Clinical trial NCT01941043: A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation Despite Antidepressant Treatment
Official title: A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation 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: 2013-09-13
Enrollment: 1357
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current study will evaluate the antidepressant effect of CERC-301 during 28 days of treatment in subjects with MDD who are currently experiencing a severe depressive episode despite stable ongoing treatment with selective serotonin- or serotonin-norepinephrine reuptake inhibitors (SSRI or SNRI). The study population will be enriched for subjects that would benefit most from rapid onset, those with recent active suicidal ideation, but not a risk to themselves or others and are deemed appropriate for an out-patient study with careful safety surveillance. This will allow the study to focus on the antidepressant effects of CERC-301 but also explore effects on suicidal ideation. To explore rapid onset, the primary endpoint will be at 7 days, but effects over the 28 days of treatment will be examined as a secondary endpoint.


Eligibility criteria: Inclusion Criteria:

1. Male or female 18 to 70 years of age inclusive.
2. Females must be either:

   1. Post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile -or-
   2. Women of childbearing potential (WOCBP) meeting the criteria below:

   i. Uses an acceptable double-barrier method of contraception as determined by the Investigator -and- ii. Is not lactating, has a negative serum beta human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test prior to randomization on Day 0.
3. Male subjects must agree to use a condom if partner is of childbearing potential.
4. Diagnosis of MDD recurrent without psychotic features according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria with diagnosis confirmed using the Structured Clinical Interview for DSM-IV Axis I Disorders Clinical Trials Version (SCID-CT).
5. Currently adhering to antidepressant drug regimen that consists of stable SSRI or SNRI therapy
6. Inadequate antidepressant response to current antidepressant therapy despite adequate dose and duration
7. HDRS-17 score ≥ 21 on the HDRS-17 performed by the site at screening
8. Recent active suicidal ideation defined as a score of 2 on the intensity of ideation section on the Columbia-Suicide Severity Rating Scale (C-SSRS) during the four weeks prior to screening using the "Baseline/Screening" version of the C-SSRS.
9. In otherwise good general health without any unstable medical conditions (as determined by medical history, physical examination, 12-lead ECG, clinical laboratory testing, etc.).

Exclusion Criteria:

1. History of substance abuse or dependence within the 3 months prior to screening.
2. Positive urine drug test at screening and prior to randomization on Day 0 unless due to a permitted medication that is documented in the subject's medication history.
3. Positive ethanol breath test at screening and/or prior to randomization on Day 0.
4. Elevated semi-recumbent blood pressure at screening and prior to randomization on Day 0, defined as systolic blood pressure \> 140 mm Hg and diastolic blood pressure
5. 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, unstable angina, coronary artery disease, congestive heart failure, etc.).
6. Subjects with clinical laboratory test abnormality deemed clinically significant by the Investigator at screening.
7. Axis I diagnosis of obsessive compulsive disorder, posttraumatic stress disorder, bipolar I or II mood disorders, eating disorders (e.g., anorexia nervosa, bulimia nervosa), psychotic disorders (e.g., schizoaffective disorder, schizophrenia), significant cognitive disorders (e.g., delirium, dementia, amnesia), or dissociative disorders.
8. Subjects with Axis II diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder.
9. Subjects with a neurologic disorder that could cause or contribute to depression (e.g., Alzheimer's disease, Parkinson's disease).
10. Female subjects currently experiencing postpartum depression.
11. Subjects who, in the opinion of the Investigator, are not appropriate for a 35-day placebo-controlled study due to risk of significant threat to self or others during screening or study conduct.
12. Use of other NMDA-receptor modulators (e.g., dextromethorphan, ketamine, amantadine, memantine) within 30 days of screening and throughout the study.
13. The following concomitant medication use is excluded within six weeks prior to screening:

    * Bupropion or tricyclic antidepressants
    * Intermittent, symptomatic use of benzodiazepines (e.g. symptomatic treatment of anxiety or panic attacks)
    * Antipsychotics
    * Lithium
    * Any medications known to directly interact with central or peripheral serotonergic receptors, other than the permitted antidepressants.
    * Any medications known to directly interact with central noradrenergic receptors, other than the permitted antidepressants.
14. Electroconvulsive therapy, transcranial magnetic stimulation, or vagal nerve stimulation during the current depressive episode.
15. Participation in an investigational drug or device study within the 6 months prior to screening.
16. Subjects with suicidal behavior within 6 months prior to screening as measured by the C-SSRS "Baseline/Screening" version.
17. Subjects with a C-SSRS score \> 2 on the intensity of ideation section at randomization (Visit 2a), using the "Since Last Visit" version of the C-SSRS.

Primary outcomes:
measure: HDRS-17 after 7 days of dosing with study drug
timeFrame: Screening & Days 0, 4, 7, 11, 14, 21,28, & 35
Secondary outcomes:
measure: HDRS-17 Averaged between 7 and 28 days of treatment with study drug
timeFrame: Screening, Days 0, 4, 7, 11, 14, 21, 28, & 35
measure: HDRS-17 after 28 days of dosing with study drug
timeFrame: Screening, Days 0, 4, 7, 11, 14, 21, 28, 35
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona TMS Therapy Center
state: Arizona
city: Culver City
country: United States
facility: ProScience Research Group
state: California
city: Garden Grove
country: United States
facility: Collaborative NeuroScience Network, Inc.
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists
state: California
city: National City
country: United States
facility: Synergy Clinical Research Center
state: California
city: Oakland
country: United States
facility: Pacific Clinical Trials, LLC
state: California
city: Oceanside
country: United States
facility: Southern CA Psychiatrists
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Chicago
country: United States
facility: Chicago Psychiatry Associates
state: Illinois
city: Baltimore
country: United States
facility: Sheppard Pratt Health System
state: Maryland
city: O'Fallon
country: United States
facility: PCRC
state: Missouri
city: Mount Kisco
country: United States
facility: Bioscience Research
state: New York
city: New York
country: United States
facility: The Medical Research Network
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas
state: Texas
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
Study officials:
affiliation: Avalo Therapeutics, Inc.
name: James Vornov, MD, PhD
role: STUDY_DIRECTOR
References: