| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| An hereditary disorder of the central nervous system that affects muscle coordination and leads to cognitive decline and psychiatric problems. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10070668 |
| E.1.2 | Term | Huntington's disease |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate safety and tolerability of pridopidine in patients with HD. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives of the study are to assess the effects of long-term, open-label dosing with pridopidine on motor symptom severity, overall patient function, physical performance, and healthrelated quality of life. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study title: Objective quantification of chorea using a wearable sensor-mobile application tool (Digital Health)
Sub-study Protocol Date: 10 October 2016
Version: included in main Clinical Study Protocol Amendment 02
Objective: To test the hypothesis of using wearable sensor data to estimate clinically relevant measures of HD in patients while on their medication regimen. The aim is to develop algorithms to objectively quantify chorea by analyzing the data from the wearable sensors. |
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| E.3 | Principal inclusion criteria |
a.Patient has completed the PRIDE-HD study (including the follow-up period), or exited from Open PRIDE-HD global or local amendments, all within the last 6 months, or transitioned from Open-HART.
For patients that have failed to complete the PRIDE-HD study or those who exited or completed the above mentioned studies over 6 months prior to the screening visit, and meet all other inclusion criteria, eligibility should be discussed with the Open-PRIDE-HD medical monitor and clinician on a case-by-case basis.
b. For patients that experienced a drug-related serious adverse event during PRIDE-HD, Open-HART, or Open PRIDE-HD global or local amendments, eligibility approval should be discussed with the Open PRIDE-HD medical monitor and clinician. Patients that experienced an adverse event/serious adverse event of active suicidal ideation/behavior will be excluded without discussion.
c. Able and willing to provide written informed consent prior to any study related procedure being performed. Patients with a legal guardian should be consented according to local requirements.
d. Females of child bearing potential have to be compliant in using adequate birth control throughout the duration of the study. Adequate birth control is defined as consistent practice of an effective and accepted method of contraception according to local regulations (hormone-based, intrauterine device, or double barrier contraception, ie, condom and diaphragm). Abstinence is an acceptable method of contraception only when this is the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Male study participants have to be compliant in using adequate birth control with their partners (as defined above) throughout the duration
of the study.
f. Willing and able to take oral medication and able to comply with the study specific procedures.
g. 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.
h. The patient is in good health as determined by medical examination, ECG, serum chemistry, hematology, and urinalysis.
i. The patient must be willing and able to comply with study restrictions and to remain at the investigational center for the required duration during the study period, and willing to return to the investigational center for further visits, as applicable, and the follow up procedures and assessments as specified in this protocol.
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|
| E.4 | Principal exclusion criteria |
a. A prolonged QTcF interval (defined as a QTcF interval of >450 msec) at the screening visit. ECGs will be performed in triplicate during the screening visit, and the mean of the 3 QTcF measurements will be used to determine whether or not the patient is suitable for inclusion in the study.
b. Patients with clinically significant heart disease at the screening visit, defined as follows: (i) significant cardiac event (eg, myocardial infarction), angina pectoris or episode of congestive heart failure with symptoms >Grade 2 New York Heart Association classification within 12 weeks before randomization, or presence of cardiac disease that in the opinion of the investigator increased the risk of ventricular arrhythmia, (ii) history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment (Common Terminology Criteria for Adverse Events Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia, (iii) presence of left bundle branch block.
c. Patients with serum potassium, magnesium, and/or calcium levels outside of the central laboratory’s reference range at the screening visit and considered clinically significantly abnormal by the investigator. Repeat testing is allowed (up to a maximum of 3 tests) if required to establish whether values are within normal range or clinically significantly abnormal.
d. Patients receiving medications (within the last 6 weeks prior to baseline) other than pridopidine 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.
e. Patients receiving medications (within the last 6 weeks prior to baseline) other than pridopidine that are metabolized by CYP2D6 and have the potential of reducing seizure threshold.
f. Patients with a history of epilepsy or of seizures within the last 5 years or the history of seizures currently treated with antiepileptic drugs.
g. Creatinine clearance <60 mL/min at screening, calculated using the Cockcroft-Gault equation: (140 - age) × mass (kg) × [0.85 if female] / 72 × serum creatinine (mg/ dL). It is allowed to repeat the test once, if clinically appropriate.
h. Any clinically significant, abnormal, screening laboratory result which in the opinion of the investigator, affects the patients’ suitability for the study or puts the patient at risk if he/she enters the study.
i.Patients with adverse events of suicidal ideation or attempt at any time in the past or as measured by suicide ideation score of ≥3on the C-SSRS, or PBA-s or patients who answer “Yes” on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) if the attempt or acts were performed at any time in the past, or patients who, in the opinion of the investigator, present a risk of suicide.
j. Females who are pregnant or breastfeeding.
k. Treatment with any investigational product other than pridopidine within 6 weeks of screening or patients planning to participate in another clinical study assessing any investigational product during the study.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The safety endpoints for this study are as follows:
- adverse events
- vital signs assessments
- concomitant medication usage throughout the study
- physical examination findings
- clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis)
- ECG findings
- Suicidality [using the Columbia-Suicide Severity Rating Scale (C-SSRS)] and Problem Behaviors Assessment-Short form (PBA-s)
The tolerability endpoints for this study are as follows:
- Proportion of patients (%) who prematurely discontinued from the study
- Proportion of patients (%) who prematurely discontinued from the study due to AEs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The following safety and tolerability measures will be assessed during the study:
- AEs – monitored at every study visit.
- Vital signs assessments – monitored at every study visit.
- Concomitant medication usage - monitored at every study visit.
- Physical examination findings – brief physical examination will be performed at every study visit.
- Clinical laboratory evaluations (hematology, clin. chemistry, urinalysis) - at each study visit
- ECG findings – ECG will be performed at every study visit
- Suicidality (C-SSRS,PBA-s) will be assessed throughout the study.
Tolerability endpoints:
- Proportion of patients (%) who prematurely discontinued from the study
- Proportion of patients (%) who prematurely discontinued from the study due to AEs |
|
| E.5.2 | Secondary end point(s) |
Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include the following:
- Unified Huntington’s Disease Rating Scale – Total Motor Score (UHDRS-TMS)
- Modified Physical Performance Test (mPPT)
-Unified Huntington’s Disease Rating Scale - Total Functional Capacity (UHDRSTFC)
- Short Form 12 (SF-12) questionnaire (acute version)
- Problem Behaviors Assessment-Short form (PBA-s) (also part of safety assessments)
-Quantitative motor (Q-motor) assessment (up to 104 weeks; not applicable for newly enrolled patients after global Amendment 02) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy analyses will be considered exploratory. Comparisons will generally be made to baseline, as appropriate. Efficacy endpoints include the following:
- UHDRS-TMS - will be performed on site at all visits during the study.
- mPPT - will be performed at baseline, week 12, 26, 52, 78, 104, 130 and visit 26 weeks thereafter
- UHDRS-TFC will be performed at baseline, week 26, 52, 78, 104, 130 and every visit 26 weeks thereafter,
- SF-12 evaluation will be performed at baseline, week 26, 52, 78, 104, 130 and every visit 26 weeks thereafter,
- PBA-s – a full scale will be performed at all on site visits an abbreviated PBA-s will be performed at all safety evaluation TCs
- Q-motor – will be performed at baseline and at weeks 52, 78, and 104. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Austria |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Poland |
| Russian Federation |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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