A Study of Intermittent Doses of CERC-301 in MDD

NCT02459236 | Completed Phase 2

• 1 other identifier: Clin301-203
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 13

Brief Summary

There is a significant unmet medical need for rapidly acting treatment of subjects with severe major depressive disorder (MDD) who have not adequately responded to antidepressant therapy. Alternative therapies require weeks to achieve full efficacy, may have significant side effects, and still fail in a high percentage of subjects. Rapid reduction of severe depression by pharmacological therapy is important to reduce the need for hospitalization and risk of self-harm and mortality. CERC-301, a highly selective, orally bioavailable, N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B), also referred to as Glutamate NMDA receptor subunit epsilon-2 (GluN2B) antagonist, would be a therapeutic breakthrough if it provides rapid onset of antidepressant effects and an effect size similar to that seen with experimental intravenous NMDA modulators.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Bech-6 from baseline

  To evaluate the antidepressant effect of CERC-301 (12 or 20 mg) compared to placebo averaged between 2 and 4 days post-treatment with study drug assessed by the 6-item unidimensional subset (Bech-6) of the 17-item Hamilton Depression Rating Scale (HDRS-17)

  average of 2 and 4 days post-treatment

Secondary Outcomes (10)

• Change from baseline in Santen-7

  averaged between 2 and 4 days post treatment

• Change from baseline in HDRS-17

  averaged between 2 and 4 days post treatment

• Change from baseline in Bech-6

  2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment

• Change from baseline in Santen-7

  2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment

• Change from baseline in HDRS-17

  2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment

Study Arms (3)

CERC-301 12mg

EXPERIMENTAL

The study includes two dose administrations 7 days apart (Day 0 and Day 7) followed by 14 days of observation for a total of 21 days.

Drug: CERC-301

CERC-301 20mg

EXPERIMENTAL

The study includes two dose administrations 7 days apart (Day 0 and Day 7) followed by 14 days of observation for a total of 21 days.

Drug: CERC-301

Placebo

PLACEBO COMPARATOR

The study includes two dose administrations 7 days apart (Day 0 and Day 7) followed by 14 days of observation for a total of 21 days.

Drug: Placebo

Interventions

CERC-301 DRUG

CERC-301, a highly selective, orally bioavailable, NMDA receptor subunit 2B (NR2B), also referred to as Glutamate NMDA receptor subunit epsilon-2 (GluN2B) antagonist

CERC-301 12mg; CERC-301 20mg

Placebo DRUG

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:

• Diagnosis of MDD recurrent without psychotic features according to DSM-IV-TR criteria with diagnosis confirmed using the Structured Clinical Interview for DSM-IV Axis I Disorders Clinical Trials Version (SCID-CT).
• Lifetime history of ≥2 major depressive episodes, for which at least one required treatment with SSRI or SNRI antidepressants.
• History during the current major depressive episode of failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms) to ≤3 treatment courses of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration during the current episode, according to the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire.

You may not qualify if:

• Duration of current depression episode ≥2 years or diagnosis of Persistent Depressive Disorder (DSM-V) or Dysthymic Disorder (DSM-IV)
• Use of other NMDA-receptor modulators (e.g., dextromethorphan, ketamine, amantadine, memantine) within 30 days of screening and throughout the study.
• History of use of an NMDA-receptor modulator for the treatment of MDD.
• Use of bupropion, tricyclic antidepressants, antipsychotics, stimulants, or lithium within 8 weeks prior to screening
• Initiation of psychotherapy or a change in intensity of psychotherapy or other non-drug therapies (e.g., hypnosis, acupuncture) within 8 weeks prior to screening.
• Electroconvulsive therapy, transcranial magnetic stimulation, or vagal nerve stimulation during the current depressive episode.
• Excessive alcohol use, which is defined by the Centers for Disease Control as \>1 drink per day for women and \>2 drinks per day for men.
• Current diagnosis of a Substance Use (including alcohol) Disorder (Abuse or Dependence, as defined by DSM-IV/V), with the exception of nicotine dependence, at screening or within 6 months prior to screening.
• Active, comorbid disease that might limit the ability of the subject to participate in the study as determined by the Investigator (i.e., poorly controlled diabetes mellitus, congestive heart failure, etc.).
• Current neurologic or neuropsychiatric disorder which could interfere with the ability to diagnose or assess MDD or which could cause or contribute to depressive symptomatology (e.g., Alzheimer's disease, Parkinson's diseases, chronic pain syndromes, including fibromyalgia, substance use disorder, post-partum depression).
• Lifetime history of the following disorders: Bipolar I, II, or Not Otherwise Specified (NOS) mood disorders, eating disorders , schizophrenia and other psychotic disorders, sleep disorders , significant cognitive disorders, dissociative disorders, impulse control disorders, and borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorders.
• Subjects with suicidal behavior within 6 months prior to screening as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) "Baseline/Screening" version.
• Elevated seated blood pressure at screening and prior to randomization
• Lifetime history of stroke or congestive heart failure, atrial fibrillation or coronary artery disease.
• Clinically significant current liver disease or liver enzyme (GGT, ALT, AST, total bilirubin) elevations at screening above 2 × the ULN.

Sponsors & Collaborators

• Avalo Therapeutics, Inc.: lead

Study Sites (13)

Pharmacology Research Institute (PRI)

Newport Beach, California, 92660, United States

Location

Institute for Advanced Medical Research

Alpharetta, Georgia, 30005, United States

Location

Chicago Research Center, Inc.

Chicago, Illinois, 60634, United States

Location

Alexian Brothers Center for Psychiatric Research

Hoffman Estates, Illinois, 60169, United States

Location

Psychiatric Care and Research Center

O'Fallon, Missouri, 63368, United States

Location

Bioscience Research LLC

Mount Kisco, New York, 10549, United States

Location

The Medical Research Network, LLC

New York, New York, 10128, United States

Location

Fingerlakes Clinical Research

Rochester, New York, 14618, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Summit Research Network (Oregon) Inc.

Portland, Oregon, 97201, United States

Location

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

Research Strategies of Memphis, LLC

Memphis, Tennessee, 38119, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Ronald N Marcus, MD

  Avalo Therapeutics, Inc.

  STUDY DIRECTOR

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: May 27, 2015
• First Posted: June 2, 2015
• Study Start: June 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 28, 2017

Record last verified: 2017-09

Locations

US (13)