interval from -10.43 to 0.028, while the sponsor’s 90% interval is from -9.6 to -0.7. The recalculation uses approximate, unadjusted summary-statistic methods; the sponsor analysis uses ANCOVA. The two should be interpreted as different analyses rather than combined into one interval. The recalculated 10 mg interval includes zero, whereas the sponsor’s reported interval does not.

A confidence interval indicates statistical uncertainty under the method used; it is not a guarantee that the true effect falls inside the interval. Precision is also distinct from clinical importance. The registry record does not report a threshold for a clinically important MADRS change, so the clinical meaning of the estimated differences cannot be determined from these intervals 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 planning figures are participants per arm, not total events. They are planning illustrations computed from the observed effect, using 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. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the assumptions are correct. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not probabilities that the observed result is correct. They are not observed power.

Rows using 100% of the observed effect use the observed contrast as the planning target; rows using 75% or 50% use smaller target effects. Smaller effects are harder to distinguish from random variation, so the planning calculations require more participants per arm as the target effect gets smaller. The figures are specific to each comparison’s observed effect and variability, so they should not be treated as a universal sample-size recommendation.

The illustrations are retrospective planning scenarios based on observed estimates, not evidence that the trial was originally designed around those assumptions. They also do not incorporate any unreported features of the original protocol or analysis plan. For continuous outcomes, the stated unit is participants per arm; the registry’s general convention for time-to-event outcomes is total number of events, but the primary outcome is continuous.

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 = -5.200; pooled standard deviation σ = 7.527.
2. n = 2 × (1.96 + 0.842)² × 7.527² / -5.200² = 32.9, rounded up to 33 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 <- -5.2                      # observed difference in means
sigma <- 7.52661455547357                     # 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(5454410)
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 = 33 (80% power), 45 (90% power)
 75% of observed effect: n per arm = 59 (80% power), 79 (90% power)
 50% of observed effect: n per arm = 132 (80% power), 177 (90% power)
power.t.test: 33.9 
Simulated power at n = 33 per arm: 0.787 (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

The sponsor’s primary results are ANCOVA mean differences (net) with 90% confidence intervals. These are the main reported between-group analyses for the primary endpoint. For the 10 mg comparison, the sponsor estimate is -5.2, with a 90% interval from -9.6 to -0.7. The sponsor estimates for 4 mg and 1 mg are -2.5 and 0.6, with intervals from -7.0 to 2.1 and from -4.0 to 5.1, respectively. The registry record does not report p-values for these primary ANCOVA comparisons.

The recalculations use posted group summaries to make simple, unadjusted comparisons. They give estimates of -5.2, -2.5 and 0.5 for 10 mg, 4 mg and 1 mg, respectively, with unadjusted p-values of 0.051, 0.36 and 0.854. They are not adjusted for the ANCOVA model and are not a reproduction of the sponsor analysis. In particular, a recalculated confidence interval or p-value should not be substituted for the sponsor’s reported result.

The registry record does not flag a discrepancy. The sponsor analysis and the recalculation are best read as results from methods with different adjustment and assumptions. The sponsor’s ANCOVA analysis is the registry’s reported analysis for the primary comparisons; the recalculation offers a separate summary-statistic view, not a competing definitive analysis.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis evaluates several treatment comparisons, outcomes, time points, or other hypotheses. Without an appropriate plan, the chance of at least one apparently positive result can increase as more tests are considered. This is a general statistical concern, not a claim that any particular result in this trial is invalid.

The primary endpoint has three MIJ821 dose groups compared with placebo. The registry record reports sponsor ANCOVA estimates and 90% confidence intervals for these comparisons, but does not report primary p-values or a detailed strategy for controlling multiplicity across the dose comparisons. The secondary outcomes include repeated MADRS assessments, safety outcomes, pharmacokinetic outcomes, and exposure-response questions. A complete prespecified testing hierarchy or adjustment plan is not reported in the registry record.

The dose-response secondary analysis uses a multiple contrast test and reports p = 0.024. That method can address a specified family of contrasts, but the registry record does not describe the contrast set or how its result relates to the broader family of primary and secondary tests. It is not possible to determine from the record whether all relevant testing was controlled under a single study-wide strategy.

The primary population is defined as the Full Analysis Set: randomized participants who received a dose, analyzed according to assigned treatment. The record does not detail missing-data handling for the primary endpoint, the amount of missing endpoint information, or sensitivity analyses assessing assumptions about missing outcomes. It also does not report whether any participants were excluded from the primary analysis after dosing or why. Those details are important for judging how robust the estimates are to incomplete observations.

These are limits on what can be concluded from the registry record, rather than evidence that a particular analysis was mishandled. The detailed protocol and statistical analysis plan are not reported in the registry record, so the intended treatment of multiplicity, missing data and analysis populations beyond the stated FAS definition cannot be confirmed.

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 non-serious adverse event terms

The serious adverse event figures report 0 affected participants in each listed group: MIJ821 10 mg, MIJ821 4 mg, MIJ821 1 mg, placebo, all MIJ821 groups combined, and all participants. The record also reports 0 deaths in each of those group summaries. These are counts of participants with reported serious adverse events, not a statement that no adverse events of any kind occurred.

Other adverse events were reported separately: 10 participants in the 10 mg group, 6 in the 4 mg group, 4 in the 1 mg group and 7 in the placebo group were recorded as affected. These are not serious-event counts and should not be conflated with the serious adverse event figures. The registry lists adverse events of special interest among the secondary safety outcomes but does not provide event-level detail in the registry record for this summary.

