A Phase 2, to Evaluating the Safety and Efficacy of Pridopidine Vs Placebo for Symptomatic Treatment in Patients With Huntington's Disease

A Phase 2, Dose-Finding, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study, Evaluating the Safety and Efficacy of Pridopidine 45, 67.5, 90, and 112.5 mg Twice-Daily vs Placebo for Symptomatic Treatment in Patients With Huntington's Disease

This is a multicenter, multinational, randomized, parallel-group, double-blind, placebo-controlled, dose range finding study to compare the efficacy and safety of different doses of pridopidine versus placebo in the treatment of motor impairment in Huntington's Disease (HD).

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: Pridopidine; Other: Placebo

Detailed Description

Originally, the study was designed to assess the effect of pridopidine on motor function at 26 weeks. Due to the recognition that the primary target of pridopidine is the Sigma-1 receptor, the trial was extended from 26 to 52 weeks to evaluate the effect of pridopidine on Total Functional Capacity (TFC). A minimum of 52 weeks are needed for the placebo group to decline and allow a window to assess an effect on TFC (a prespecified endpoint). Approximately 20% of patients completed 26 weeks of the study before IRB approvals for this extension, and did not continue into the 2nd treatment period up to 52 weeks.

• Study Type: Interventional
• Enrollment (Actual): 408
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Caulfield South, Australia
    • Investigational Site 78055
  • Kew, Australia
    • Investigational Site 78056
  • Subiaco, Australia
    • Investigational Site 78058
  • Westmead, Australia
    • Investigational Site 78057
• Austria
  • Innsbruck, Austria
    • Investigational Site 33021
  • Wien, Austria
    • Investigational Site 33027
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Investigational Site 11035
  • Ontario
    • Ottawa, Ontario, Canada
      • Investigational Site 11037
    • Toronto, Ontario, Canada
      • Investigational Site 11036
• Denmark
  • Aarhus, Denmark
    • Investigational Site 39028
  • Copenhagen, Denmark
    • Investigational Site 39027
• France
  • Angers cedex 9, France
    • Investigational Site 35123
  • Creteil, France
    • Investigational Site 35122
  • Lille, France
    • Investigational Site 35125
  • Marseille Cedex 5, France
    • Investigational Site 35124
  • Salouel, France
    • Investigational Site 35121
  • Toulouse, France
    • Investigational Site 35165
• Germany
  • Berlin, Germany
    • Investigational Site 32408
  • Bochum, Germany
    • Investigational Site 32410
  • Muenster, Germany
    • Investigational Site 32409
  • Ulm, Germany
    • Investigational Site 32407
• Italy
  • Firenze, Italy
    • Investigational Site 30083
  • Milano, Italy
    • Investigational Site 30080
  • Napoli, Italy
    • Investigational Site 30082
  • Pozzilli, Italy
    • Investigational Site 30081
  • San Giovanni Rotondo, Italy
    • Investigational Site 30084
• Netherlands
  • Leiden, Netherlands
    • Investigational Site 38059
• Poland
  • Gdansk, Poland
    • Investigational Site 53150
  • Krakow, Poland
    • Investigational Site 53149
  • Poznan, Poland
    • Investigational Site 53148
  • Warsaw, Poland
    • Investigational Site 53151
• Russian Federation
  • Kazan, Russian Federation
    • Investigational Site 50215
  • Moscow, Russian Federation
    • Investigational Site 50213
  • Nizhny Novgorod, Russian Federation
    • Investigational Site 50214
• United Kingdom
  • Birmingham, United Kingdom
    • Investigational Site 34058
  • Cambridge, United Kingdom
    • Investigational Site 34054
  • Cardiff, United Kingdom
    • Investigational Site 34059
  • Headington, United Kingdom
    • Investigational Site 34056
  • London, United Kingdom
    • Investigational Site 34060
  • Manchester, United Kingdom
    • Investigational Site 34055
  • Newcastle-Upon-Tyne, United Kingdom
    • Investigational Site 34061
  • Sheffield, United Kingdom
    • Investigational Site 34057
• United States
  • California
    • La Jolla, California, United States
      • Investigational Site 12199
    • Los Angeles, California, United States
      • Investigational Site 12204
  • Colorado
    • Englewood, Colorado, United States
      • Investigational Site 12201
  • District of Columbia
    • Washington, District of Columbia, United States
      • Investigational Site 12196
  • Illinois
    • Chicago, Illinois, United States
      • Investigational Site 12207
  • Maryland
    • Baltimore, Maryland, United States
      • Investigational Site 12202
    • Baltimore, Maryland, United States
      • Investigational Site 12206
  • New York
    • Manhasset, New York, United States
      • Investigational Site 12200
    • New York, New York, United States
      • Investigational Site 12203
    • Rochester, New York, United States
      • Investigational Site 12198
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • Investigational Site 12211
  • Ohio
    • Cincinnati, Ohio, United States
      • Investigational Site 12205
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Investigational Site 12209
  • Utah
    • Salt Lake City, Utah, United States
      • Investigational Site 12208
  • Virginia
    • Richmond, Virginia, United States
      • Investigational Site 12210
  • Washington
    • Kirkland, Washington, United States
      • Investigational Site 12197

