Huntington's Disease MedDRA version: 20.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: SBT-020
Product Code: SBT-020
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: SBT-020
CAS Number: 1795737-00-6
Current Sponsor code: SBT-020-01
Other de
Sponsors
Stealth Bio Therapeutics Inc
Eligibility
Sex/Gender
All
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. ?PCr 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 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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 < 300 msec, evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker. 14. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable). 15. Unwillingness or inability to comply with the study protocol for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Primary Objective - To assess the safety of SBT-020 in early stage HD patients Part 2: Primary Objective - - To assess the safety and tolerability of longer term treatment with SBT-020 in early stage HD patients. ;Secondary Objective: Part 1 - Effect of SBT-020 on mitochondrial function, measured by 31P-MRS in skeletal muscle. - the pk of SBT-020 in plasma. - The pk of SBT-020 (and SBT-020-related components) in urine - The effect of SBT-020 on mitochondrial function, by measuring MMP in isolated peripheral blood mononuclear cells (PBMCs). Part 2 - Effect of SBT-020 on mitochondrial function, measured by 31P-MRS in skeletal muscle. - The effect of SBT-020 on mitochondrial function, measured by 31P-MRS in the brain. - To assess the plasma concentration of SBT-020 in plasma. - To investigate the effect of SBT-020 on mitochondrial function, by measuring the MMP in PBMCs. - The effect of SBT-020 on an exploratory set of urinary and plasma biomarkers related to mitochondrial function. - Effects of SBT-020 on cognition and other CNS functions, using the NeuroCart test battery. - Effects of SBT-020 on motor functioning, using the NeuroCart test battery and UHDRS ;Primary end point(s): 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. - 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 PK profile. - Urinary SBT-020 (and SBT-020-related components) PK profile. Part 2: - Plasma SBT-020 concentrations. Pharmacodynamic endpoints Mitochondrial function - Mitochondrial function by 31P-MRS o Phosphocreatine recovery time (in sec | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Centre for Human Drug Research
Outcome results
None listed