Clinical trial NCT02459236: A Study of Intermittent Doses of CERC-301 in MDD
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of Intermittent Doses of CERC-301 in the Treatment of Subjects With Severe Depression Despite Antidepressant Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: Avalo Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-02
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Lifetime history of ≥2 major depressive episodes, for which at least one required treatment with SSRI or SNRI antidepressants.
3. 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:

1. Duration of current depression episode ≥2 years or diagnosis of Persistent Depressive Disorder (DSM-V) or Dysthymic Disorder (DSM-IV)
2. Use of other NMDA-receptor modulators (e.g., dextromethorphan, ketamine, amantadine, memantine) within 30 days of screening and throughout the study.
3. History of use of an NMDA-receptor modulator for the treatment of MDD.
4. Use of bupropion, tricyclic antidepressants, antipsychotics, stimulants, or lithium within 8 weeks prior to screening
5. 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.
6. Electroconvulsive therapy, transcranial magnetic stimulation, or vagal nerve stimulation during the current depressive episode.
7. 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.
8. 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.
9. 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.).
10. 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).
11. 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.
12. Subjects with suicidal behavior within 6 months prior to screening as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) "Baseline/Screening" version.
13. Elevated seated blood pressure at screening and prior to randomization
14. Lifetime history of stroke or congestive heart failure, atrial fibrillation or coronary artery disease.
15. Clinically significant current liver disease or liver enzyme (GGT, ALT, AST, total bilirubin) elevations at screening above 2 × the ULN.
16. Clinically significant renal impairment defined as estimated creatinine clearance \[CrCl\] \<50 mL/min at screening measured using Cockcroft-Gault formula.
17. Fasting serum glucose \>140 mg/dL.
18. Subjects who, in the opinion of the Investigator, are not appropriate for a 21-day placebo-controlled study due to risk of significant threat to self or others during screening or study conduct.
19. Previous participation in an investigational study using CERC-301.
20. Participation in an investigational drug or device study within the 6 months prior to screening.

Primary outcomes:
measure: Change in Bech-6 from baseline
timeFrame: average of 2 and 4 days post-treatment
Secondary outcomes:
measure: Change from baseline in Santen-7
timeFrame: averaged between 2 and 4 days post treatment
measure: Change from baseline in HDRS-17
timeFrame: averaged between 2 and 4 days post treatment
measure: Change from baseline in Bech-6
timeFrame: 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment
measure: Change from baseline in Santen-7
timeFrame: 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment
measure: Change from baseline in HDRS-17
timeFrame: 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment
measure: Change from baseline in CUDOS-A
timeFrame: 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment
measure: Change from baseline in SHAPS-SR
timeFrame: 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment
measure: Change from baseline in QIDS-SR
timeFrame: 7 days after each dose and 14 days after last dose of study drug treatment
measure: Change from baseline in CGI-I
timeFrame: 7 days after each dose and 14 days after last dose of study drug treatment
measure: Change from baseline in CGI-S
timeFrame: 7 days after each dose and 14 days after last dose of study drug treatment
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Pharmacology Research Institute (PRI)
state: California
city: Alpharetta
country: United States
facility: Institute for Advanced Medical Research
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center, Inc.
state: Illinois
city: Hoffman Estates
country: United States
facility: Alexian Brothers Center for Psychiatric Research
state: Illinois
city: O'Fallon
country: United States
facility: Psychiatric Care and Research Center
state: Missouri
city: Mount Kisco
country: United States
facility: Bioscience Research LLC
state: New York
city: New York
country: United States
facility: The Medical Research Network, LLC
state: New York
city: Rochester
country: United States
facility: Fingerlakes Clinical Research
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
Study officials:
affiliation: Avalo Therapeutics, Inc.
name: Ronald N Marcus, MD
role: STUDY_DIRECTOR
References: