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

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03538522
• Other study ID #: NeuroActiva
• Status: Completed
• Phase: Phase 2
• Start date: September 15, 2018
• Est. completion date: October 30, 2019

Study information

• Verified date: November 2019
• Source: NeuroActiva, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study seeks to evaluate the efficacy and safety of NA-83 in subjects with mild cognitive impairment due to Alzheimer's Disease

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: October 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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 ? 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.

Related Conditions & MeSH terms

• Alzheimer Dementia
• Alzheimer Disease
• Cognition Disorders
• Cognitive Disorder
• Cognitive Dysfunction
• Cognitive Impairment
• Dementia
• Dementia With Lewy Bodies
• Dementia, Vascular
• Disease
• Lewy Body Disease
• Mild Cognitive Impairment
• Neurocognitive Disorders
• Neurodegenerative Diseases
• Tauopathies

Intervention

Drug:
• N-831(Traneurocin) 10 mg QD
Oral administration of 10 mg capsule of NA-831 QD for 24 weeks
• NA-831 (Traneurocin) 20 mg QD
Oral administration of 20 mg capsule of NA-831 QD for 24 weeks
• NA-831 (Traneurocin) 40 mg QD
Oral administration of 40 mg capsule of NA-831 QD or for 24 weeks
• Placebo oral capsule QD
Oral administration of oral placebo capsule QD or 24 weeks

Locations

Country	Name	City	State
New Zealand	NeuroActiva Testing Facility of NeuroActiva (New Zealand) Ltd	Auckland
New Zealand	NeuroActiva-Clinical Research Unit	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
NeuroActiva, Inc.

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 24
Secondary	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.	Week 24
Secondary	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.	Week 24