Study in Major Depressive Disorder With NMRA-335140 (BTRX-335140) vs Placebo

NCT04221230 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: K2-MDD-201NMRA-140
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 38

Brief Summary

A proof of concept (POC) study evaluating the impact of NMRA-335140 (BTRX-335140) relative to placebo on symptoms of major depressive disorder (MDD) in adult participants with MDD and symptoms of anhedonia and anxiety following 8 weeks of double-blind treatment as assessed by the HAMD-17 Scale.

Conditions

Major Depressive Disorder

Keywords

NMRA-335140; Neumora; NMRA-140; Navacaprant

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hamilton Depression Rating Scale (HAMD-17) Total Score at Weeks 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.

  Baseline and at Week 8

Secondary Outcomes (17)

• Clinical Global Impression of Improvement (CGI-I) Score

  At Week 8

• Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score

  Baseline and at Week 8

• 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

• Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score

  Baseline and at Week 8

• Change From Baseline in Sheehan Disability Scale (SDS) Scores

  Baseline and at Week 8

Study Arms (2)

NMRA-335140 (BTRX-335140)

EXPERIMENTAL

NMRA-335140 will be administered.

Drug: NMRA-335140

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

NMRA-335140 DRUG

Active Drug

Also known as: BTRX-335140

NMRA-335140 (BTRX-335140)

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if they meet all the following criteria:
• Are adult men or women between 18 to 65 years of age (inclusive) at informed consent
• Have a primary DSM-5 diagnosis of MDD, with prominent symptoms of anhedonia confirmed by Structured Clinical Interview for DSM-5 Disorders, Clinical Trials Version (SCID-5-CT)
• The current episode must have started at least 3 weeks prior to screening visit but no more than 12 months before the screening visit.
• Have not failed 2 or more courses of antidepressant treatment in the current episode
• Have no more than a 3-point change in HAMD 17 between screening and baseline
• Have sufficient history or an independent report to confirm that symptoms are causing functional impairment or clinically significant distress
• Meet the blinded rule list based on clinical scale criteria
• Have body mass index (BMI) between 18-40 kg/m2 (inclusive)
• Are medically stable (in the opinion of the investigator and Sponsor/Sponsors delegate) based on medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG) performed at screening and baseline
• Agree to the following birth control:
• Nonvasectomized men must agree to use a condom with spermicide, if sexually active during the study, until 90 days after the last dose of study drug administration. No restrictions are required for a vasectomized man, provided his vasectomy was performed 4 months or more prior to the first dose of study drug. A man who has been vasectomized less than 4 months prior to the first dose of study drug must follow the same restrictions as a nonvasectomized man. Additionally, men must refrain from sperm donation during study treatment and for at least 90 days following the last dose of study drug.
• Women of child-bearing potential (women not surgically sterilized and between menarche and 2 years postmenopausal) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at enrollment and agree to use reliable birth control (eg, oral contraceptives or Norplant®; a reliable double barrier method of birth control (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam); intrauterine devices; partner with vasectomy; or abstinence) during the study and for 10 days following the last dose of the study drug (BTRX-335140 or placebo). Women will be considered surgically sterile, if they have had tubal ligation, bilateral salpingo oophorectomy, or a hysterectomy.
• Note: Abstinence will be allowed if, in the investigator's judgement, it is determined that the participant is reliable, that abstinence is the preferred and usual lifestyle of the participant, and that abstinence will be continued for the duration of the study including the 10 days (women) or 90-day period (men) following last dose of study drug as noted above.
• Or engaged exclusively in a non-heterosexual relationship

You may not qualify if:

• Participants will be excluded from the study if they meet any of the following criteria:
• Have a history of any of the following DSM-5 disorders within the specified timeframe:
• Currently or in the past year: diagnosis of personality disorder, attention deficit disorder/attention deficit hyperactivity disorder, anorexia nervosa, or bulimia nervosa. Participants with comorbid generalized anxiety disorder, social anxiety disorder, or panic disorder for whom MDD is considered the primary diagnosis are not excluded.
• Lifetime: diagnosis of bipolar 1 or 2, schizophrenia, obsessive compulsive disorder, or post-traumatic stress disorder
• Have a history of substance or alcohol use disorder (AUD), per DSM-5 criteria, within the past year
• 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
• Have a history or signs of Cushing's disease, Addison's Disease, primary amenorrhea or other evidence of significant disorders of the hypothalamus-pituitary-adrenal axis
• Have any other clinically significant medical or psychiatric condition or circumstance prior to randomization that, in the opinion of the investigator, or Sponsor, could affect participant safety, preclude evaluation of response, interfere with the ability to comply with study procedures, or prohibit completion of the study, such as acute stress disorder, adjustment disorder, impulse control disorder, uncontrolled diabetes mellitus, renal or hepatic impairment, coronary artery disease, evidence of significant active cardiac, respiratory, or hematologic disease, cancer with \<5 year remission (basal cell carcinoma is not excluded), chronic pain, fibromyalgia, gastric bypass, lap band placement, or any other significant gastrointestinal condition
• Have had prior seizures (other than remote history of childhood febrile seizure) or other condition that would place the participant at increased risk of seizures or is taking anticonvulsants for seizure control
• Have a history of serious head injury (eg, skull fracture, cerebral contusion, or trauma resulting in prolonged unconsciousness), intracranial neoplasm, or hemorrhage
• Have ever had electroconvulsive treatment, vagal nerve stimulation, or treatment with ketamine or esketamine for MDD
• Have initiated transcranial magnetic stimulation, psychotherapy (such as Cognitive Behavioral Therapy) or have had a change in psychotherapy, or other non-drug therapies (such as acupuncture or hypnosis) within 4 weeks prior to Visit 1 (Screening) or at any time during the acute phase of the study
• Have a visual or physical motor impairment that could interfere with participant's ability to perform study assessments, as assessed by the investigator
• Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥2 x upper limit of normal (ULN) or a bilirubin level 1.5 x ULN unless due to a documented history of Gilbert's syndrome
• Have estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration \[CKD EPI\] 2009 creatinine equation at Visit 1 (Screening)

Sponsors & Collaborators

• Neumora Therapeutics, Inc.: lead

Study Sites (38)

Neumora Investigator Site

Phoenix, Arizona, 85016, United States

Location

Neumora Investigator Site

Bentonville, Arkansas, 72712, United States

Location

Neumora Investigator Site

Little Rock, Arkansas, 72211, United States

Location

Neumora Investigator Site

Bellflower, California, 90706, United States

Location

Neumora Investigator Site

Culver City, California, 90230, United States

Location

Neumora Investigator Site

Garden Grove, California, 92845, United States

Location

Neumora Investigator Site

Glendale, California, 91206, United States

Location

Neumora Investigator Site

Long Beach, California, 90807, United States

Location

Neumora Investigator Site

Oakland, California, 94607, United States

Location

Neumora Investigator Site

Riverside, California, 92506, United States

Location

Neumora Investigator Site

San Jose, California, 95124, United States

Location

Neumora Investigator Site

Santa Ana, California, 92705, United States

Location

Neumora Investigator Site

Sherman Oaks, California, 91403, United States

Location

Neumora Investigator Site

Torrance, California, 90502, United States

Location

Neumora Investigator Site

Upland, California, 91786, United States

Location

Neumora Investigator Site

Fernandina Beach, Florida, 32034, United States

Location

Neumora Investigator Site

Jacksonville, Florida, 32256, United States

Location

Neumora Investigator Site

Lauderhill, Florida, 33319, United States

Location

Neumora Investigator Site

Miami Lakes, Florida, 33016, United States

Location

Neumora Investigator Site

Orlando, Florida, 32751, United States

Location

Neumora Investigator Site

Orlando, Florida, 32801, United States

Location

Neumora Investigator Site

Sarasota, Florida, 34243, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30328, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30331, United States

Location

Neumora Investigator Site

Atlanta, Georgia, 30338, United States

Location

Neumora Investigator Site

Decatur, Georgia, 30030, United States

Location

Neumora Investigator Site

Las Vegas, Nevada, 89102, United States

Location

Neumora Investigator Site

Berlin, New Jersey, 08009, United States

Location

Neumora Investigator Site

Brooklyn, New York, 11229, United States

Location

Neumora Investigator Site

Jamaica, New York, 11432, United States

Location

Neumora Investigator Site

New York, New York, 10036, United States

Location

Neumora Investigator Site

Rochester, New York, 14618, United States

Location

Neumora Investigator Site

Staten Island, New York, 10312, United States

Location

Neumora Investigator Site

Dayton, Ohio, 45417, United States

Location

Neumora Investigator Site

Oklahoma City, Oklahoma, 73112, United States

Location

Neumora Investigator Site

Memphis, Tennessee, 38119, United States

Location

Neumora Investigator Site

Wichita Falls, Texas, 76309, United States

Location

Neumora Investigator Site

Clinton, Utah, 84015, United States

Location

Related Publications (1)

• Mathew SJ, Cutler AJ, Visitacion NC, Gold M, Yuan J, Aurora B. Navacaprant, a Novel and Highly Selective Kappa Opioid Receptor Antagonist, in Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial. J Clin Psychopharmacol. 2025 May-Jun 01;45(3):267-276. doi: 10.1097/JCP.0000000000001967. Epub 2025 Apr 9.

  PMID: 40199329 DERIVED

Related Links

• Mathew SJ, Cutler AJ, Visitacion NC, Gold M, Yuan J, Aurora B. Navacaprant, a Novel and Highly Selective Kappa Opioid Receptor Antagonist, in Adults with Major Depressive Disorder: A Randomized, Double-blind Phase 2 Clinical Trial. Journal of Clinical Ps

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

BTRX-335140

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Study Contact
• Organization: Neumora Therapeutics, Inc.

clinicaltrials@neumoratx.com

+1- (857) 760-0900

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 9, 2020
• Study Start: January 3, 2020
• Primary Completion: April 8, 2022
• Study Completion: June 23, 2022
• Last Updated: May 29, 2025
• Results First Posted: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (38)