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A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831

Primary Purpose

Mild Cognitive Impairment, Alzheimer Disease, Alzheimer Dementia

Status
Completed
Phase
Phase 2
Locations
New Zealand
Study Type
Interventional
Intervention
N-831(Traneurocin) 10 mg QD
NA-831 (Traneurocin) 20 mg QD
NA-831 (Traneurocin) 40 mg QD
Placebo oral capsule QD
Sponsored by
NeuroActiva, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Mild Cognitive Impairment

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION

  1. Is male or female, at 55-85 years of age (inclusive) at screening self-reported memory complaint, corroborated by spouse or companion as appropriate.
  2. Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score ≤ 5.
  3. Mini-Mental State Exam (MMSE) ≥23
  4. Center for Epidemiologic Studies-Depression (CES-D) score <27.
  5. Normal thyroid function, defined as TSH, T3 and T4 within normal limits.
  6. Agree not to consume alcoholic beverages within 8 hours of each study visit.
  7. Willing and able to sign informed consent and complete the CTB and all other tests and procedures as listed in the protocol.
  8. Able to read at a 6th grade level or equivalent
  9. Female subjects must be surgically sterile or post-menopausal for at least 2 years. If <2 years post-menopausal, then a follicle stimulating hormone (FSH) ≥40 mIU/mL must be obtained.
  10. If participant is receiving an acetylcholinesterase inhibitor or memantine, the dose must have been stable for at least three months before Screening
  11. Must have a reliable and competent trial partner/informant who has a close relationship with the participant and is willing to accompany the participant to all required trial visits, and to monitor compliance of the administration of the trial medication

EXCLUSION CRITERIA

  1. Subjects who have any significant, untreated psychiatric illness or any CNS condition (such as schizophrenia, Parkinson's disease, stroke, etc.) that could interfere with the study evaluations or procedures or which poses an additional risk.
  2. Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  3. History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
  4. Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
  5. History of seizures or epilepsy within the last 5 years
  6. History of hepatitis or liver disease that has been active within the 6 months prior toScreening
  7. History of malignancy occurring within the 5 years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma
  8. Clinically significant vitamin B12 or folate deficiency in the 6 months before Screening
  9. History of unstable angina, myocardial infarction, chronic heart failure or clinically significant conduction abnormalities within 1 year prior to Screening Visit
  10. History of alcohol or substance abuse or dependence within the past year.
  11. Has human immunodeficiency virus (HIV) by medical history
  12. Acute infective sinusitis.
  13. History or presence of an abnormality of the external or internal structures of the nose or nasopharynx, except for surgical correction of the nasal septum or a "broken nose" at least 2 years previously, or surgical repair of cleft palate when <30 years of age.
  14. Use of medications that are known to cause frank obtundation of cognition
  15. History of or current significant systemic disease judged to interfere with the study evaluations or likely to be a safety concern.
  16. Untreated sleep apnea or treatment for sleep apnea for <3 months.
  17. Clinically significant systemic illness or serious infection within 30 days prior to or during the screening period
  18. Use of allowed medications for chronic conditions at doses that have not been stable for at least 4 weeks prior to Screening, or use of AD medications at doses that have not been stable for at least 8 weeks prior to Screening
  19. Abnormal clinical laboratory test results, specifically: Alanine transaminase (ALT) or aspartate transaminase (AST) >2 х the upper limit of normal (ULN),Hematology <80% the lower limit of normal, Creatinine ≥2 mg/dL and ,Other clinical laboratory values or vital signs considered clinically significant in the opinion of the Investigator.
  20. Treatment with any investigational drug, biologic, or device within the previous 30 days prior to screening.
  21. Surgery involving general anesthesia within the past 3 months or planned surgery requiring general anesthesia during the study period.
  22. Contraindications to study procedures
  23. Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participants at higher risk for adverse events (AEs), or impair the participant's ability to perform cognitive testing or complete study procedures.

Sites / Locations

  • NeuroActiva-Clinical Research Unit
  • NeuroActiva Testing Facility of NeuroActiva (New Zealand) Ltd

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Low-dose N-831(Traneurocin)- 10 mg QD

Medium-dose NA-831(Traneurocin)- 20 mg QD

High-dose NA-831(Traneurocin)- 40 mg QD

Placebo

Arm Description

Oral administration of 10 mg of NA-831 (Traneurocin) per day for 24 weeks

Oral administration of 20 mg of NA-831(Traneurocin) per day for 24 weeks

Oral administration of 40 mg of NA-831(Traneurocin) per day for 24 weeks

Oral administration of placebo per day for 24 weeks

Outcomes

Primary Outcome Measures

Change from baseline in Clinical Dementia Rating Scale- Sum of Boxes (CDR-SB) score at Week 24
To study to the change from baseline in the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score at Week 2 and Week 24. The CDR-SB is obtained through interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18 with the higher values represent worse outcome.

Secondary Outcome Measures

1. Mean difference between the last (Week 24) and first (Week 2) postdose using Clinical Dementia Rating Scale- Sum of Boxes (CDR-SB) assessment
To assess the Clinical Dementia Rating Scale- Sum of Boxes (CDR-SB) mean difference between the Week 2 and Week 24. The CDR-SB is obtained through interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values represent worse outcome.
Assess the change from baseline in ADCS-ADL MCI at Week 24
Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL MCI) at Week 24. The Galasko method for Alzheimer Disease Cooperative Study (ADCS) will be used, which contains 23 items covering physical and mental functioning and independence in self-care. For Activities of Daily Living (ADLs), the scoring used was the following: 0 = no impairment, 1 = problem performing but no supervision or assistance needed, 2 = problem requiring supervision, 3 = problem with assistance needed, and 4 = unable to perform. The scores range from 0 to 78, with higher values indicates greater disability.

Full Information

First Posted
March 16, 2018
Last Updated
June 26, 2020
Sponsor
NeuroActiva, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03538522
Brief Title
A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831
Official Title
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of NA-831 in Alzheimer Patients With Mild Cognitive Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
September 15, 2018 (Actual)
Primary Completion Date
September 30, 2019 (Actual)
Study Completion Date
October 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NeuroActiva, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study seeks to evaluate the efficacy and safety of NA-83 in subjects with mild cognitive impairment due to Alzheimer's Disease
Detailed Description
Mild cognitive impairment ("MCI") is defined as the "symptomatic pre-dementia stage" on the continuum of cognitive decline. Currently, no medications have proven effective for MCI. Preclinical experiments indicate that NA-831 is an endogenous small molecule that exhibits neuroprotection, neurogenesis, and cognitive protective properties across a range of disease models. NA-831 has been shown to be safe and well tolerated in healthy volunteers. This study seeks to evaluate the efficacy and safety of NA-83 in 126 subjects with mild cognitive impairment due to Alzheimer's Disease

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Alzheimer Disease, Alzheimer Dementia, Dementia, Vascular, Dementia With Lewy Bodies, Cognitive Impairment, Tauopathies, Neurodegenerative Diseases, Neurocognitive Disorders, Cognitive Disorder

