Long-term Study to Assess the Safety and Effectiveness of NMRA-335140 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

30 Sep 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

2023-505892-56-00

ClinicalTrials.gov

NCT06029439

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

The primary objective of the open-label, 52-week extension study is to evaluate the long-term safety and tolerability of NMRA-335140 80mg once daily (QD) in the treatment of major depressive disorder (MDD).

Secondary objectives 1

1. The secondary objective of the open-label, 52-week extension study is to evaluate the long-term effectiveness of NMRA-335140 80 mg QD.

Conditions and MedDRA coding

Major Depressive Disorder

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Completed a previous NMRA-335140 Phase 3 MDD study (NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303) according to the completion definition in the parent study protocol.
2. Signed an informed consent form (ICF) for this study. Note: For participants in the Czech Republic, every participant must have a caregiver participate in the study to help monitor compliance and safety during the study. The caregiver must be in personal contact with the participant at least 5 days a week in severely depressed participants or 2 days a week in moderately depressed participants and accompany the participant to study visits. The caregiver must sign a separate caregiver ICF.
3. Willing to comply with the contraception requirements described in the inclusion criteria of the parent study protocol.
4. Willing to comply with the concomitant medication/therapy restrictions described in the exclusion criteria of the parent study protocol.

Exclusion criteria 7

1. Diagnosed with another Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) disorder that would have been exclusionary in the parent study (eg, personality disorder, bipolar 1 or 2, schizophrenia, any other psychotic disorder, or moderate or severe substance or alcohol use disorder [excluding nicotine]).
2. Considered to be at significant risk of suicide in the judgment of the Investigator. This includes participants who are actively suicidal (eg, any suicide attempts during the parent study) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the C-SSRS ("Since Last Visit" version, score of "YES" on suicidal ideation Item 4 or 5) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator.
3. Non-adherent with study medication (took less than or equal to 70% of study drug over any 2-week visit interval) or procedures during the parent study.
4. Experienced treatment emergent adverse events (TEAEs) considered related to the study medication from the parent study and judged by the Investigator to be clinically significant to render the participant ineligible for enrollment.
5. Have an abnormality on ocular examination that would prohibit continued study participation as determined by the Investigator.
6. Use of disallowed concomitant medication or therapy that would have been exclusionary in the parent study, may compromise the safety of the participant, and/or confound the interpretation of protocol assessments.
7. Considered by the Investigator to be inappropriate for any other reason.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability assessments based on adverse events (AEs), clinical laboratory parameters, electrocardiograms (ECGs), vital signs, physical examinations, ophthalmologic examination and corneal specular microscopy (CSM), Columbia Suicide Severity Rating Scale (C-SSRS), and Change in Sexual Functioning Questionnaire-14 (CSFQ-14).

Secondary endpoints 10

1. Change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score over time.
2. Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score over time.
3. Change from baseline in the Patient Health Questionnaire-9 (PHQ-9) total score over time.
4. Change from baseline in PHQ-9 Anhedonia Item #1 over time.
5. Change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score over time.
6. Change from baseline in the Clinical Global Impression of Severity (CGI-S) score over time
7. Value at each timepoint assessed in the Clinical Global Impression of Improvement (CGI-I) score.
8. Percentage of participants whose MADRS total score decreased by greater than or equal to 50% from baseline over time.
9. Percentage of participants whose MADRS total score decreased to 10 or less over time.
10. Change from baseline in the Sheehan Disability Scale (SDS) over time.

Investigational products

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

Test 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

Paul Yeung

Third parties 11

Locations

7 EU/EEA countries · 32 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 80 files

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

Application history

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