Study of NSI-189 for Major Depressive Disorder

NCT02695472 | Unknown Phase 2 DMC

• 1 other identifier: NS2014-1
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 13

Brief Summary

The study will consist of a screening period and a randomized treatment. Approximately 220 subjects who meet eligibility during the screening period will be randomized to initiate a 12-week, double-blind treatment with NSI-189 80 milligrams/day (provided as 40 milligrams twice per day), NSI-189 40 milligrams once a day, or placebo.

Conditions

Major Depressive Disorder

Keywords

Depression; Major Depressive Disorder (MDD); Major Depressive Disorder; Neurogenesis; Synaptogenesis; NSI-189; Neuralstem

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Up to 12 weeks

Secondary Outcomes (6)

• Symptoms of Depression Questionnaire (SDQ)

  Up to 12 weeks

• The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ)

  Up to 12 weeks

• 17-item Hamilton Rating Scale for Depression (HAMD17)

  Up to 12 weeks

• Clinical Global Impressions - Severity and Improvement (CGI-S, CGI-I)

  Up to 12 weeks

• Cogstate Brief Battery

  Up to 12 weeks

Study Arms (3)

Placebo Arm

PLACEBO COMPARATOR

One Placebo tablet, twice daily

Drug: Placebo

40 Milligrams NSI-189, total dose daily

EXPERIMENTAL

One 40 Milligrams NSI-189 tablet and 1 placebo tablet per day

Drug: Placebo; Drug: 40 Milligrams NSI-189

80 Milligrams NSI-189, total dose daily

EXPERIMENTAL

One 40 Milligrams NSI-189 tablet twice per day

Drug: 80 Milligrams NSI-189

Interventions

80 Milligrams NSI-189 DRUG

Orally Administered

Also known as: NSI-189 twice per day (BID)

80 Milligrams NSI-189, total dose daily

Placebo DRUG

Orally administered

40 Milligrams NSI-189, total dose daily; Placebo Arm

40 Milligrams NSI-189 DRUG

Orally Administered

Also known as: NSI-189 Once a day (QD)

40 Milligrams NSI-189, total dose daily

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has the ability to understand the purpose, potential benefits and risks of the study and to provide signed and dated informed consent, authorizing the use of protected health information in accordance with national and local Subject privacy regulations.
• Males and females 18 to 60 years of age, inclusive, at the time of informed consent.
• Diagnosis of major depressive disorder, recurrent, as per Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and confirmed by Structured Clinical Interview for the Diagnostic and Statistical Manual specific for Clinical Trials. Their major depressive episode must be at least 8 weeks in duration and confirmed via Structured Clinical Interview for the Diagnostic and Statistical Manual mood module interview administered by a remote, independent raters, prior to the baseline visit.
• Montgomery-Asberg Depression Scale (MADRS) score of 20 or greater, at Screening and Baseline (MADRS score confirmed to be 20 or greater via remote SAFER interview by an independent rater prior to the baseline visit).
• The following applies to female Subjects: Non-pregnant, non-lactating females of childbearing potential are eligible as long as they agree to use a double barrier method of birth control from Screening until 3 months following discontinuation of IP. Women who are not of childbearing potential (bilateral oophorectomy, bilateral tubal ligation, hysterectomy, or post-menopausal for at least 1 year) will not require such parameters in order to be eligible.
• The following applies to male subjects: Male subjects with a female partner of childbearing potential will be required to use double barrier method of birth control or practice abstinence during this study and for 3 months following discontinuation of Investigational Product. Note: These requirements also apply for male subjects who have had a vasectomy.
• Body mass index (BMI) ≥19.5 and ≤38.0 kg/m2, at Screening. Bodyweight must be \>50 kg.
• Of stable medical health, in the opinion of the Site Investigator, as determined by Investigator discretion (medical history, physical examination, vital signs, ECG, and clinical laboratory assessments).

