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A Phase 3 Study of NE3107 in Probable Alzheimer's Disease

Sponsor
BioVie Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04669028
Collaborator
(none)
316
Enrollment
36
Locations
2
Arms
16.9
Anticipated Duration (Months)
8.8
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

U.S. multicenter, parallel group study designed to evaluate the safety and efficacy of oral 20 mg twice daily (BID) NE3107 vs placebo in 316 adult subjects with mild to moderate probable AD. Two coprimary outcome measures (the Alzheimer's Disease Assessment Scale Cognitive Subscale 12 [ADAS Cog12] and the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS CGIC] will be evaluated as the change from Baseline to Week 30. Secondary endpoints include measures of neuropsychological deficits, functional performance, and glycemic control. A subset of patients may volunteer for exploratory magnetic resonance imaging (volumetric changes) and positron emission tomography (cortical glucose metabolic rate) scans at baseline and week 30.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
316 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Double Blind, Randomized, Placebo Controlled, Parallel Group, Multicenter Study of NE3107 in Subjects Who Have Mild to Moderate Probable Alzheimer's Disease
Actual Study Start Date :
Aug 5, 2021
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Jan 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: NE3107

Hard gelatin capsule containing 20 mg micronized NE3107 drug substance blended with common excipients for oral formulations

Drug: NE3107
NE3107 is an investigational orally bioavailable, blood-brain barrier permeable anti-inflammatory agent with a new mechanism of action targeting multiple mechanisms of pathology in Alzheimer's disease.
Placebo Comparator: placebo

Hard gelatin capsule containing only common excipients for oral formulations

Drug: Placebo
capsules that do not contain NE3107

Outcome Measures

Primary Outcome Measures

  1. Change in Alzheimer's Disease Assessment Scale Cognitive Subscale 12 [ADAS Cog12] [baseline and week 30 (end of study)]

    series of questions to measure cognitive function, score 0-70, 0 = no impairment, 70 = most severe impairment

  2. Change in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS CGIC] [baseline and week 30 (end of study)]

    series of questions to measure cognitive functional and behavioral characteristics scored 1-7 with 1 being greatest improvement and 7 being most severe worsening of disease

Secondary Outcome Measures

  1. Alzheimer's Disease Cooperative Study Activities of Daily Living Scale [baseline and week 30 (end of study)]

    23 item scale with total score of 0-78, with a lower score indicating worse disease

  2. Mini Mental State Exam (MMSE) [baseline and week 30 (end of study)]

    30 questions with a total score of 0-30, with a lower score indicating worse disease

  3. Neuropsychiatric Index 12 [baseline and week 30 (end of study)]

    12 questions with total score 0-12, with higher score indicating worse disease

  4. Alzheimer's Disease clinical COMposite Score (ADCOMS) [baseline and week 30 (end of study)]

    composite score of questions from different cognitive test. total score ranges from 0-1.97, with higher scores indicating worse disease

  5. Homeostatic assessment of insulin resistance 2 (HOMA2-IR) [baseline and week 30 (end of study)]

    blood tests for insulin and glucose levels

  6. fasting blood glucose [baseline and week 30 (end of study)]

  7. postprandial glucose excursions [baseline and week 30 (end of study)]

    3-day average of postprandial glucose measure by continuous glucose monitoring

Other Outcome Measures

  1. Resource Utilization in Dementia (short version, Lite) [baseline and week 30 (end of study)]

    compiles data on the use of social services, frequency and duration of hospitalizations, unscheduled contacts with health care professionals, use of concomitant medications by both the caregiver and the patient, amount of time the caregiver spends caring for the patient and missing work, and patients' use of study medication.

  2. volumetric magnetic resonance imaging (vMRI) [baseline and week 30 (end of study)]

  3. cortical metabolic rate using fluorodeoxyglucose positron emission [baseline and week 30 (end of study)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
60 Years to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
    1. Male or female subject aged 60 to 85 y at Screening (V1). 2. Has mild to moderate probable AD as defined by all of the following criteria:

  1. Meets the National Institute on Aging and Alzheimer's Association (NIA-AA, 2011) criteria of all cause dementia and probable AD.

  2. Has a Clinical Dementia Rating (CDR) (Section 8.1.6) Standard Global Score of 1 to 2, inclusive (mild to moderate).

  3. Has a MMSE score of ≥14 and ≤24 at both Screening and Baseline visits. The difference in scores between Screening and Baseline must be < 3 points (i.e., the difference must not exceed 3 points). (Section 8.1.5)

  4. Has an historical MRI or CT scan of the brain on file no earlier than AD diagnosis that fails to exhibit features of another potential pathobiology that could better account for the cognitive disorder.