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
126 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low-dose N-831(Traneurocin)- 10 mg QD
Arm Type
Experimental
Arm Description
Oral administration of 10 mg of NA-831 (Traneurocin) per day for 24 weeks
Arm Title
Medium-dose NA-831(Traneurocin)- 20 mg QD
Arm Type
Experimental
Arm Description
Oral administration of 20 mg of NA-831(Traneurocin) per day for 24 weeks
Arm Title
High-dose NA-831(Traneurocin)- 40 mg QD
Arm Type
Experimental
Arm Description
Oral administration of 40 mg of NA-831(Traneurocin) per day for 24 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral administration of placebo per day for 24 weeks
Intervention Type
Drug
Intervention Name(s)
N-831(Traneurocin) 10 mg QD
Intervention Description
Oral administration of 10 mg capsule of NA-831 QD for 24 weeks
Intervention Type
Drug
Intervention Name(s)
NA-831 (Traneurocin) 20 mg QD
Intervention Description
Oral administration of 20 mg capsule of NA-831 QD for 24 weeks
Intervention Type
Drug
Intervention Name(s)
NA-831 (Traneurocin) 40 mg QD
Intervention Description
Oral administration of 40 mg capsule of NA-831 QD or for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule QD
Intervention Description
Oral administration of oral placebo capsule QD or 24 weeks
Primary Outcome Measure Information:
Title
Change from baseline in Clinical Dementia Rating Scale- Sum of Boxes (CDR-SB) score at Week 24
Description
To study to the change from baseline in the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score at Week 2 and Week 24. The CDR-SB is obtained through interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18 with the higher values represent worse outcome.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
1. Mean difference between the last (Week 24) and first (Week 2) postdose using Clinical Dementia Rating Scale- Sum of Boxes (CDR-SB) assessment
Description
To assess the Clinical Dementia Rating Scale- Sum of Boxes (CDR-SB) mean difference between the Week 2 and Week 24. The CDR-SB is obtained through interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values represent worse outcome.
Time Frame
Week 24
Title
Assess the change from baseline in ADCS-ADL MCI at Week 24
Description
Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL MCI) at Week 24. The Galasko method for Alzheimer Disease Cooperative Study (ADCS) will be used, which contains 23 items covering physical and mental functioning and independence in self-care. For Activities of Daily Living (ADLs), the scoring used was the following: 0 = no impairment, 1 = problem performing but no supervision or assistance needed, 2 = problem requiring supervision, 3 = problem with assistance needed, and 4 = unable to perform. The scores range from 0 to 78, with higher values indicates greater disability.
Time Frame
Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION Is male or female, at 55-85 years of age (inclusive) at screening self-reported memory complaint, corroborated by spouse or companion as appropriate. Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score ≤ 5. Mini-Mental State Exam (MMSE) ≥23 Center for Epidemiologic Studies-Depression (CES-D) score <27. Normal thyroid function, defined as TSH, T3 and T4 within normal limits. Agree not to consume alcoholic beverages within 8 hours of each study visit. Willing and able to sign informed consent and complete the CTB and all other tests and procedures as listed in the protocol. Able to read at a 6th grade level or equivalent Female subjects must be surgically sterile or post-menopausal for at least 2 years. If <2 years post-menopausal, then a follicle stimulating hormone (FSH) ≥40 mIU/mL must be obtained. If participant is receiving an acetylcholinesterase inhibitor or memantine, the dose must have been stable for at least three months before Screening Must have a reliable and competent trial partner/informant who has a close relationship with the participant and is willing to accompany the participant to all required trial visits, and to monitor compliance of the administration of the trial medication EXCLUSION CRITERIA Subjects who have any significant, untreated psychiatric illness or any CNS condition (such as schizophrenia, Parkinson's disease, stroke, etc.) that could interfere with the study evaluations or procedures or which poses an additional risk. Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year History of seizures or epilepsy within the last 5 years History of hepatitis or liver disease that has been active within the 6 months prior toScreening History of malignancy occurring within the 5 years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma Clinically significant vitamin B12 or folate deficiency in the 6 months before Screening History of unstable angina, myocardial infarction, chronic heart failure or clinically significant conduction abnormalities within 1 year prior to Screening Visit History of alcohol or substance abuse or dependence within the past year. Has human immunodeficiency virus (HIV) by medical history Acute infective sinusitis. History or presence of an abnormality of the external or internal structures of the nose or nasopharynx, except for surgical correction of the nasal septum or a "broken nose" at least 2 years previously, or surgical repair of cleft palate when <30 years of age. Use of medications that are known to cause frank obtundation of cognition History of or current significant systemic disease judged to interfere with the study evaluations or likely to be a safety concern. Untreated sleep apnea or treatment for sleep apnea for <3 months. Clinically significant systemic illness or serious infection within 30 days prior to or during the screening period Use of allowed medications for chronic conditions at doses that have not been stable for at least 4 weeks prior to Screening, or use of AD medications at doses that have not been stable for at least 8 weeks prior to Screening Abnormal clinical laboratory test results, specifically: Alanine transaminase (ALT) or aspartate transaminase (AST) >2 х the upper limit of normal (ULN),Hematology <80% the lower limit of normal, Creatinine ≥2 mg/dL and ,Other clinical laboratory values or vital signs considered clinically significant in the opinion of the Investigator. Treatment with any investigational drug, biologic, or device within the previous 30 days prior to screening. Surgery involving general anesthesia within the past 3 months or planned surgery requiring general anesthesia during the study period. Contraindications to study procedures Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participants at higher risk for adverse events (AEs), or impair the participant's ability to perform cognitive testing or complete study procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lloyd Tran, PhD
Organizational Affiliation
NeuroActiva, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
NeuroActiva-Clinical Research Unit
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
NeuroActiva Testing Facility of NeuroActiva (New Zealand) Ltd
City
Auckland
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831

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