A Longitudinal Observational Cohort Study of NSI-189, With Out-Patients With Major Depressive Disorder

A Longitudinal Observational Cohort Study of NSI-189, a Neurogenic Compound Among Out-Patients With Major Depressive Disorder

All subjects completing the randomized treatment period in Protocol NS2014-1 will discontinue study drug and be asked to provide consent to be followed in this 6-month study, at their final safety visit. The study will consist of an enrollment visit, followed by bi-monthly in-clinic visits with monthly telephone visits between in-clinic visits.

Study Overview

• Status: Unknown
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: NSI-189

Detailed Description

Following completion of the NS2014-1 final study visit procedures, Subjects will be offered the opportunity to enroll in this longitudinal observational cohort protocol to monitor their depression and to assess durability of effect and long-term safety of NSI-189.

The Enrollment Visit begins when informed consent is signed.The duration of the follow-up period will be up to 6 months, until the start of a new antidepressant treatment. Subjects who provide consent will be seen for in-person visits every 8 weeks, with bi-monthly phone visits occurring between in-person visits. Safety assessments and efficacy assessments will be performed at each visit. No study drug will be taken during the Longitudinal Observational Cohort study.

• Study Type: Observational
• Enrollment (Anticipated): 220

Contacts and Locations

• Study Contact: Name: Karl Johe, Ph.D.; Email: NSI-189MDD@neuralstem.com

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92845
      • Recruiting
    • National City, California, United States, 91950
      • Recruiting
  • Colorado
    • Denver, Colorado, United States, 80209
      • Recruiting
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Recruiting
    • Orlando, Florida, United States, 32801
      • Recruiting
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Recruiting
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Recruiting
  • New York
    • Staten Island, New York, United States, 10312
      • Recruiting
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Recruiting
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Recruiting
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
    • San Antonio, Texas, United States, 78229
      • Recruiting

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 61 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects having completed the randomized treatment period under the NS2014-1 clinical study protocol.

Description

Inclusion Criteria:

1. 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.
2. Subject completed the 12-week randomized treatment period and final study visit for the NS2014-1 clinical study.

Exclusion Criteria:

1. Subjects taking excluded medications.
2. Subject who, in the opinion of the Site Investigator, are unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope and possible consequences of the clinical study.
3. Subject who, in the opinion of the Site Investigator, are unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude, inability to return for follow-up and improbability of completing the clinical study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Longitudinal Observational Cohort; Following completion of the NS2014-1 final study visit procedures, Subjects will be offered the opportunity to enroll in this longitudinal observational cohort protocol to monitor their depression and to assess durability of effect and long-term safety of NSI-189.	Drug: NSI-189; 0 Milligrams, 40 Milligrams or 80 Milligrams administered in the acute study only; Other Names: NSI-189 Phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective: Durability of Effect defined as the time until the start of a new antidepressant treatment (ADT)	The primary objective is to determine the durability of effect of NSI-189 phosphate compared to placebo in subjects with Major Depressive Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5TH EDITION). Durability of effect is defined as the time until the start of a new antidepressant treatment (ADT).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)	Compare the continued Montgomery-Asberg Depression Rating Scale (MADRS) response and remission rates of subjects treated with NSI-189 to those of subjects assigned to placebo. Response is defined as a 50% or greater reduction from baseline to endpoint on the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Remission is defined as an endpoint MADRS total score of 10. The duration of 50% or greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) total score sustained following treatment will be noted.	6 months
Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR)	Compare the continued antidepressant efficacy of NSI-189 with that of placebo.	6 months
Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ)	Evaluate the continued efficacy of NSI-189 compared to placebo on the cognitive aspects associated with Major Depressive Disorder, and the onset and duration of improvement.	6 months
Cogscreen Battery	Evaluate the continued efficacy of NSI-189 compared to placebo on the cognitive aspects associated with Major Depressive Disorder, and the onset and duration of improvement.	6 months
Symptoms of Depression Questionnaire (SDQ)	Compare the continued efficacy of NSI-189 with that of placebo, as measured by the Symptoms of Depression Questionnaire (SDQ)	6 months
Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI)	Characterize the safety and tolerability of NSI-189, compared to placebo.	6 months
The Columbia Suicide Severity Rating Scale (C-SSRS)	Characterize the safety and tolerability of NSI-189, compared to placebo.	6 months
17-item Hamilton Depression Rating Scale (HAMD17)	HAMD17 will be used to characterize the safety and tolerability of NSI-189, compared to placebo.	6 months
Discontinuation rates	Characterize the safety and tolerability of NSI-189, compared to placebo.	6 months

Collaborators and Investigators

• Sponsor: Neuralstem Inc.
• Investigators: Study Director: Karl Johe, Ph.D., Neuralstem Inc.

Publications and helpful links

General Publications

• 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. Erratum In: Mol Psychiatry. 2016 Oct;21(10):1483-4.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: March 15, 2016
• First Submitted That Met QC Criteria: March 25, 2016
• First Posted (Estimate): March 31, 2016

Study Record Updates

• Last Update Posted (Estimate): September 21, 2016
• Last Update Submitted That Met QC Criteria: September 20, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Depression; Neurogenesis; Major Depressive Disorder; Major Depressive Disorder (MDD); Synaptogenesis; NSI-189; Neuralstem
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: NS2015-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes