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Alzheimer DiseasePhase 3NCT04669028

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

A Phase 3 study testing NE3107 in people with Alzheimer Disease, run by BioVie Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 60 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
NE3107
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
439 participants
Where
1 siteUnited States
Study dates
5 Aug 2021to 25 Oct 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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.
  • 3. Historical evidence of impairment on a mental status exam or documented prior diagnosis of or treatment for dementia from a health care professional.
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  • 4. Has a modified Hachinski Ischemic Scale (Section 8.1.8) score of ≤4 at Screening (V1).
  • 5. If taking an anticholinesterase inhibitor (AChEI) (e.g., donepezil, galantamine, rivastigmine) and/or memantine at Screening (V1):
  • <!-- -->
  • 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.
  • 6. 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.
  • 7. 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.
  • 8. Must meet one of the following criteria:
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  • 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
  • Males: Vasectomized. If not vasectomized, must use an appropriate contraception method as noted in Section 6.8.1.
  • 9. 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.
  • 10. Willing to allow collection of blood for ApoE genotyping. 11. Able to comply with the study procedures, in the opinion of the Investigator.
  • 12. 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.

Who cannot join

  • 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.
  • Should there be any evidence of neurologic symptoms between the date of the scan confirming diagnosis and Screening (V1), rescanning is necessary.
  • 3. Has clinically relevant abnormal laboratory tests including serum vitamin B12 deficiency, thyroid function abnormality, severe anemia, or electrolyte abnormality.
  • 4. 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.
  • 5. History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within 12 mo prior to Screening (V1).
  • 6. 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.
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  • 7. 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.
  • 8. Female subjects with child-bearing potential (premenopausal, menstrual bleeding within the last 12 months) or who are pregnant or breastfeeding.
  • 9. 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.
  • 10. 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.
  • 12. 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.
  • 13. 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.
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  • 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).
  • 14. Violent or aggressive behavior that may interfere with study participation 15. 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.
  • 16. 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.
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  • Positive urine screen for drugs of abuse that include methadone, cocaine, and amphetamines; positive urine screen for opiates, barbiturates, or benzodiazepines without a prescription.
  • 17. 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.
  • 18. 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Ohio State University

    Columbus, Ohio, 43221

Other trials in United States

About this study

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

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.

Being tested
NE3107, Placebo
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NE3107Drug

    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.

  • PlaceboDrug

    capsules that do not contain NE3107

Study groups in NCT04669028
Study groupRoleWhat they receive
NE3107ExperimentalHard gelatin capsule containing 20 mg micronized NE3107 drug substance blended with common excipients for oral formulations
Receives: Drug: NE3107
placeboPlacebo comparatorHard gelatin capsule containing only common excipients for oral formulations
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: baseline and week 30 (end of study)

  2. 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.

    Measured: baseline and week 30 (end of study)

Secondary outcomes (6)

  1. Alzheimer's Disease clinical COMposite Score (ADCOMS)

    composite score of questions from different cognitive tests (CDR, MMSE, and ADAS-Cog12). total score ranges from 0-1.97, with higher scores indicating worse disease

    Measured: baseline and week 30 (end of study)

  2. Alzheimer's Disease Cooperative Study Activities of Daily Living Scale

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

    Measured: baseline and week 30 (end of study)

  3. Mini Mental State Exam (MMSE)

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

    Measured: baseline and week 30 (end of study)

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

    The ADCS-CGIC focuses on clinicians' observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. It relies on both direct examination of the subject and interview of informants (e.g. trial partner). global severity at baseline scored from 1 (normal, not at all ill) to 7 (among the most extremely ill patients); and global change at follow-up scored from 1 (marked improvement) to 7 (marked worsening), where 4 indicates no change.

    Measured: baseline and week 30 (end of study)

  5. Neuropsychiatric Index 12

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

    Measured: baseline and week 30 (end of study)

  6. CDR Global Score

    The CDR is a 5-point scale used to characterize 6 domains of cognitive and functional performance applicable to AD and related dementias. Higher score is more severe disease symptoms. The overall CDR Global Score is calculated through the use of an algorithm. 0= normal, 0.5= very mild dementia, 1=mild dementia, 2=moderate dementia, 3=severe dementia

    Measured: baseline and week 30 (end of study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2020
  2. Study start5 Aug 2021
  3. Primary completion30 Sep 2023
  4. Study completion25 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
439 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04669028
Sponsor's protocol ID
NM101
Status last verified
Nov 2023
First submitted
4 Dec 2020
Last updated
21 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34251287

  • 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.

    PubMed 40386807

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NE3107 in people with Alzheimer Disease, run by BioVie Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) (time frame: baseline and week 30 (end of study)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04669028, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2023.

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