Neumora's Navacaprant Trial Completes as Prior Phase 3 Cousin Already Failed
NCT06058039 finished with 422 patients and no posted results, arriving after Neumora's KOASTAL-1 missed its MADRS endpoint against placebo in December 2024.
Executive Summary
- NCT06058039, one of three registrational Phase 3 trials of navacaprant in major depressive disorder, was marked Completed on 2026-07-06 with enrollment revised to 422 from an earlier anticipated 332, but no endpoint result has been posted to ClinicalTrials.gov.
- The only other completed Phase 3 navacaprant trial, KOASTAL-1, failed its identical MADRS-based primary endpoint against placebo in December 2024, meaning this trial's undisclosed result now carries the weight of confirming or reversing that miss.
- Neumora guided investors to a joint KOASTAL-2/KOASTAL-3 topline readout in Q2 2026, a window that closed June 30; the registry status change lands after that window with data still unreported.
- AppliedXL's readout-timing model expects topline data around August 12, 2026, with a 39% chance of a readout within 90 days and 72% within 180 days, an estimate resting on operational and peer-cohort patterns, not on any disclosed clinical signal from this trial.
- The reader should treat this status change as an operational marker, not a result: the real catalyst is the still-pending topline readout, and its outcome will determine whether navacaprant's Phase 2 promise survives a second and third Phase 3 test.
The registry update
ClinicalTrials.gov shows NCT06058039, titled "Study to Assess the Effects of Oral NMRA-335140 in Participants With Major Depressive Disorder," moved from Active, not recruiting to Completed on July 6, 2026, the same day its enrollment count was revised from an anticipated 332 to an actual 422 NCT06058039Study to Assess the Effects of Oral NMRA-335140 in Participants With Major Depressive DisorderNCT06058039. The trial tests oral navacaprant against placebo on the primary endpoint of change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated measure of depressive symptom severity scored from 0 to 60. No results have been posted to ClinicalTrials.gov. The registry update alone does not tell readers whether the drug worked.
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The prior failure
Neumora's only other completed Phase 3 trial of navacaprant, KOASTAL-1 (NCT06029426), used the identical MADRS-based primary endpoint and failed: the company announced on January 2, 2025, that navacaprant "showed no difference from a placebo". Neumora's aggregate Phase 3 track record for navacaprant in MDD stands at zero successes against one disclosed failure across trials with outcome data on file. That history is why this trial's undisclosed result carries more weight than a routine completion: a second miss on the same endpoint would extend the pattern across two of three registrational trials.
The earlier positive signal
The program's rationale rests on a Phase 2 trial (NCT04221230) that reported statistically significant reductions in depression symptoms measured by HAMD-17 and in anhedonia measured by SHAPS, published in May 2025. That result is the clinical basis for continuing into Phase 3. Whether it generalizes to a larger, more heterogeneous Phase 3 population is exactly what KOASTAL-1 failed to confirm and what this trial's unreported data will test again.
Guidance versus reality
Neumora told investors it expected a joint topline data readout for KOASTAL-2 and KOASTAL-3, believed to include this trial, in the second quarter of 2026. That window closed June 30, and the registry shows only a status change to Completed on July 6, with no accompanying result NCT06058039Study to Assess the Effects of Oral NMRA-335140 in Participants With Major Depressive DisorderNCT06058039. AppliedXL's protocol-stability review separately flags the trial's history: three primary completion date changes, a cumulative delay the model estimates at 429 days, and a 27.1% enrollment increase, all logged in the same July 6 update.
Model basis
AppliedXL's readout-timing model puts a point estimate of August 12, 2026, on when topline data are likely to post, with a 39% probability within 90 days and 72% within 180 days. That estimate rests mostly on an ML-dominant ensemble trained on peer-cohort timing patterns (85% ML weight, 15% formulaic), not on any signal drawn from this trial's own clinical data. The clinical-significance score of 49.6% carried in the model is driven overwhelmingly by structural features, trial country count, enrollment per arm, and therapeutic-area base rates, rather than by endpoint quality or target biology, both of which pull in the opposite direction. That mix means the number reflects operational plausibility more than a read on whether navacaprant itself works.
The competitive frame
AbbVie's icalcaprant, a Phase 2 kappa opioid receptor antagonist in MDD, is the closest direct comparator on target and mechanism. Across the OPRK1-in-MDD field, 14 trials from four sponsors have produced a 50% Phase 3 failure rate, three completed and three terminated. That failure rate sets the backdrop against which this trial's still-unknown result will be read.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.