Trial · NCT04221230
Study in Major Depressive Disorder With NMRA-335140 (BTRX-335140) vs Placebo
NCT04221230, Phase 2, Completed, Neumora Therapeutics, Inc.; results first posted 2025-05-29
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study in Major Depressive Disorder With NMRA-335140 (BTRX-335140) vs Placebo. Trials, record NCT04221230. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04221230
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study in Major Depressive Disorder With NMRA-335140 (BTRX-335140) vs Placebo
- NCT number
- NCT04221230
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 204 participants, actual
- Lead sponsor
- Neumora Therapeutics, Inc.
- Conditions
- Major Depressive Disorder
- Interventions
- NMRA-335140, Placebo
- First posted
- 2020-01-09
- Last updated
- 2025-05-29
- Results first posted
- 2025-05-29
Source ClinicalTrials.gov
Registered outcomes18
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Change From Baseline in Hamilton Depression Rating Scale (HAMD-17) Total Score at Weeks 8 | Baseline and at Week 8 | The HAMD-17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (9 items) or 0 and 2 (8 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represents more severe condition. Baseline is defined as the latest non-missing measurement prior to or within 1 hour of the first administration of study drug. Change from Baseline is defined as post dose visit value minus Baseline value. |
| Secondary | Clinical Global Impression of Improvement (CGI-I) Score | At Week 8 | The CGI-I scale is a clinician-rated instrument that measures the improvement of the participant's symptoms. It is a 7-point scale where a score of 1 indicates that the participants is "very much improved," a score of 4 indicates that the participant has experienced "no change, and a score of 7 indicates that the participant is "very much worse." The total score is the item response; lower scores indicate greater improvement. |
| Secondary | Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score | Baseline and at Week 8 | The SHAPS is a self-report 14-item, instrument, developed for the assessment of hedonic capacity. Participants score whether they experience pleasure in performing a list of activities or experiences. Participants can rate the answers as "definitely/strongly agree", "agree", "disagree" or "strongly disagree". "Definitely agree" will be rated 1, "Agree" will be rated 2, "Disagree" will be rated 3, and "Definitely disagree" will be rated 4. The participant's item responses are summed to provide a total score ranging from 14 to 56. A higher total SHAPS score indicates higher levels of current anhedonia. Baseline is defined as the latest non-missing measurement prior to or within 1 hour of the first administration of study drug. Change from Baseline is defined as post dose visit value minus Baseline value. |
| Secondary | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscales (ie, Anxiety Subscale [HADS-A] and Depression Subscale [HADS-D]) Scores | Baseline and at Week 8 | The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-report questionnaire with 2 subscales: anxiety and depression. Seven of the items are used to evaluate anxiety and 7 evaluate depression. Each item on the questionnaire is scored from 0 to 3. Therefore, the anxiety subscale (HADS-A) and the depression subscale (HADS-D) each range from 0 to 21. Higher scores indicate higher levels of anxiety and depression, respectively. Baseline is defined as the latest non-missing measurement prior to or within 1 hour of the first administration of study drug. Change from Baseline is defined as post dose visit value minus Baseline value. |
| Secondary | Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score | Baseline and at Week 8 | The HAM-A was administered to assess severity of anxiety, its improvement during the course of treatment, and the timing of such improvement. This instrument was completed by qualified and trained investigator site raters based on a semi-structured interview of his/her assessment of the participant. The HAM-A is a 14-item scale to measure severity of different anxiety-related symptoms in participants. Each of the 14 items is rated by the clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree) with a total score range of 0 to 56 where higher score indicates greater symptom severity. Baseline is defined as the latest non-missing measurement prior to or within 1 hour of the first administration of study drug. Change from Baseline is defined as post dose visit value minus Baseline value. |
