Within Subject Crossover Study of Cognitive Effects of Neflamapimod in Early-Stage Huntington Disease

NCT03980938 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: EIP19-NFD-401
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, placebo-controlled 2-period 10-week treatment within-subject crossover study of neflamapimod in early-stage Huntington disease (HD). The primary objective is to determine whether neflamapimod can reverse hippocampal dysfunction in patients with early-stage HD, as assessed by the virtual water-maze-test for evaluating spatial learning and selected tests on the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (1)

• Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM)

  Change from baseline of latency during the learning phase of vMWM (hidden platform training) in the neflamapimod first group compared to placebo first group

  Baseline and 10 Weeks

Study Arms (2)

neflamapimod first

EXPERIMENTAL

neflamapimod in Treatment Period 1, placebo in Treatment Period 2 neflamapimod: 40 mg neflamapimod hard gelatin capsules, taken twice daily with food. Placebo: hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food.

Drug: neflamapimod; Other: Placebo

placebo first

PLACEBO COMPARATOR

placebo in Treatment Period 1, neflamapimod in Treatment Period 2 Placebo: hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food. neflamapimod: 40 mg neflamapimod hard gelatin capsules, taken twice daily with food.

Drug: neflamapimod; Other: Placebo

Interventions

neflamapimod DRUG

40 mg neflamapimod capsule

Also known as: VX-745

neflamapimod first; placebo first

Placebo OTHER

matching placebo capsule

neflamapimod first; placebo first

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women age 30 to 70 years, inclusive.
• Willing and able to provide informed consent.
• Must have genetically confirmed HD and identified cognitive deficits:
• Stage 1, as defined by Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score \>10, and,
• CANTAB Paired Associate Learning Total Adjusted Error Score of \>16.
• Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
• No history of learning difficulties that may interfere with the subject's ability to complete the cognitive tests.

You may not qualify if:

• A profile of impairment that is not consistent with HD.
• Diagnosis of any other ongoing central nervous system condition other than HD, including, but not limited to, vascular dementia, dementia with Lewy bodies, and Parkinson's disease.
• Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
• Ongoing major and active psychiatric disorder, moderate to severe depressive symptoms, and or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
• Diagnosis of alcohol or drug abuse within the previous 2 years.
• Poorly controlled clinically significant medical illness, such as hypertension (blood pressure \>180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would preclude treatment with p38 mitogen activated protein (MAP) kinase inhibitor and/or assessment of drug safety and efficacy.
• Anemia with a hemoglobin ≤10 g/dL, clinically significant thyroid function abnormality, electrolyte abnormalities.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 × the upper limit of normal (ULN), total bilirubin \>1.5 × ULN, and/or International Normalized Ratio (INR) \>1.5.
• Known human immunodeficiency virus; or active hepatitis B or hepatitis C virus infection; evidence of active or latent tuberculosis.
• Subject participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
• History of previous neurosurgery to the brain.
• Female subjects who are pregnant or breast-feeding.
• Male subjects with female partners of child-bearing potential who are unwilling or unable to adhere to contraception requirements specified in the protocol (see Section 5.8).
• Female subjects who have not reached menopause or have not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy and are not willing or unable to adhere to contraceptive requirements specified in the protocol (see Section 5.8).
• Requires concomitant use of cytochrome P450 (CYP) 3A4 inhibitors or anti-tumor necrosis factor-alpha therapies during study participation.

Sponsors & Collaborators

• EIP Pharma Inc: lead
• Voisin Consulting, Inc.: collaborator

Study Sites (1)

John Van Geest Centre for Brain Repair

Cambridge, CB2 0PY, United Kingdom

Location

Related Publications (1)

• Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.

  PMID: 33974419 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

VX-745

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

Due COVID-19 pandemic all clinical research in the UK was halted in March 2020. Sponsor ultimately elected to terminate the study on 15 October 2020. As only one subject completed both periods of the crossover, the only efficacy analyses compared outcomes in subjects receiving neflamapimod (N=7) during Treatment period 1 to those receiving placebo during that period (N=8); i.e., an inter-subject group comparison, rather than the within-subject comparison for which the study was powered.

Results Point of Contact

• Title: Jennifer Conway
• Organization: EIP Pharma, Inc

jconway@eippharma.com

(617) 744-4400

Study Officials

• John Alam, MD

  EIP Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: June 10, 2019
• Study Start: July 8, 2019
• Primary Completion: October 15, 2020
• Study Completion: October 15, 2020
• Last Updated: April 6, 2022
• Results First Posted: April 6, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)