A study to assess the safety and efficacy of a new medicine SBT-020 in patients with Early Stage Huntington’s Disease.

• Register: EUCTR
• Last refreshed on: 12 February 2018
• Main ID: EUCTR2016-003730-25-NL
• Date of registration: 09/01/2017
• Prospective Registration: Yes
• Primary sponsor: Stealth Bio Therapeutics Inc
• Public title: A study to assess the safety and efficacy of a new medicine SBT-020 in patients with Early Stage Huntington’s Disease.
• Scientific title: A Two Part Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of SBT-020 in Patients with Early Stage Huntington’s Disease. - SBT-020 in HD
• Date of first enrolment: 14/02/2017
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003730-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Principal Investigator
• Affiliation: Centre for Human Drug Research

• Name: Principal Investigator
• Affiliation: Centre for Human Drug Research

Key inclusion & exclusion 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:
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 < 60 mL/min (calculated by the Modification of Diet in Renal Disease equation) at Screening.
7. Clinically significant abnormalities, as judged by the Investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for HD patients.
8. Participation in an investigational drug or device study within 3 months prior to screening.
9. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.
10. Concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
11. Presence of any contraindication to have MRI scans performed (e.g. claustrophobia, pacemaker, vascular clips etc.). MRI contraindications for both the 7 Tesla (part 1 and 2) and 3 T (part 2 only) MRIs will be assessed, using MRI contra-indications questionnaires and, if necessary, a plain radiograph
12. Unwillingness to refrain from smoking more than half pack cigarettes per day (i.e. 10 units).
13. Specific cardiac abnormalities on the resting ECG at screening: QTcF> 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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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

Intervention(s)

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 descriptive name: SS-20
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-25
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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 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 (Part 2 only)
- Intensity of red-green fluorescence, measured by flow-cytometry in PBMCs
Various exploratory plasma and urinary biomarkers for mitochondrial function
Neuropsychological function (Part 2 only)
- NeuroCart and paper and pencil assessments
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 (Part 2 only)
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 (degrees/second), saccadic inaccuracy (%) on the Saccadic eye movements test
o percentage of time the eyes are in smooth pursuit of the target (%) on the Smooth pursuit test
o antero-posterior sway (in mm) on the Bodysway test

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

Timepoint(s) of evaluation of this end point: Day 1 - Day 42

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

SBT20-102

Source(s) of Monetary Support

Stealth Biotherapeutics