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of HD based on the presence of >/= 36 CAG repeats
• Male or female age ≥21 years, with an onset of HD after 18 years' old.
• Females of childbearing potential must be compliant in using adequate birth control throughout the duration of the study
• Body weight ≥50 kg
• Sum of >= 25 points on the UHDRS-TMS and UHDRS Independence Score <=90%
• Able and willing to provide written informed consent prior to any study related procedure.
• Willing to provide a blood sample for genetic analyses
• Willing and able to take oral medication and able to comply with the study specific procedures.
• Ambulatory, being able to travel to the study center, and judged by the investigator as likely to be able to continue to travel for the duration of the study.

• Availability and willingness of a caregiver, informant or family member to accompany the patient to the clinic at study, and the suitability of the caregiver should be judged by the Investigator.

  • Other criteria apply, please contact the investigator for more information.

Exclusion Criteria:

• Patients with clinically significant heart disease at the screening visit
• Treatment with tetrabenazine within 6 weeks of study screening
• Patients with a history of epilepsy or of seizures within the last 5 years
• Have other serious medical illnesses in the opinion of the investigator may put the patient at risk when participating in the study or may influence the results of the study or affect the patient's ability to take part in the study

• Patients receiving medications (within the last 6 weeks prior to screening) that have been proven to prolong QT interval or who may require such medications during the course of the study such as but not limited to non allowed anti psychotic medications, tricyclic antidepressants and/or Class I antiarrhythmics

  • Other criteria apply, please contact the investigator for more information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Twice daily	Other: Placebo; Capsules matching drug
Experimental: Pridopidine 45 mg; Twice daily	Drug: Pridopidine; 22.5 mg and 45 mg capsules; Other Names: TV7820; Other: Placebo; Capsules matching drug
Experimental: Pridopidine 67.5 mg; Twice daily	Drug: Pridopidine; 22.5 mg and 45 mg capsules; Other Names: TV7820; Other: Placebo; Capsules matching drug
Experimental: Pridopidine 90 mg; Twice daily	Drug: Pridopidine; 22.5 mg and 45 mg capsules; Other Names: TV7820; Other: Placebo; Capsules matching drug
Experimental: Pridopidine 112.5 mg; Twice daily	Drug: Pridopidine; 22.5 mg and 45 mg capsules; Other Names: TV7820; Other: Placebo; Capsules matching drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS) at Week 26	TMS was defined as the sum of all UHDRS motor domains ratings. The motor section of the UHDRS assesses motor features of Huntington's Disease (HD) with standardized ratings of oculo-motor function, dysarthria, chorea, dystonia, gait, and postural stability. Each of 15 assessments is rated on a scale of 0 (normal) to 4 (marked impairment) for a TMS range of 0-124. Negative change from baseline values indicate improvement.	26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Adverse Events	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Functional Capacity (TFC) at Week 52	The TFC is one subscale of the Unified Huntington's Disease Rating Scale (UHDRS), comprising 5 functional domains associated with disability (occupation, finances, domestic chores, activities of daily living, and care level), with scores on each item ranging from 0 to either 2 or 3. The TFC total score is the sum of the 5 TFC items and can range from 0 to 13, with greater scores indicating higher functioning. Negative change from baseline indicates worsening.	52 weeks

Collaborators and Investigators

• Sponsor: Prilenia
• Collaborators: Huntington Study Group; European Huntington's Disease Network

Publications and helpful links

General Publications

• Rodrigues FB, Quinn L, Wild EJ. Huntington's Disease Clinical Trials Corner: January 2019. J Huntingtons Dis. 2019;8(1):115-125. doi: 10.3233/JHD-190001.
• McGarry A, Leinonen M, Kieburtz K, Geva M, Olanow CW, Hayden M. Effects of Pridopidine on Functional Capacity in Early-Stage Participants from the PRIDE-HD Study. J Huntingtons Dis. 2020;9(4):371-380. doi: 10.3233/JHD-200440.
• Reilmann R, McGarry A, Grachev ID, Savola JM, Borowsky B, Eyal E, Gross N, Langbehn D, Schubert R, Wickenberg AT, Papapetropoulos S, Hayden M, Squitieri F, Kieburtz K, Landwehrmeyer GB; European Huntington's Disease Network; Huntington Study Group investigators. Safety and efficacy of pridopidine in patients with Huntington's disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study. Lancet Neurol. 2019 Feb;18(2):165-176. doi: 10.1016/S1474-4422(18)30391-0. Epub 2018 Dec 15.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2014
• Primary Completion (Actual): December 16, 2015
• Study Completion (Actual): July 7, 2016

Study Registration Dates

• First Submitted: December 5, 2013
• First Submitted That Met QC Criteria: December 5, 2013
• First Posted (Estimate): December 10, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Huntington's Disease; Pridopidine; Pride-HD
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: TV7820-CNS-20002; 2013-001888-23 (EudraCT Number)