A Phase 2 Study of Zelquistinel or Placebo for the Reduction of Symptoms of Major Depressive Disorder

What this study is about

The goal of this clinical trial is to learn if zelquistinel works to treat depression in adults. It will also learn about the safety of zelquistinel. The main questions it aims to answer are: Does zelquistinel reduce depression scores in participants compared to participants who take a placebo (a look-alike tablet that contains no zelquistinel1)? What medical problems are observed in participants who take zelquistinel? Participants will take one tablet of zelquistinel or placebo every week for 6 weeks. Participants will visit the clinic every week of the 6 week period to have the severity of their depression evaluated.

Who can join (things the study team will check)

✅ You may be able to join if…

• Male or female subject.
• Aged 18 to 64 years, inclusive.
• Subject has a first episode or recurrent episode diagnosis of MDD, defined by the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), ≥3 weeks and ≤18 months. The diagnosis of MDD will be made by a central rater using the Structured Clinical Interview for DSM-5 Clinical Trials version (SCID-5-CT).
• Subject has a HDRS-17 total score of ≥18 at the Screening Visit (V1) and Baseline Visit (V2) as assessed by a central rater, with no more than a 25% change from the Screening Visit (V1) to the Baseline Visit (V2)
• Subject has HARS total score ≥15 at the Screening Visit (V1) and predose at the Baseline Visit (V2), AND
• Subject has ISI total score ≥10 at the Screening Visit (V1) and predose at the Baseline Visit (V2).
• Female subjects must meet 1 of the following:
  • Surgically sterile or at least 2 years menopausal (ie, postmenopausal is defined as a woman with the absence of menses for at least 12 consecutive months). Menopausal status is to be confirmed by assessing the follicle stimulating hormone level at Screening Visit (V1), or,
  • If a woman of childbearing potential, subject must use an acceptable method of birth control from date of Screening to the last evaluation at Day 71. Must have a documented negative point of care urine pregnancy test within 24 hours prior to first dosing.
• Male subjects, including those who are surgically sterile, must use a medically acceptable form of contraception from the time of randomization until the End of Week 6 Visit. Male subjects are strongly advised to inform female partners of the need for them to use highly effective birth control during this time period.
• Ability to understand the nature and requirements of the study and is willing to comply with the study restrictions and agree to return for the required assessments.
• Provides written informed consent to participate in the study.
• Is able to communicate with investigational site personnel, able to complete patient-reported outcome measures and in the opinion of the Investigator, can be reliably rated on assessment scales.
• Have an appropriate severity of illness of at least moderately ill corresponding to a CGI-S score of ≥4 at the Screening and Baseline Visits (V1 and V2, respectively), as assessed by a central rater.

🚫 You may not be able to join if…

• A subject who meets any of the following criteria will be excluded from study participation:
• Evidence of treatment-resistant MDD, defined by having an inadequate response (≤25%) to 2 or more different medications approved for the treatment of MDD at an adequate dose (per locally approved label) for an adequate duration during the current episode using the Massachusetts General Hospital Antidepressant Treatment Rating Questionnaire (MGH ATRQ) assessed by a site rater.
• Current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, obsessive compulsive disorder, borderline personality disorder,attention-deficit/ hyperactivity disorder, post-traumatic stress disorder, or panic attacks. Subjects not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded.
• Subject has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features.
• Subject has a score of >4 on the CADSS at the Screening Visit (V1).
• Active seizure disorder.
• Traumatic brain injury with current signs or symptoms.
• Treatment with esketamine or ketamine, any psychedelic agent, or any experimental agent being evaluated to treat depression, whether as an antidepressant or for other use, within the past 12 months. o Treatment with any other experimental agents not used to treat depression within the past 3 months.
• Concomitant treatment with other Food and Drug Administration (FDA)-approved antidepressants or adjuvant agents or enhancers such as dextromethorphan, antipsychotics, mood stabilizers, sedatives, stimulants, or benzodiazepines. Subject must discontinue concomitant treatment at least 14 days prior to the Baseline Visit. o Subjects may continue anxiolytic agents, except for drugs that are also used to treat depression. Subjects may continue sleep aids, so long as they have been on a stable dose for at least 3 months and do not intend to change dose during the Double-Blind Treatment Period (Week 1 [Day 1] through End of Week 6). However, trazodone must be discontinued for at least 14 days prior to the Baseline Visit.
• Use of cannabis or cannabis-derived molecules, including tetrahydrocannabinol (THC), whether natural or chemically-synthesized, including hemp seed oil and cannabidiol (CBD) products (eg, gummies). Subject must discontinue the use of such products at least 14 days prior to the Baseline Visit, and THC must be below the limit of detection at the Baseline Visit.
• Positive test for any drug of abuse.
• Treated with any medical device or digital therapeutics for MDD, anxiety, insomnia, or other CNS indications within 90 days of screening in this study.
• History of electroconvulsive therapy, vagus nerve stimulation, deep brain stimulation, or repetitive transcranial magnetic stimulation within the past 5 years or has had a failure of response to electroconvulsive therapy at any time.
• Subject has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate (eGFR) <70 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration-creatinine (CKD-EPI creatinine) methodology.
• Subject has liver protein and enzyme (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, total bilirubin, lactate dehydrogenase) test result >1.5 × upper limit of normal (subjects with a diagnosis of Gilbert's Syndrome may be eligible if no liver function or enzyme test results other than total bilirubin are >1.5 × upper limit of normal).
• Subject has resting radial pulse rate (supine) <60 or >100 bpm at the Screening Visit or predose Baseline, based on a single assessment.
• Subject has resting diastolic blood pressure <50 mmHg at the Screening Visit or predose Baseline.
• Subject has PR interval >250 msec at the Screening Visit or predose Baseline, or QT corrected for heart rate by Fridericia's formula (QTcF) or QT corrected for heart rate by Bazett's formula (QTcB) interval >450 msec in males or >470 msec in females, or QRS interval >120 msec, based on a single reading.
• Evidence of alcohol abuse (>4 units of alcohol on most days; 1 unit=½ pint of beer, 1 glass of wine, or 1 ounce of hard liquor/spirits) or a positive saliva alcohol screen at Screening and predose at the Baseline Visit. Alcohol consumption should be avoided for at least 24 hours prior to Baseline Visit.
• Abuse of illicit substances by DSM-5 definition of substance use disorder within the 12 months prior to the Screening Visit.

+ 16 more criteria — see the full checklist in the app.

Where this trial is running

• NoesisPharma, LLC, Phoenix, Arizona, United States
• Del Sol Research Management, Tucson, Arizona, United States
• Catalina Research Institute, LLC, Montclair, California, United States
• Excell Research, Inc, Oceanside, California, United States
• Anderson Clinical Research, Redlands, California, United States
• Studyops Inc, San Francisco, California, United States
• Lumos Clinical Research Center, San Jose, California, United States
• Sunwise Clinical Research, Walnut Creek, California, United States
• Clinical Neuroscience Solutions, Inc, Jacksonville, Florida, United States
• Premier Clinical Research Institute Inc, Miami, Florida, United States
• Aqualane Clinical Research, Naples, Florida, United States
• EquiPath Health and Research Tampa Bay, LLC, Riverview, Florida, United States

+ 20 more sites.

Who to contact

Karen Raudibaugh · 781-786-1545 · karen.raudibaugh@syndeio.bio

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT07115329.