Early Stage Huntingtons Disease
Conditions
Interventions
SBT-020 or placebo subcutaneously
Huntington's disease
SBT-020
Sponsors
Stealth Bio Therapeutics Inc
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patient with a DNA confirmed diagnosis (CAG expansion of 36 or more repeats in the HTT gene) of HD 2. At least 18 years of age 3. Unified Huntington*s Disease Rating Scale (UHDRS) Total Motor Score (TMS) of 5 or more 4. Unified Huntington*s Disease Rating Scale (UHDRS) Total Functional Capacity Score (TFC) of 7 or more 5. tPCr of at least 32.4 seconds, measured by dynamic 31P-MRS of the calf muscles. 6. Absence of evidence of any significant active or chronic disease (apart from HD), following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis, that might interfere with the study activities or patient*s safety by participating in the study, as judged by the investigator. Psychiatric comorbidities to HD (such as a major depressive disorder), are allowed under the scrutiny of the investigator. 7. Agrees to refrain from making any new, major life-style changes (e.g. starting a new diet or changing their exercise pattern) 8. Must agree to use adequate methods of contraception. Female subjects of childbearing potential must use two adequate forms of contraception, one of which must be a barrier method for the duration of the study and for 30 days after the last dose. Male subjects with a partner of childbearing potential must use two adequate forms of contraception, one of which must be a barrier method, for the duration of the study and for 30 days after the last dose. 9. Able to participate and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Positive test for drugs of abuse, such as metamphetamines and cocaine, at screening or pre-dose, except those prescribed by a physician for treatment of intercurrent medical issues due to HD. 2. History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average. Alcohol consumption will be prohibited during study confinement and at least 24 hours before screening and before each scheduled visit. 3. History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., skin basal or squamous cell carcinoma). 4. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 5. Aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) or total bilirubin levels >1.5 times the upper limit of normal at screening. 6. eGFR 450 or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints - AEs leading to premature discontinuation of study drug. - Treatment-emergent (S)AEs up to 5 pharmacokinetic half-lives after study drug discontinuation. - Change from baseline to End-of-Study in vital signs: blood pressure and heart rate. - Treatment-emergent ECG abnormalities up to 5 pharmacokinetic half-lives after study drug discontinuation. - Treatment-emergent marked laboratory abnormalities up to 5 pharmacokinetic half-lives after study drug discontinuation. Pharmacokinetic endpoints Part 1: - Plasma SBT-020 concentration. Part 2: - Plasma SBT-020 concentration. Pharmacodynamic endpoints - Mitochondrial function by 31P-MRS o Phosphocreatine recovery time (in seconds), measured by 31P-MRS in calf muscles o Difference between Pi/PCr ratio before, during and after visual stimulation, measured by 31P-MRS in the brain - Intensity of red-green fluorescence, measured by flow-cytometry in PBMCs - Various exploratory plasma and urinary biomarkers for mitochondrial function - Neuropsychological assessments (only included in part 2) o total number of correct responses in 90 seconds on the Symbol Digit Modality Test (SDMT) o total number of correct responses in 45 seconds per trial on the Stroop colour word interference test o completion time in seconds and number of errors for each trial on the Trail Making Test (TMT) o total number correct on the Visual Verbal Learning Test (VVLT) o the total number of (commission and omission) errors and the mean reaction time of all correct response trials on the Sustained Attention to Response Task (SART) test o average performance (%) on the Adaptive Tracking task - Motor function (only done during part 2) o total motor score (TMS) (range 0-124) on the UHDRS o total functional capacity score (TFC) score (range 0-13) on the UHDRS o mean tapping rate and standard deviation on the Finger tapping test o saccadic reaction time (seconds), saccadic peak velocity (degr | — |
Countries
The Netherlands
Outcome results
None listed