A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Oral NMRA-335140 versus Placebo in Participants with Major Depressive Disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neumora Therapeutics Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

18 Jul 2024 → ongoing

Decision date (initial)

2024-07-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Neumora Therapeutics, Inc.

External identifiers

EU CT number

2023-506335-15-00

ClinicalTrials.gov

NCT06058039

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the efficacy of 80 mg/day of NMRA335140, a kappa opioid receptor antagonist, relative to placebo on symptoms of depression in adult participants with major depressive disorder (MDD) following 6 weeks of doubleblind treatment

Secondary objectives 9

1. Participant reported symptoms of anhedonia. Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score. Change from Baseline to each timepoint assessed in the SHAPS total score
2. MADRS response rate. Percentage of participants whose MADRS total score decreased by greater than or equal to 50% from Baseline.
3. MADRS scores over time. Change from Baseline to each timepoint assessed in MADRS total scores.
4. Clinical assessment of MDD severity and improvement. Change from Baseline to each timepoint assessed in Clinical Global Impression of Severity (CGIS) score. Value at each timepoint assessed in Clinical Global Impression of Improvement (CGI-I) score
5. Participant reported symptoms of MDD. Change from Baseline to each timepoint assessed in Patient Health Questionnaire9 (PHQ9) total score
6. Participant reported severity of anhedonia. Change from Baseline to each timepoint assessed in PHQ9 Anhedonia Item #1
7. Clinician reported symptoms of anxiety. Change from Baseline to each timepoint assessed in the Hamilton Anxiety Rating Scale (HAMA) total score
8. Participant reported assessment of functional impairment. Change from Baseline at Week 6 assessed in the Sheehan Disability Scale (SDS) total score
9. MADRS remission rate. Percentage of participants whose MADRS total score decreased to 10 or less

Conditions and MedDRA coding

Major Depressive Disorder

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Have a primary Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) diagnosis of MDD without psychotic features confirmed by Structured Clinical Interview for DSM 5 Disorders, Clinical Trials Version (SCID 5 CT) at screening (this may be a first or recurrent episode).
2. Participant's current major depressive episode must be confirmed by independent assessment.
3. The symptoms of the current MDD episode have been present for more than 4 weeks prior to the Screening Visit, but no longer than 12 months prior to the Screening Visit.
4. Have a MADRS total score of 25 or higher at Screening and Baseline.
5. A change in MADRS total score between Screening and Baseline of ≤20%.

Exclusion criteria 5

1. Have failed 2 or more courses of antidepressant treatment at sufficient doses for at least 6 to 8 weeks for the current MDD episode.
2. Currently or in the past year have been diagnosed with a personality disorder per the DSM-5-TR or in the past 3 years have been diagnosed with any of the following DSM-5-TR disorders: anorexia nervosa, bulimia nervosa, or binge eating disorder. Participants with comorbid generalized anxiety disorder, social anxiety disorder, simple phobias, or panic disorder for whom MDD is considered the primary diagnosis are not excluded.
3. Have a lifetime diagnosis of bipolar 1 or 2, schizophrenia or schizoaffective, schizophreniform, obsessive compulsive disorder, or post-traumatic stress disorder (PTSD).
4. Have moderate to severe substance or alcohol use disorder, per DSM-5-TR criteria, within the 12 months prior to screening (excluding nicotine).
5. Are actively suicidal (eg, any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) (score of "YES" on suicidal ideations Item 4 or 5 within 3 months prior to Visit 1 [Screening]) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator. Participants who are currently hospitalized for MDD symptoms or suicidality are not allowed into the study. If there is a recent history (within 3 months of screening) of hospitalization due to MDD symptoms, the participant should be discussed with the Medical Monitor for eligibility.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the treatment difference in change from Baseline to Week 6 in the MADRS total score.

Secondary endpoints 1

1. The secondary endpoint is the change from Baseline to Week 6 assessed in the SHAPS total score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neumora Therapeutics Inc.

Sponsor organisation

Neumora Therapeutics Inc.

Address

260 Arsenal Place Suite 1

City

Watertown

Postcode

02472-3171

Country

United States

Scientific contact point

Organisation

Neumora Therapeutics Inc.

Contact name

Paul Yeung

Public contact point

Organisation

Neumora Therapeutics Inc.

Contact name

[email protected]

Third parties 17

Locations

7 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 103 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications