Within Subject Crossover Study of Cognitive Effects of Neflamapimod in Early-Stage Huntington Disease
Condition: Huntington Disease
MeSH terms: Huntington Disease
Intervention: neflamapimod; Placebo
Intervention description: 40 mg neflamapimod capsule; matching placebo capsule
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 15.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        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.