CClinicalTrials.gg
CompletedNCT02459236Updated Sep 28, 2017

A Study of Intermittent Doses of CERC-301 in MDD

A Phase 2 interventional study of CERC-301 and Placebo in Major Depressive Disorder, sponsored by Avalo Therapeutics, Inc.. Completed at 13 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-09-28.

Sponsored by Avalo Therapeutics, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
115
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Major Depressive Disorder
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
115 participants (actual)

Study arms

  • Experimental
    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.

    Drug: CERC-301

  • Experimental
    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.

    Drug: CERC-301

  • Placebo comparator
    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.

    Drug: Placebo

Interventions

  • DrugCERC-301

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

  • DrugPlacebo
05

What researchers measure

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)

    Time frame: average of 2 and 4 days post-treatment

Secondary outcomes

  1. Change from baseline in Santen-7

    To evaluate the antidepressant effect of a single dose of CERC-301 (12 or 20 mg) compared to placebo averaged between 2 and 4 days post-treatment with study drug assessed by the 7-item unidimensional subset of the HDRS-17, the Santen-7

    Time frame: averaged between 2 and 4 days post treatment

  2. Change from baseline in HDRS-17

    To evaluate the antidepressant effect of a single dose of CERC-301 (12 or 20 mg) compared to placebo averaged between 2 and 4 days post-treatment with study drug assessed by the HDRS-17

    Time frame: averaged between 2 and 4 days post treatment

  3. Change from baseline in Bech-6

    To evaluate the antidepressant effect of CERC-301 at 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment assessed by the Bech-6.

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

  4. Change from baseline in Santen-7

    To evaluate the antidepressant effect of CERC-301 at 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment assessed by the Santen-7.

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

  5. Change from baseline in HDRS-17

    To evaluate the antidepressant effect of CERC-301 at 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment assessed by the HDRS-17.

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

  6. Change from baseline in CUDOS-A

    To evaluate the antidepressant effect of CERC-301 at 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment assessed by the Clinically Useful Depression Outcome Scale-Anxiety (CUDOS-A).

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

  7. Change from baseline in SHAPS-SR

    To evaluate the antidepressant effect of CERC-301 at 2, 4, 7 days after each dose, and 14 days after last dose of study drug treatment assessed by the Snaith-Hamilton Pleasure Scale Self Report (SHAPS-SR)

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

  8. Change from baseline in QIDS-SR

    To evaluate the antidepressant effect of CERC-301 at 7 days after each dose and 14 days after last dose of study drug treatment assessed by the Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR)

    Time frame: 7 days after each dose and 14 days after last dose of study drug treatment

  9. Change from baseline in CGI-I

    To evaluate the antidepressant effect of CERC-301 at 7 days after each dose and 14 days after last dose of study drug treatment assessed by the Clinical Global Impression-Improvement (CGI-I)

    Time frame: 7 days after each dose and 14 days after last dose of study drug treatment

  10. Change from baseline in CGI-S

    To evaluate the antidepressant effect of CERC-301 at 7 days after each dose and 14 days after last dose of study drug treatment assessed by the Clinical Global Impression -Severity (CGI-S)

    Time frame: 7 days after each dose and 14 days after last dose of study drug treatment

06

Study locations

13 sites
  • Pharmacology Research Institute (PRI)
    Newport Beach, California 92660, United States
  • Institute for Advanced Medical Research
    Alpharetta, Georgia 30005, United States
  • Chicago Research Center, Inc.
    Chicago, Illinois 60634, United States
  • Alexian Brothers Center for Psychiatric Research
    Hoffman Estates, Illinois 60169, United States
  • Psychiatric Care and Research Center
    O'Fallon, Missouri 63368, United States
  • Bioscience Research LLC
    Mount Kisco, New York 10549, United States
  • The Medical Research Network, LLC
    New York, New York 10128, United States
  • Fingerlakes Clinical Research
    Rochester, New York 14618, United States
  • Richmond Behavioral Associates
    Staten Island, New York 10312, United States
  • Summit Research Network (Oregon) Inc.
    Portland, Oregon 97201, United States
  • Lehigh Center for Clinical Research
    Allentown, Pennsylvania 18104, United States
  • Research Strategies of Memphis, LLC
    Memphis, Tennessee 38119, United States
  • Northwest Clinical Research Center
    Bellevue, Washington 98007, United States
07

Registry details

Key details

Study ID
NCT02459236
Lead sponsor
Avalo Therapeutics, Inc.
Responsible party
Sponsor
First posted
Jun 2, 2015
Start date
Jun 2015
Primary completion
Sep 2016
Completion
Dec 2016
Last update
Sep 28, 2017

Study contacts

Ronald N Marcus, MD
study director · Avalo Therapeutics, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion