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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03980938
Recruitment Status : Terminated (Due to the long delay because of COVID-19 and results from another study suggesting a higher dose may be more beneficial, EIP Pharma decided on October 15th, 2020, to end the trial prematurely.)
First Posted : June 10, 2019
Results First Posted : April 6, 2022
Last Update Posted : April 6, 2022
Voisin Consulting, Inc.
Information provided by (Responsible Party):
EIP Pharma Inc

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).

Condition or disease Intervention/treatment Phase
Huntington Disease Drug: neflamapimod Other: Placebo Phase 2

Detailed Description:
The study was designed as within-subject crossover study. However, due to the Covid19 lockdowns and restrictions on clinical research, and only one subject entered the second crossover period. As a result, the baseline and outcomes are reported by the actual treatment received in the subjects during what would have been the first treatment period, i.e. placebo or neflamapimod treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled Two-Period 10-Week Treatment Within-Subject Crossover Study Of Cognitive Effects Of Neflamapimod in Early-Stage Huntington Disease (HD)
Actual Study Start Date : July 8, 2019
Actual Primary Completion Date : October 15, 2020
Actual Study Completion Date : October 15, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: neflamapimod first

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
40 mg neflamapimod capsule
Other Name: VX-745

Other: Placebo
matching placebo capsule

Placebo Comparator: placebo first

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
40 mg neflamapimod capsule
Other Name: VX-745

Other: Placebo
matching placebo capsule

Primary Outcome Measures :
  1. Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM) [ Time Frame: Baseline and 10 Weeks ]
    Change from baseline of latency during the learning phase of vMWM (hidden platform training) in the neflamapimod first group compared to placebo first group

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Men and women age 30 to 70 years, inclusive.
  2. Willing and able to provide informed consent.
  3. Must have genetically confirmed HD and identified cognitive deficits:

    1. Stage 1, as defined by Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score >10, and,
    2. CANTAB Paired Associate Learning Total Adjusted Error Score of >16.
  4. Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
  5. No history of learning difficulties that may interfere with the subject's ability to complete the cognitive tests.

Exclusion Criteria:

  1. A profile of impairment that is not consistent with HD.
  2. 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.
  3. 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.
  4. 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.
  5. Diagnosis of alcohol or drug abuse within the previous 2 years.
  6. 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.
  7. Anemia with a hemoglobin ≤10 g/dL, clinically significant thyroid function abnormality, electrolyte abnormalities.
  8. 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.
  9. Known human immunodeficiency virus; or active hepatitis B or hepatitis C virus infection; evidence of active or latent tuberculosis.
  10. 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.
  11. History of previous neurosurgery to the brain.
  12. Female subjects who are pregnant or breast-feeding.
  13. 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).
  14. 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).
  15. Requires concomitant use of cytochrome P450 (CYP) 3A4 inhibitors or anti-tumor necrosis factor-alpha therapies during study participation.
  16. Known allergy to any ingredient of the trial medication or placebo.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03980938

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United Kingdom
John Van Geest Centre for Brain Repair
Cambridge, United Kingdom, CB2 0PY
Sponsors and Collaborators
EIP Pharma Inc
Voisin Consulting, Inc.
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Study Director: John Alam, MD EIP Pharma
  Study Documents (Full-Text)

Documents provided by EIP Pharma Inc:
Study Protocol  [PDF] July 30, 2019
Statistical Analysis Plan  [PDF] February 3, 2020

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: EIP Pharma Inc Identifier: NCT03980938    
Other Study ID Numbers: EIP19-NFD-401
First Posted: June 10, 2019    Key Record Dates
Results First Posted: April 6, 2022
Last Update Posted: April 6, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders