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

NCT04669028 | Completed Phase 3 FDA Drug

• 1 other identifier: NM101
• Study Type: interventional
• Target: 439
• Locations: 1 country
• Sites: 1

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 400 adult subjects with mild to moderate probable AD. Dual co-primary endpoints (Clinical Dementia Rating Scale Sum of Boxes, CDR-SB and ADAS-Cog12) will be evaluated as the change from Baseline to Week 30. Secondary endpoints include measures of cognition, 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)

  test of 6 cognitive or functional domains, including memory, orientation, judgment, community affairs, home hobbies, and personal care are scored by certified raters after interviewing both participants and their informants. Higher score is indicative of more severe disease. The minimum score is 0 and the maximum score is 18. The CDR-SB is a co-primary outcome with ADAS-Cog12

  baseline and week 30 (end of study)

• Change in Alzheimer's Disease Assessment Scale Cognitive Subscale 12 [ADAS Cog12]

  The ADAS-Cog was developed to assess the level of cognitive dysfunction in Alzheimer's disease. It is also used in studies of interventions in people with mild cognitive impairment. It is also used for assessing the efficacy of antidementia treatments. The test is administered and scored by a certified rater to assess the cognitive domains of memory, language, orientation and praxis. A higher score is indicative of more severe disease, with 0 (no cognitive deficit) being the lowest score possible and 80 being the highest score and associated with severe cognitive impairment. ADAS-Cog12 is a co-primary outcome with CDR-SB.

  baseline and week 30 (end of study)

Secondary Outcomes (6)

• Alzheimer's Disease clinical COMposite Score (ADCOMS)

  baseline and week 30 (end of study)

• Alzheimer's Disease Cooperative Study Activities of Daily Living Scale

  baseline and week 30 (end of study)

• Mini Mental State Exam (MMSE)

  baseline and week 30 (end of study)

• Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS CGIC]

  baseline and week 30 (end of study)

• Neuropsychiatric Index 12

  baseline and week 30 (end of study)

Other Outcomes (16)

• Resource Utilization in Dementia (short version, Lite)

  baseline and week 30 (end of study)

• volumetric magnetic resonance imaging (vMRI)

  baseline and week 30 (end of study)

• cortical metabolic rate using fluorodeoxyglucose positron emission

  baseline and week 30 (end of study)

Study Arms (2)

NE3107

EXPERIMENTAL

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

Drug: NE3107

placebo

PLACEBO COMPARATOR

Hard gelatin capsule containing only common excipients for oral formulations

Drug: Placebo

Interventions

NE3107 DRUG

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.

NE3107

Placebo DRUG

capsules that do not contain NE3107

placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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:
• Meets the National Institute on Aging and Alzheimer's Association (NIA-AA, 2011) criteria of all cause dementia and probable AD.
• Has a Clinical Dementia Rating (CDR) (Section 8.1.6) Standard Global Score of 1 to 2, inclusive (mild to moderate).
• 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)
• 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.
• \. Historical evidence of impairment on a mental status exam or documented prior diagnosis of or treatment for dementia from a health care professional.
• \. Has a modified Hachinski Ischemic Scale (Section 8.1.8) score of ≤4 at Screening (V1).
• \. If taking an anticholinesterase inhibitor (AChEI) (e.g., donepezil, galantamine, rivastigmine) and/or memantine at Screening (V1):
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• Must have been taking the medication(s) for ≥3 mo, and
• 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.
• \. 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.
• \. 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.

You may not qualify if:

• \. 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.
• Should there be any evidence of neurologic symptoms between the date of the scan confirming diagnosis and Screening (V1), rescanning is necessary.
• \. Has clinically relevant abnormal laboratory tests including serum vitamin B12 deficiency, thyroid function abnormality, severe anemia, or electrolyte abnormality.
• \. 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.
• \. History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within 12 mo prior to Screening (V1).
• \. 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.
• \. Has any of the following laboratory findings at Screening (V1):
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• 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.
• Hemoglobin ≤10 g/dL.
• 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).
• Creatinine clearance (Cockcroft Gault formula) of \<45 mL/min.
• 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.
• \. Female subjects with child-bearing potential (premenopausal, menstrual bleeding within the last 12 months) or who are pregnant or breastfeeding.
• \. 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.

Sponsors & Collaborators

• BioVie Inc.: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Related Publications (2)

• Reading CL, Ahlem CN, Murphy MF. NM101 Phase III study of NE3107 in Alzheimer's disease: rationale, design and therapeutic modulation of neuroinflammation and insulin resistance. Neurodegener Dis Manag. 2021 Aug;11(4):289-298. doi: 10.2217/nmt-2021-0022. Epub 2021 Jul 12.

  PMID: 34251287 BACKGROUND

• Reading CL, Yan J, Testa MA, Simonson DC, Javaid H, Schmunk L, Martin-Herranz DE, Brooke R, Gordevicius J, Zhang J, Yuan H, Ahlem C, Wang L, Markham P, Osman N, O'Quinn S, Palumbo J. An exploratory analysis of bezisterim treatment associated with decreased biological age acceleration, and improved clinical measure and biomarker changes in mild-to-moderate probable Alzheimer's disease. Front Neurosci. 2025 May 2;19:1516746. doi: 10.3389/fnins.2025.1516746. eCollection 2025.

  PMID: 40386807 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 16, 2020
• Study Start: August 5, 2021
• Primary Completion: September 30, 2023
• Study Completion: October 25, 2023
• Last Updated: November 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)