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

• Sponsor: Neuralstem Inc. (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT02724735
• Collaborator: (none)
• Enrollment: 220
• Locations: 12
• Duration (Months): 17
• Patients Per Site: 18.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	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 Design

• Study Type: Observational
• Anticipated Enrollment: 220 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Longitudinal Observational Cohort Study of NSI-189, a Neurogenic Compound Among Out-Patients With Major Depressive Disorder
• Study Start Date: Aug 1, 2016
• Anticipated Primary Completion Date: Dec 1, 2017
• Anticipated Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Primary Objective: Durability of Effect defined as the time until the start of a new antidepressant treatment (ADT) [6 months]

   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).

Secondary Outcome Measures

1. Montgomery-Asberg Depression Rating Scale (MADRS) [6 months]

   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.

2. Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR) [6 months]

   Compare the continued antidepressant efficacy of NSI-189 with that of placebo.

3. Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ) [6 months]

   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.

4. Cogscreen Battery [6 months]

   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.

5. Symptoms of Depression Questionnaire (SDQ) [6 months]

   Compare the continued efficacy of NSI-189 with that of placebo, as measured by the Symptoms of Depression Questionnaire (SDQ)

6. Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) [6 months]

   Characterize the safety and tolerability of NSI-189, compared to placebo.

7. The Columbia Suicide Severity Rating Scale (C-SSRS) [6 months]

   Characterize the safety and tolerability of NSI-189, compared to placebo.

8. 17-item Hamilton Depression Rating Scale (HAMD17) [6 months]

   HAMD17 will be used to characterize the safety and tolerability of NSI-189, compared to placebo.

9. Discontinuation rates [6 months]

   Characterize the safety and tolerability of NSI-189, compared to placebo.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 61 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Garden Grove	California	United States	92845
2		National City	California	United States	91950
3		Denver	Colorado	United States	80209
4		Jacksonville	Florida	United States	32256
5		Orlando	Florida	United States	32801
6		Alpharetta	Georgia	United States	30005
7		St. Louis	Missouri	United States	63141
8		Staten Island	New York	United States	10312
9		Dayton	Ohio	United States	45417
10		Memphis	Tennessee	United States	38119
11		Dallas	Texas	United States	75231
12		San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Neuralstem Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Neuralstem Inc.
• ClinicalTrials.gov Identifier: NCT02724735
• Other Study ID Numbers: NS2015-2
• First Posted: Mar 31, 2016
• Last Update Posted: Sep 21, 2016
• Last Verified: Sep 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Neuralstem Inc.: Depression; Major Depressive Disorder (MDD); Major Depressive Disorder; Neurogenesis; Synaptogenesis; NSI-189; Neuralstem
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

No Results Posted as of Sep 21, 2016