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

Completed · Phase 2 · Has a placebo group

Conditions studied: Major Depressive Disorder

In brief

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.

Key facts

Study ID

NCT04221230

Run by

Neumora Therapeutics, Inc.

People needed

204

Starts

2020-01-03

Expected to finish

2022-06-23

Last updated by the study team

2025-05-29

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

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
• Willing and able to give written informed consent to participate
• Able to understand and comply with instructions in English
• Are judged by the investigator to be reliable and agree to keep all appointments for clinic visits, tests, and procedures, including venipuncture, and examinations required by the protocol

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)
• Have positive hepatitis C virus (HCV) antibody (Ab), hepatitis B surface antigen (HBs Ag), hepatitis A virus (HAV) IgM antibody (HAV-Ab [IgM]) or human immunodeficiency virus (HIV) test at Visit 1 (Screening)
• Have a thyroid-stimulating hormone (TSH) level of <0.9 x lower limit of normal (LLN) or >1.2 x ULN on or off stable treatment for hyperthyroidism or hypothyroidism; if TSH is abnormal, evaluate reflex Free T3 and Free T4. If reflex testing is normal, the assessment of normal thyroid function will be determined based on the judgement of the investigator, following discussion with the medical monitor.
• Have any other clinically significant abnormalities (significant would include laboratory deviations requiring acute medical intervention or further medical evaluation) in laboratory results at screening, including clinical chemistries, hematology, and urinalysis, and any clinical information that, in the judgment of the investigator or Sponsor, should preclude a participant's participation at study entry
• Have exclusionary ECG abnormalities obtained at Visit 1 (Screening) or Visit 2 (Baseline) that are QT interval corrected using Fridericia's formula (QTcF) >450 msec in males or >470 msec in females, complete bundle branch block, evidence of myocardial infarction or ischemia, and predominantly nonsinus conducted rhythms. Other abnormalities can be exclusionary at the discretion of the principal investigator or medical monitor. See Section 6.3.5 of protocol for guidance on ECG interpretations.
• Have a positive urine drug screen for amphetamines, barbiturates, cocaine, methadone, opioids, propoxyphene, tetrahydrocannabinol (THC), phencyclidine, or a positive blood alcohol level assessed by breathalyzer at Visit 1 (Screening) and Visit 2 (Baseline). For occasional (1 to 2 times per month maximum) cannabis users only, 1 retest is allowed and participant must agree to abstain from use for the duration of the study; a positive second test is exclusionary.
• Have any use, by history, of Salvinorin A
• Use of the following concomitant medications (contact the Sponsor-designated medical monitor to determine eligibility when in doubt):
• Psychoactive medication including stimulants, benzodiazepines and anxiolytics, oral antipsychotics, mood stabilizers/anticonvulsants (carbamazepine, lamotrigine, etc.), lithium, antidepressants, S adenosylmethionine, melatonin, agomelatine, and hypnotics/sedatives within 5 half-lives or 14 days (whichever is longer) of Visit 2 (Baseline)
• Fluoxetine and irreversible monoamine oxidase inhibitors within 4 weeks of Visit 2 (Baseline) depot antipsychotics within 2 months of Visit 2 (Baseline)
• Opioid agonists and antagonists

Where it is running

• Neumora Investigator Site — Phoenix, Arizona, United States
• Neumora Investigator Site — Bentonville, Arkansas, United States
• Neumora Investigator Site — Little Rock, Arkansas, United States
• Neumora Investigator Site — Bellflower, California, United States
• Neumora Investigator Site — Culver City, California, United States
• Neumora Investigator Site — Garden Grove, California, United States
• Neumora Investigator Site — Glendale, California, United States
• Neumora Investigator Site — Long Beach, California, United States
• Neumora Investigator Site — Oakland, California, United States
• Neumora Investigator Site — Riverside, California, United States
• Neumora Investigator Site — San Jose, California, United States
• Neumora Investigator Site — Santa Ana, California, United States
• Neumora Investigator Site — Sherman Oaks, California, United States
• Neumora Investigator Site — Torrance, California, United States
• Neumora Investigator Site — Upland, California, United States
• Neumora Investigator Site — Fernandina Beach, Florida, United States
• Neumora Investigator Site — Jacksonville, Florida, United States
• Neumora Investigator Site — Lauderhill, Florida, United States
• Neumora Investigator Site — Miami Lakes, Florida, United States
• Neumora Investigator Site — Orlando, Florida, United States
• Neumora Investigator Site — Orlando, Florida, United States
• Neumora Investigator Site — Sarasota, Florida, United States
• Neumora Investigator Site — Atlanta, Georgia, United States
• Neumora Investigator Site — Atlanta, Georgia, United States
• Neumora Investigator Site — Atlanta, Georgia, United States

Full record on ClinicalTrials.gov

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