Huntington Huntington Chorea
Conditions
Interventions
Pridopidine 45 mg BID or placebo BID
Sponsors
Prilenea Neurotherapeutics Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Main study: 1. Twenty-five years of age (inclusive) and older, at the time of signing the informed consent. 2. Diagnosis of HD based on clinical features and the presence of >=36 CAG repeats in the HTT, confirmed by historical laboratory quantified results or by a diagnostic test at screening. 3. Diagnostic confidence level (DCL) of 4 (unequivocal motor signs, >= 99% confidence) on the standardized motor exam UHDRS-TMS. 4. Adult-onset HD with onset of signs and symptoms >=18 years of age. 5. Stage 1 or Stage 2 HD, defined as a UHDRS-TFC score of >=7, at screening. 6. UHDRS-Independence scale (IS) score =20 at the Screening visit. 8. Must meet all criteria required to move forward with the Randomization Authorization Flow (RAF) and be considered eligible by the RAF Reviewer. 9. Male or female. 10. Female participants of childbearing potential must have a negative β-human chorionic gonadotropin (β-HCG) test at screening and baseline, be sterile, or be postmenopausal. 11. Female participants of childbearing potential whose male partners are potentially fertile (i.e., no vasectomy) must use highly effective birth control methods stable for at least 3 months prior to screening, for the duration of the study and for 30 days after discontinuation of the study drug. 12. Male participants must be sterile, or if they are potentially fertile/reproductively competent (not surgically [e.g., vasectomy] or congenitally sterile) and their female partners are of childbearing potential, they must use, together with their female partners, effective birth control methods for the duration of the study and for 90 days after study drug discontinuation. 13. For participants taking allowed antipsychotic, antidepressant, or other psychotropic medication, the dosing of medication as listed in Section 10.6, must be stable for at least 4 weeks before the Baseline visit and throughout the study (unless clinically necessary to change). 14. For participants taking allowed concomitant medications, dosing of medications must be stable for at least 4 weeks prior to the Baseline visit (note: Amiodarone is not allowed within 6 weeks of Baseline Visit) 15. Capable of providing signed informed consent. Inclusion criteria - Open-label Extension 1. Completed the EoS visit of the Main study on treatment without important protocol deviations impacting efficacy and safety assessments. 2. Capable of providing signed informed consent for the OLE. 3. Must meet all criteria required to move forward with the OLE assessments.
Exclusion criteria
Exclusion criteria: Exclusion criteria Main study: 1. Prolonged QTcF interval (defined as a QTcF interval of >450 ms for male and >470 ms for female) at screening. 2. Clinically significant heart disease within 12 weeks before randomization, defined as follows: a. Participants with clinically significant heart disease, a clinically significant history of arrhythmia, symptomatic or uncontrolled atrial fibrillation despite treatment, or confirmed ventricular tachycardia, or presence of left bundle branch block. b. Participants with a known history of congenital long QT syndrome or a first degree relative with this condition. c. Clinically significant bradycardia, sick sinus syndrome, complete atrioventricular block, congestive heart failure, polymorphic ventricular tachycardia, clinically relevant hypocalcemia, hypokalemia or hypomagnesemia. 3. History of epilepsy or seizures within the last 5 years. 4. Serious medical illness (includes, but not limited to, uncontrolled hypertension; respiratory disease, including severe forms of asthma; severe hepatic disease (confirmed Hepatitis B virus [HBV], Hepatitis C virus [HCV];, confirmed human immunodeficiency virus [HIV]); renal disease; acquired immune deficiency syndrome; and unstable psychiatric or other neurologic disorders) and metastatic cancer. For serious kidney and and liver liver illnesses see also exclusion criterion 12 (laboratory test abnormalities) 5. Known intracranial neoplasms, vascular malformations, history of cerebrovascular accident, or intracranial hemorrhage. 