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

Official 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.

Eligibility Requirements

• Minimum Age: 60 Years
• Maximum Age: 85 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 439 participants

Study Arms

• NE3107 (EXPERIMENTAL)
  Hard gelatin capsule containing 20 mg micronized NE3107 drug substance blended with common excipients for oral formulations
• placebo (PLACEBO_COMPARATOR)
  Hard gelatin capsule containing only common excipients for oral formulations

Interventions

• 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.
• DRUG: Placebo — capsules that do not contain NE3107

Primary Outcomes

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) (baseline and week 30 (end of study))
• Change in Alzheimer's Disease Assessment Scale Cognitive Subscale 12 [ADAS Cog12] (baseline and week 30 (end of study))

Secondary Outcomes

• 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))

Eligibility Criteria

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.

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

     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):

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  1. Must have been taking the medication(s) for ≥3 mo, and
  2. 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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  1. 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
  2. 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.

     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.

     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.

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

 

Trial Locations

• The Ohio State University, Columbus, Ohio, United States

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