Zero serious adverse events in these groups is a descriptive finding for this trial. It does not establish that serious events cannot occur, particularly because the study enrolled 60 participants and the record does not provide detailed information about event surveillance, duration of follow-up for safety, or the precision of event-rate estimates. The figures should be read as observed counts in this study, not as a general guarantee about safety.

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

The primary endpoint asks whether MADRS scores changed differently over the short interval after injection in the MIJ821 groups compared with placebo. The sponsor ANCOVA estimate for 10 mg is in the direction of a larger decrease than placebo, with a 90% confidence interval below zero. The sponsor estimates for the 4 mg and 1 mg comparisons have intervals that include zero. These findings describe the registry’s reported analyses; they do not by themselves establish a clinical benefit, a dose recommendation, or a lasting effect.

A score change is a measurement on a clinician-rated scale. Interpretation requires more than the sign of a mean difference: the size of the difference, its uncertainty, the clinical meaning of that size, and the quality of the analysis all matter. The registry record does not report a threshold for a clinically important change in MADRS, so the estimated contrast cannot be classified against such a threshold from the record alone.

The endpoint is assessed 24 hours after a single injection. Secondary MADRS outcomes include later visits, but their numerical results are not reported in the information available for this summary. The primary result therefore does not establish whether a difference persists at later assessments. It also does not answer whether results would apply to people outside the trial population or to a different treatment regimen.

The study includes a placebo group receiving standard of care and several MIJ821 dose groups, which supports comparisons within the randomized trial. Nonetheless, the enrollment and reported analysis groups are limited in size, and the registry does not report the full protocol, missing-data sensitivity analyses or detailed multiplicity plan. The result should be understood as evidence from this specific phase 2 trial and analysis, not as a definitive conclusion about all people with treatment-resistant depression.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment-group mean change and a between-group contrast answer different questions. Each group’s MADRS score decreased on average, including placebo. The comparative estimate accounts for the placebo-group change and is more directly relevant to the study’s question than either group’s change considered alone. This distinction is important whenever outcomes can shift over time for reasons other than the study treatment.

The record also demonstrates that the apparent conclusion can depend on the analysis method. The sponsor’s ANCOVA results and the simple unadjusted recalculations are related but not interchangeable. ANCOVA uses a model-based adjustment whose full specification is not reported in the registry record; the recalculations rely on posted group summaries and approximate variability. Reading both without treating them as equivalent helps distinguish an independent check from the sponsor’s main analysis.

Precision matters alongside the point estimate. The 10 mg sponsor interval is on one side of zero, while the lower-dose intervals include zero and allow a range of possible contrasts. The secondary dose-response test adds another type of evidence, but its interpretation depends on its place among multiple comparisons and outcomes. The record does not fully describe the testing hierarchy, which limits assessment of how much weight to give that secondary finding.

Finally, the trial includes safety, pharmacokinetic and repeated symptom outcomes, but the registry record does not report numerical results for every listed endpoint. Distinguishing observed counts, estimated mean changes, uncertainty intervals and unreported outcomes is part of sound statistical reading. The available results inform the questions this study measured; they do not settle clinical importance, durability or generalizability.

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 assessment is at 24 hours after a single injection. That short-term endpoint cannot establish persistence, and later MADRS outcomes are listed without numerical results in the registry record. No inference about the longer-term course can be made from the primary endpoint alone.

The sponsor ANCOVA model is not fully described. Covariates, model diagnostics and handling of missing observations are not reported in the registry record. The primary population definition is available, but the record does not give detailed participant flow into the endpoint analysis or sensitivity analyses for missing data. The recalculations are approximate and unadjusted, so they cannot fill those gaps.

The record does not give a full multiplicity plan covering the dose comparisons and secondary outcomes. The secondary multiple contrast test is identified, but its contrast construction and relationship to any prespecified testing hierarchy are not reported. The p-value from this secondary test should not be read as resolving the uncertainty around the primary pairwise comparisons.

Numerical results for many listed secondary outcomes, including pharmacokinetic measures, are not reported in the record used for this summary. The serious adverse event counts are descriptive, and the record does not provide detailed event terms or a complete account of exposure and follow-up time for safety interpretation. The listed total enrollment and group outcome counts do not provide the details needed to assess all exclusions or incomplete measurements.

Lastly, the registry record does not report the original sample-size justification, the detailed protocol, or the complete statistical analysis plan. The planning illustrations based on observed effects should not be mistaken for the trial’s original design rationale. These limitations do not negate the reported results, but they constrain independent evaluation and the scope of conclusions.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study of Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Participants With Treatment- Resistant Depression (TRD) — NCT05454410.
• Registry record last updated 2025-04-13; status last verified 2025-04.
• Results first posted 2025-04-04.
• 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

NCT05454410 is a completed randomized, double-blind, placebo-controlled, parallel-group phase 2 trial of a single subcutaneous MIJ821 injection added to standard of care in participants with treatment-resistant depression. The study compared MIJ821 doses of 1 mg, 4 mg and 10 mg with placebo.

The primary outcome was change from baseline in MADRS total score 24 hours after injection. The sponsor reported ANCOVA comparisons with 90% confidence intervals; the 10 mg estimate was -5.2, while the 4 mg and 1 mg estimates were -2.5 and 0.6. The registry also reports a secondary dose-response multiple contrast test p-value of 0.024. Serious adverse events and deaths were reported as 0 across the listed groups, while other adverse events were reported separately.

The registry record does not report the full analysis plan, the original sample-size justification, detailed missing-data methods, or numerical results for every secondary outcome. The findings therefore describe the posted analyses and observed outcomes, with limits on conclusions about durability, clinical importance and broader applicability.