6. Female participants who are pregnant, planning to become pregnant or breastfeeding 7. Medications that prolong QT interval, taken within 4 weeks of the Baseline visit (note, Amiodarone is not allowed within 6 weeks of the Baseline visit) or at any timepoint during the study, including non-allowed antipsychotic medications, tricyclic antidepressants, and/or Class I antiarrhythmics 8. Use of pridopidine within 12 months before the Baseline visit. 9. Treatment with any investigational product within 6 weeks or 5 half-lives (whichever is longer) before the Screening visit or a plan to participate in another clinical study that assesses any investigational product during the study. 10. Gene therapy at any time 11. Prior particpation in studies with tominersen at any time 12. Laboratory values that fall outside of the central laboratory*s reference range at screening and are considered clinically significantly abnormal by the Investigator, and affect the participant's suitability to participate in the study or put the participant at risk if he/she enters the study in the Investigator*s opinion. 13. Have any of the following laboratory test abnormalities at screening a. CrCl <30 mL/min at screening, calculated using the CockcroftGault equation: (140-age) × mass (kg) × [0.85 if female] / 72 × serum creatinine (mg/dL). b. Aspartate aminotransferase (AST) >=2.5 × upper limit of normal (ULN) c. Alanine aminotransferase (ALT) >=2.5 × ULN d. Gamma- glutamyl transferase (GGT) >=3.0 × ULN e. Total bilirubin >1,5 mg/dL, except participants with unconjugated hyperbilirubinemia without other liver function derangements or other explanations for the elevated bilirubin (consistent with diagnosis of Gilbert*ssyndrome) 14. Alcohol and/or substance use
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective Main study: To assess the effect of pridopidine on functional capacity in participants with stage 1-2 HD Primary endpoint Main Study: Change from baseline to Week*65 in the UHDRS-TFC score. Primary objective Main study and OLE: To evaluate the long-term treatment effect of pridopidine in participants with HD who previously completed the Main study Primary endpoint OLE: Change in -UHDRS-TFC -UHDRS-TMS - Quantitative motor (Q-Motor): o finger tapping (Digitomotography) o pronation/supination (Dysdiadochomotography) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secundary objectives Main Study: Multiplicity Adjusted Secondary Endpoints: Key Secondary (secondary endpoints are listed by order of hierarchy) 1. To assess the effect of pridopidine on a composite measure of disease progression in participants with HD Secondary (secondary endpoints are listed by order of hierarchy) 2. To evaluate the effect of pridopidine on functional capacity, motor function, and other measures of efficacy over time in participants with HD Non-multiplicity Adjusted Secondary Endpoints: 3. To evaluate the effects of pridopidine in participants with HD Safety and Tolerability 4. To evaluate the safety and tolerability of pridopidine in participants with HD Exploratory To evaluate the exploratory efficacy effects of pridopidine in participants with HD Biomarker To evaluate changes in disease biomarker plasma neurofilament light chain (NfL) following treatment with pridopidine in participants with HD PK To evaluate the pharmacokinetics (PK) of pridopidine and its main metabolite in participants with HD Secundary endpoints Main Study: Multiplicity Adjusted Secondary Endpoints: 1: 1. Change from Baseline to Week 65 in composite UHDRS (cUHDRS) total score 2: 2. Proportion of participants with no worsening (change >= 0 point) from baseline to Week 65 in UHDRS-TFC 3. Change from baseline to Week 52 in UHDRS-TFC score 4. Change from baseline to Week 78 in UHDRS-TFC score 5. Change from baseline to Week*65 in Quantitative motor (Q-Motor) finger tapping inter-onset interval (IOI) mean (Digitomotography) 6. Change from baseline to Week*65 in the UHDRS Total Motor Score (TMS) 7. Change from Baseline to Week 65 in Symbol Digit Modalities Test (SDMT) 8. Change from baseline to Week 52 in UHDRS-TMS score 9. Proportion of participants with no worsening from baseline in Clinical Global Impression of Change (CGI-C) at Week 65 Non-multiplicity Adjusted Secondary Endpoints: 3: • Change from Baseline to Week 26 and 39 in the UHD | — |
Countries
Netherlands
Outcome results
None listed