You may not qualify if:

• Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or other major disease as determined by the Investigator or designee such that participation in the study would place subjects at increased risk for serious adverse events.
• History of cancer or malignancy within the last 5 years. Note: Subjects with basal or squamous cell carcinoma may be permitted into the study on a case by case basis.
• History of seizures; head trauma; or any clinically significant finding on the neurologic examination such that participation in the study would place subjects at increased risk for serious adverse events.
• Previous or current diagnosis of bipolar or schizoaffective disorder or psychotic disorder, or any psychotic symptoms during the current major depressive episode (according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition).
• Subjects who have a concurrent primary psychiatric diagnosis, diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th edition, other than depression.
• Subjects with delirium, dementia, Parkinson's disease, or Huntington's disease.
• Subjects who have failed to respond to more than two antidepressant trials of adequate dose (as defined in Massachusetts General Hospital Antidepressant Treatment Response) and duration (at least 8 weeks in duration) during the current major depressive episode as determined by the local rater and confirmed by an independent, remote rater prior to the baseline visit.
• Subjects with clinically significant suicidal ideation and/or behavior currently as determined by the Site Investigator, such that participation in the study would place subjects at increased risk for serious adverse events.
• Subjects with any current homicidal ideation.
• Clinically significant abnormal clinical chemistry values, as determined by the Site Investigator, or any values for Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin or creatinine that are 1.5 times above the upper limit of normal (ULN) and deemed clinically significant by the Site Investigator; any clinically significant values as determined by the Site Investigator for platelets or hemoglobin that are below the lower limit of normal (LLN); or any out of normal range values for white blood cells (WBC) deemed clinically significant by the Site Investigator.
• Clinically significant (as determined by the Investigator) 12-lead Electrocardiogram (ECG) abnormalities, including corrected QT interval using Bazett's correction method of \>450 msec for males and \>470 msec for females.
• Subjects with (current) severe Post-Traumatic Stress Disorder (PTSD), severe Obsessive Compulsive Disorder (OCD), severe binge eating disorder, or subjects with anorexia or bulimia nervosa active within the past three years.
• Subjects who plan to undergo elective invasive procedures/surgeries at any time during the study through End-of-study.
• Subjects taking excluded medications (See Appendix 1)..
• History of alcohol or drug-dependence or abuse by Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and confirmed by Structured Clinical Interview for the Diagnostic and Statistical Manual specific for Clinical Trials within 12 months prior to Screening.

Sponsors & Collaborators

• Neuralstem Inc.: lead

Study Sites (13)

Collaborative Neuroscience Network, LLC

Garden Grove, California, 92845, United States

Location

Synergy San Diego

National City, California, 91950, United States

Location

Clinical Trials of the Rockies

Denver, Colorado, 80209, United States

Location

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

Location

Clinical Neuroscience Solutions, Inc

Orlando, Florida, 32801, United States

Location

Institute for Advanced Medical Research

Alpharetta, Georgia, 30005, United States

Location

Psychiatric Medicine Associates, LLC

Skokie, Illinois, 60076, United States

Location

St. Louis Clinical Trials, LC

St Louis, Missouri, 63141, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Midwest Clinical Research Center, LLC

Dayton, Ohio, 45417, United States

Location

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

FutureSearch Trials of Dallas

Dallas, Texas, 75231, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Fava M, Johe K, Ereshefsky L, Gertsik LG, English BA, Bilello JA, Thurmond LM, Johnstone J, Dickerson BC, Makris N, Hoeppner BB, Flynn M, Mischoulon D, Kinrys G, Freeman MP. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2016 Oct;21(10):1372-80. doi: 10.1038/mp.2015.178. Epub 2015 Dec 8.

  PMID: 26643541 BACKGROUND

• Tajiri N, Quach DM, Kaneko Y, Wu S, Lee D, Lam T, Hayama KL, Hazel TG, Johe K, Wu MC, Borlongan CV. NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats. J Cell Physiol. 2017 Oct;232(10):2731-2740. doi: 10.1002/jcp.25847. Epub 2017 Apr 25.

  PMID: 28181668 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

BID protein, human

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Karl Johe, Ph.D.

  Neuralstem Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: March 1, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 24, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share

Locations

US (13)