Huntington Disease
Conditions
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).
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.
Interventions
DRUGneflamapimod
40 mg neflamapimod capsule
OTHERPlacebo
matching placebo capsule
Sponsors
Voisin Consulting, Inc.
EIP Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM) | 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 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Study Terminated | 1 | 1 |
| Treatment Period 2 | Study Terminated | 2 | 2 |
Baseline characteristics
| Characteristic | Neflamapimod First | Placebo First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 7 Participants | 12 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 12.26 | 54.5 years STANDARD_DEVIATION 9.68 | 52.87 years STANDARD_DEVIATION 10.7 |
| Body Mass Index (BMI) | 26.3 kg/m2 STANDARD_DEVIATION 5.4 | 27.61 kg/m2 STANDARD_DEVIATION 6.15 | 27 kg/m2 STANDARD_DEVIATION 5.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 8 Participants | 13 Participants |
| Region of Enrollment United Kingdom | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 4 / 7 | 5 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 |
Outcome results
Primary
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
Time frame: Baseline and 10 Weeks
Population: Participants who had analyzable results at Baseline and Week 10 of Treatment Period 1 (13 participants)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neflamapimod First | Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM) | -6.92 seconds | Standard Deviation 3.814 |
| Placebo First | Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM) | -14.05 seconds | Standard Deviation 12.68 |