| Secondary | Change From Baseline in Sheehan Disability Scale (SDS) Scores | Baseline and at Week 8 | The Sheehan Disability Scale (SDS) is a 3-item self-rated questionnaire used to evaluate impairments in the domains of work/school, social life, and family life/home responsibility on a 10-point visual analog scale. In each domain of the overall scale, the minimum score is a 0 (indicating that symptoms have been 'not at all' disruptive to functioning) and the maximum score is a 10 (indicating that symptoms have been 'extremely' disruptive to functioning). The three items were summed into a single dimensional measure of global functional impairment with total score ranging from 0 (unimpaired) to 30 (highly impaired) with the highest scores representing the higher level of disability/greater functional impairment. SDS Total Score is calculated for subjects with all 3 domain scores (work/school, social, and family life) and an unmarked checkbox for "No work or school". Baseline is defined as Day 1. Change from Baseline is defined as the post dose visit value minus the Baseline value. |
| Secondary | Change From Baseline to Week 8 in Clinical Global Impression Scale - Severity (CGI-S) Scores | Baseline and at Week 8 | The CGI-S is a clinician-rated instrument that measures the severity of depression at the time of assessment. This rating is based upon observed and reported symptoms, behavior, and function in the past 7 days. The score reflected the average severity level across the 7 days. The CGI-S is scored on a 7-point scale where a score of 1 indicates that the participant is normal, not at all ill, a score of 4 indicates that the participant is moderately ill, and a score of 7 indicates that the participant is among the most extremely ill participants. Baseline is defined as the latest non-missing measurement prior to or within 1 hour of the first administration of study drug. |
| Secondary | Percentage of Participants With a HAMD-17 Response | At Week 8 | The HAMD-17 is a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (9 items) or 0 and 2 (8 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. HAMD-17 response rate, where response is defined as ≥ 50% decrease in HAMD-17 total score from Baseline to Week 8. |
| Secondary | Number of Participants Reporting >2% Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) | Up to 8 Weeks | An AE is any event that was not present prior to the initiation of study treatment, or any event already present that worsens in either intensity or frequency following exposure to study treatment. A TEAE is any event that was not present prior to the initiation of study treatment, or any event already present that worsens in either intensity or frequency following exposure to study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the above outcomes. |
| Secondary | Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to 8 Weeks | Blood samples were collected for the analysis of hematology parameters - basophils, eosinophils, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and reticulocytes |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 registered outcomesOutcomes18
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Change From Baseline in Hamilton Depression Rating Scale (HAMD-17) Total Score at Weeks 8 | Baseline and at Week 8 | Final Efficacy population comprised of the Full Efficacy population but excluded 5 subjects from a single site due to GCP noncompliance that compromised data integrity. Only those participants with data available at specified time points has been presented. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Clinical Global Impression of Improvement (CGI-I) Score | At Week 8 | Final Efficacy Population. Only those participants with data available at specified timepoints has been presented. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score | Baseline and at Week 8 | Final Efficacy Population. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscales (ie, Anxiety Subscale [HADS-A] and Depression Subscale [HADS-D]) Scores | Baseline and at Week 8 | Final Efficacy Population. Only those participants with data available at specified timepoints has been presented. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score | Baseline and at Week 8 | Final Efficacy Population. Only those participants with data available at specified timepoints has been presented. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline in Sheehan Disability Scale (SDS) Scores | Baseline and at Week 8 | Final Efficacy Population. Only those participants with data available at specified timepoints has been presented. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 8 in Clinical Global Impression Scale - Severity (CGI-S) Scores | Baseline and at Week 8 | Final Efficacy Population. Only those participants with data available at specified timepoints has been presented. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Percentage of Participants With a HAMD-17 Response | At Week 8 | Final Efficacy Population. Only those participants with data available at specified timepoints has been presented | Percentage of participants | NUMBER |
| SECONDARY | Number of Participants Reporting >2% Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) | Up to 8 Weeks | Safety Population. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to 8 Weeks | Safety Population. | Participants | COUNT_OF_PARTICIPANTS |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 outcomesResults by group42
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Change From Baseline in Hamilton Depression Rating Scale (HAMD-17) Total Score at Weeks 8 | NMRA-335140 | -9.0 | Standard Error 0.73 | Scores on a scale | |
| Change From Baseline in Hamilton Depression Rating Scale (HAMD-17) Total Score at Weeks 8 | Placebo | -7.4 | Standard Error 0.79 | Scores on a scale | |
| Clinical Global Impression of Improvement (CGI-I) Score | NMRA-335140 | 2.4 | Standard Error 0.13 | Scores on a scale | |
| Clinical Global Impression of Improvement (CGI-I) Score | Placebo | 2.7 | Standard Error 0.14 | Scores on a scale | |
| Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score | NMRA-335140 | -7.7 | Standard Error 0.81 | Scores on a scale | |
| Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score | Placebo | -4.8 | Standard Error 0.88 | Scores on a scale | |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscales (ie, Anxiety Subscale [HADS-A] and Depression Subscale [HADS-D]) Scores | NMRA-335140 | HADS-A Score | -3.6 | Standard Error 0.39 | Scores on a scale |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscales (ie, Anxiety Subscale [HADS-A] and Depression Subscale [HADS-D]) Scores | Placebo | HADS-A Score | -3.3 | Standard Error 0.43 | Scores on a scale |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscales (ie, Anxiety Subscale [HADS-A] and Depression Subscale [HADS-D]) Scores | NMRA-335140 | HADS-D Score | -4.8 | Standard Error 0.55 | Scores on a scale |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscales (ie, Anxiety Subscale [HADS-A] and Depression Subscale [HADS-D]) Scores | Placebo | HADS-D Score | -4.3 | Standard Error 0.60 | Scores on a scale |
1 to 10 of 42Source ClinicalTrials.gov
See all 42 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | NMRA-335140 | 102 | |
| Overall Study | STARTED | Placebo | 102 | |
| Overall Study | COMPLETED | NMRA-335140 | 72 | |
| Overall Study | COMPLETED | Placebo | 64 | |
| Overall Study | NOT COMPLETED | NMRA-335140 | 30 | |
| Overall Study | NOT COMPLETED | Placebo | 38 |
Source ClinicalTrials.gov
Adverse events12
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | COVID-19 | Infections and infestations | NMRA-335140 | 4 | 102 | |
| other | COVID-19 | Infections and infestations | Placebo | 3 | 102 | |
| other | Upper respiratory tract infection | Infections and infestations | NMRA-335140 | 3 | 102 | |
| other | Upper respiratory tract infection | Infections and infestations | Placebo | 1 | 102 | |
| other | Nausea | Gastrointestinal disorders | NMRA-335140 | 5 | 102 | |
| other | Nausea | Gastrointestinal disorders | Placebo | 1 | 102 | |
| other | Diarrhoea | Gastrointestinal disorders | NMRA-335140 | 2 | 102 | |
| other | Diarrhoea | Gastrointestinal disorders | Placebo | 3 | 102 | |
| other | Headache | Nervous system disorders | NMRA-335140 | 5 | 102 | |
| other | Headache | Nervous system disorders | Placebo | 5 | 102 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | NMRA-335140 | 0 | 102 |
| Total, all-cause mortality | Placebo | 0 | 102 |
| Total, other adverse events | NMRA-335140 | 19 | 102 |
| Total, other adverse events | Placebo | 13 | 102 |
| Total, serious adverse events | NMRA-335140 | 0 | 102 |
| Total, serious adverse events | Placebo | 1 | 102 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 40199329 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons11
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Ophthalmologic Examination Findings | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Urinary Parameters | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Vital Parameters | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants Reporting Clinically Significant Response to Clinical Opiate Withdrawal Scale (COWS) | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Hematology Parameters | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants Reporting Suicidal Behaviors or Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Trial comparisons |
| NMRA-335140 vs Placebo: Number of Participants With Clinically Significant Changes in Physical Examinations | Trial comparisons |
| NMRA-335140 vs Placebo: deaths from any cause | Trial comparisons |
1 to 10 of 11
See all 11 trial comparisonsTests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT04221230
GET https://conductscience.org/api/trials/v1/NCT04221230/results?page=2