  5. Historical evidence of impairment on a mental status exam or documented prior diagnosis of or treatment for dementia from a health care professional.

  6. Has a modified Hachinski Ischemic Scale (Section 8.1.8) score of ≤4 at Screening (V1).

  7. If taking an anticholinesterase inhibitor (AChEI) (e.g., donepezil, galantamine, rivastigmine) and/or memantine at Screening (V1):

  8. Must have been taking the medication(s) for ≥3 mo, and

  9. Current dose regimen and form must have remained stable for ≥6 wk and must remain stable throughout participation in the study.

NOTE: Subjects not being treated with an AChEI and/or memantine at Screening (V1) may also be enrolled if initiation of an AChEI and/or memantine is not planned for the time period during which the subject will be participating in this study.

NOTE: Dosage changes during the study due to clinical deterioration should be discussed with the Medical Monitor prior to being implemented.

  1. If taking medications for glycemic control at the time of Screening (V1), must be stable on the current dose regimen and form for ≥3 mo prior to randomization and must remain stable throughout participation in the study.

  2. Females taking hormone replacement therapy (HRT) must have maintained a stable regimen for at least two years prior to randomization and agree to continue the regimen until completing the final safety assessment in Week 30 at the end of the study.

  3. Must meet one of the following criteria:

  4. Females: Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy, or tubal ligation) for at least 6 mo prior to Screening (V1) or postmenopausal (postmenopausal females must have no menstrual bleeding for at least 1 y; if needed, the Investigator may confirm menopausal status through an FSH assessment at Screening [V1]). 6.8.1

  5. Males: Vasectomized. If not vasectomized, must use an appropriate contraception method as noted in Section 6.8.1.

  6. Must provide voluntary written informed consent prior to Screening (V1). If the subject is unable to provide informed consent due to cognitive status, the subject must provide assent and a legally authorized representative provides full written informed consent on behalf of the subject.

  7. Willing to allow collection of blood for ApoE genotyping. 11. Able to comply with the study procedures, in the opinion of the Investigator.

  8. Has a primary caregiver/study partner willing to accept responsibility for supervising the treatment (e.g., administering study drug), accompanying the subject to clinic visits and assessing the condition of the subject throughout the study in accordance with all protocol requirements. The primary caregiver/study partner must be willing to sign the caregiver ICF.

Exclusion Criteria:
    1. Has prior brain imaging inconsistent with probable AD 2. A history of a stroke that resulted in a cognitive or motor deficit or, MRI or CT evidence of a moderate or large cerebral infarct.

  1. Should there be any evidence of neurologic symptoms between the date of the scan confirming diagnosis and Screening (V1), rescanning is necessary.

  2. Has clinically relevant abnormal laboratory tests including serum vitamin B12 deficiency, thyroid function abnormality, severe anemia, or electrolyte abnormality.

  3. Diagnosis of type 1 diabetes or type 2 diabetes requiring insulin treatment or the need to use continuous glucose monitoring. Subjects who become insulin dependent during the study may not continue to participate in the study.

  4. History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within 12 mo prior to Screening (V1).

  5. Subjects are ineligible, if in the opinion of the investigator, they have deficits in speech, comprehension, auditory functioning, or vision which would adversely impact their ability to perform the study's cognitive test procedures, complete rating scales, or engage in interviews.

  6. Has any of the following laboratory findings at Screening (V1):

  7. Alanine aminotransferase >3 × upper limit of normal (ULN), aspartate aminotransferase >3 × ULN, or history of clinically significant liver disease in the Investigator's medical judgment.

  8. Hemoglobin ≤10 g/dL.

  9. International normalized ratio >1.5 if not on anticoagulant medication; if the subject is on anticoagulant medication, the anticoagulant medication should be optimized and on a stable dose for ≥4 wk prior to Screening (V1).

  10. Creatinine clearance (Cockcroft Gault formula) of <45 mL/min.

  11. Known to be seropositive for human immunodeficiency virus (1 and 2), hepatitis B, or hepatitis C. Subjects with hepatitis C who had spontaneous resolution or received successful curative treatment (e.g., HARVONI® [ledipasvir/sofosbuvir]) with a documentation of undetectable viral load for at least 3 mo may be allowed. Serological testing will not be performed as part of this study.

  12. Female subjects with child-bearing potential (premenopausal, menstrual bleeding within the last 12 months) or who are pregnant or breastfeeding.

  13. History of any medical illness such as cancer requiring systemic therapy in the last 5 y, except for localized basal cell carcinoma of the skin, in situ cervical cancer successfully treated with surgical excision, and stable (for ≥90 d prior to Screening [V1]) prostate cancer.

  14. History of breast cancer. 11. History of severe heart failure (Grade 2 or higher on the New York Heart Association scale), major stroke, uncontrolled seizure disorder, or other medical illness that, in the Investigator's opinion, will increase the subject's risk of participation in the study or confound study assessments.

  15. Any surgery requiring general anesthesia that is planned to occur during the study. Local anesthesia during outpatient surgery is permitted if, in the opinion of the Investigator, the operation will not interfere with study procedures and subject safety.

  16. History or current evidence of major psychiatric illness such as schizophrenia, bipolar disorder, or major depressive disorder that may interfere with the subject's ability to perform the study and all assessments.

  17. Geriatric Depression Scale Short Form (GDS SF) score >8 at Screening (V1). NOTE: Mild depression or depressive mood arising in the context of AD are not criteria for exclusion. The use of anti epileptic medication for non-seizure-related treatment or the use of antidepressants is allowed if the dose has remained stable for ≥60 d prior Screening (V1).

  18. Violent or aggressive behavior that may interfere with study participation

  19. History of active suicidal thoughts (Type 4 or 5 on the C SSRS) in the 6 mo prior to Screening (V1) or at Baseline (V2), history of a suicide attempt in the previous 2 y or >1 lifetime suicide attempt, or are at serious suicide risk, in the Investigator's clinical judgment.

  20. History of alcohol or drug abuse or dependence within 24 mo of Screening (V1) as defined by the Diagnostic and Statistical Manual of Mental Disorders 5.

  21. Positive urine screen for drugs of abuse that include methadone, cocaine, and amphetamines; positive urine screen for opiates, barbiturates, or benzodiazepines without a prescription.

  22. Has participated in another Investigational New Drug research study involving small molecule drugs within 60 d or biological drugs within 90 d prior to the first dose of study drug in this study (Baseline [V2]) or within 5 half-lives of the other investigational medicinal product, whichever is longer.

  23. History of Covid-19 (SARS-CoV-2) infection within 6-weeks prior to screening. Subjects with unresolved symptoms of Covid-19 infection or ongoing cognitive or other deficits attributable to post-Covid-19, that may affect participant safety or interfere with efficacy assessments, based on the Investigator's clinical judgment.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Perseverance Research Center Scottsdale Arizona United States 85254
2 Clinical Endpoints Scottsdale Arizona United States 85258
3 Tucson Neuroscience Research Tucson Arizona United States 85710
4 WR-PRI Encino California United States 91316
5 WR-PRI Newport Beach California United States 92660
6 Cordova Clinical Research Sacramento California United States 95841
7 Integrity Clinical Research, LLC Doral Florida United States 33122
8 Reliable Clinical Reseach Hialeah Florida United States 33012
9 Galiz Research Hialeah Florida United States 33016
10 Charter Research Lady Lake Florida United States 32159
11 Accel Research-Lakeland Clinical Research Unit Lakeland Florida United States 33803
12 Accel Research Sites-Maitland Clinical Research Unit Maitland Florida United States 32751
13 Accel Research Sites Maitland Florida United States 32751
14 Life Medical Research Group Miami Gardens Florida United States 33014
15 South Florida Research Phase I-IV Miami Springs Florida United States 33166
16 LMG Research Miami Florida United States 33125
17 Ocean Clinical Research Miami Florida United States 33126
18 Future Care Solution Miami Florida United States 33165
19 EZY Medical Research Miami Florida United States 33176
20 Coral Research Clinic Miami Florida United States 33186
21 Nuovida Research Center Miami Florida United States 33186
22 New York Neurology Associates New York Florida United States 10003
23 Adaptive Clinical Research, Inc. North Miami Florida United States 33161
24 ClinCloud Viera Florida United States 32940
25 Conquest Research, LLC Winter Park Florida United States 32789
26 AMITA Health Alexian Brothers Medical Center Elk Grove Village Illinois United States 60007
27 Clinical Research Center of Nevada Las Vegas Nevada United States 89106
28 Advanced Clinical Institute Neptune New Jersey United States 07753
29 Bio Behavioral Health Toms River New Jersey United States 08755
30 Richmond Behavioral Associates Staten Island New York United States 10312
31 Richmond Behavioral Associates Staten Island New York United States 10312
32 AMC Research Charlotte North Carolina United States 28105
33 The Ohio State University Columbus Ohio United States 43210
34 KCA Neurology Franklin Tennessee United States 37067
35 KCA Neurology Franklin Tennessee United States 37067
36 Memory Clinic Bennington Vermont United States 05201

Sponsors and Collaborators

  • BioVie Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
BioVie Inc.
ClinicalTrials.gov Identifier:
NCT04669028
Other Study ID Numbers:
  • NM101
First Posted:
Dec 16, 2020
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Alzheimer Disease

Study Results

No Results Posted as of Aug 23, 2022