A Randomized, Double-Blind, Placebo-Controlled Study of Intermittent Doses of CERC-301 in the Treatment of Subjects With Severe Depression Despite Antidepressant Treatment
Overview
- Phase
- Phase 2
- Intervention
- CERC-301
- Conditions
- Major Depressive Disorder
- Sponsor
- Avalo Therapeutics, Inc.
- Enrollment
- 115
- Locations
- 13
- Primary Endpoint
- Change in Bech-6 from baseline
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Detailed Description
The study will evaluate the antidepressant effect of one or two administrations of two doses of CERC-301 (12 mg and 20 mg) in subjects with MDD who are currently experiencing a severe depressive episode despite stable ongoing treatment with a selective serotonin- or serotonin-norepinephrine reuptake inhibitor (SSRI or SNRI).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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).
Arms & Interventions
CERC-301 12mg
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.
Intervention: CERC-301
CERC-301 20mg
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.
Intervention: CERC-301
Placebo
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Change in Bech-6 from baseline
Time Frame: average of 2 and 4 days post-treatment
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)
Secondary Outcomes
- 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)
- 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 CUDOS-A(2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment)
- Change from baseline in SHAPS-SR(2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment)
- Change from baseline in QIDS-SR(7 days after each dose and 14 days after last dose of study drug treatment)
- Change from baseline in CGI-S(7 days after each dose and 14 days after last dose of study drug treatment)
- Change from baseline in CGI-I(7 days after each dose and 14 days after last dose of study drug treatment)