Randomized, Placebo Controlled Study Of The Efficacy And Safety Of PF-02545920 In Subjects With Huntington's Disease

Huntington's Disease Clinical Trial

Official title:

A Phase 2, Randomized, Placebo Controlled, Double Blind Proof-of-concept Study Of The Efficacy And Safety Of Pf-02545920 In Subjects With Huntington's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02197130
• Other study ID #: A8241021
• Secondary ID: 2014-001291-56
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2014
• Last updated: October 13, 2017
• Start date: September 2014
• Est. completion date: October 2016

Study information

• Verified date: October 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a 26 week, randomized, parallel group, double blind comparison of PF-02545920 5 mg, PF-02545920 20 mg, and placebo dosed BID in the treatment of motor impairment of subjects with Huntington's Disease. A total of approximately 260 subjects are planned to be randomized in the study. Primary endpoint is the change from baseline in the Total Motor Score (TMS) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 26 weeks of treatment. secondary endpoints will include change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS after 13 and 26 weeks of treatment and Clinical Global Impression-Improvement score after 13 and 26 weeks of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: October 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

• CAG repeat equal or greater than 36;

• Total motor score equal or greater than 10;

• Total functional capacity equal or greater than 7.

Exclusion Criteria:

• Clinically significant neurologic disorder other than Huntington's disease;

• Other severe acute psychiatric conditions, mania and/or psychosis;

• History of neutropenia, and myeloproliferative disorders;

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• PF-02545920
20 mg twice a day (BID) for 26 weeks. Each 20 mg dose will be taken as 4 tablets of 5 mg. The 20mg dose will be titrated as follow: 5mg BID for 7 days, 10mg BID for 7 days, 15 mg BID for 7 days and 20 mg BID to week 26. Study drug will be provided in weekly blister cards.
• PF-02545920
5 mg twice a day (BID) for 26 weeks. Each 5 mg dose will be taken as 4 tablets: one tablet of 5 mg and 3 tablets of matching placebo. The 5mg dose will not be titrated. Study drug will be provided in weekly blister cards.

Other:
• Placebo
Matching Placebo twice a day (BID) for 26 weeks. Each placebo dose will be taken as 4 tablets of matching Placebo. The placebo dose will not be titrated. Matching placebo will be provided in weekly blister cards.

Locations

Country	Name	City	State
Canada	CHUM Notre Dame, Pharmacie	Montreal	Quebec
Canada	CHUM-Notre-Dame Hospital	Montreal	Quebec
Canada	Centre for Movement Disorders	Toronto	Ontario
Canada	The Centre for Huntington Disease	Vancouver	British Columbia
Germany	Uniklinik RWTH Aachen	Aachen
Germany	Charite - Universitatsmedizin Berlin	Berlin
Germany	Prof. Dr. Carsten Saft	Bochum
Germany	Friedrich-Alexander-Universität	Erlangen
Germany	Prof. Dr. med. Stephan Klebe	Freiburg
Germany	Universitat zu Lubeck	Lubeck
Germany	Philipps Universitat Marburg	Marburg
Germany	Technische Universität München	Munchen	Bavaria
Germany	George Huntington Institut	Münster
Germany	Kbo-Isar-Amper-Klinikum gGmbH	Taufkirchen
Germany	Universitätsklinikum Ulm	Ulm
Germany	Universitatsklinikum Wuerzburg	Wuerzburg
Poland	Copernicus Podmiot Leczniczy sp. z o.o.	Gdansk
Poland	Krakowska Akademia Neurologii Sp. z o.o.	Krakow
Poland	Solumed Centrum Medyczne	Poznan
Poland	Instytut Psychiatrii i Neurologii	Warszawa
United Kingdom	NHS Grampian, Clinical Genetics Centre	Aberdeen	Aberdeenshire
United Kingdom	Birmingham & Solihull Mental Health NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	John Van Geest Centre for Brain Repair	Cambridge
United Kingdom	University of Wales Hospital	Cardiff
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	Clinical Research Facility	London
United Kingdom	University College London Hospitals Huntington's Disease Research Centre	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust	Manchester
United Kingdom	The National Institute for Health Research/Wellcome Trust Clinical Research Facility	Manchester
United Kingdom	Newcastle Magnetic Resonance Centre	Newcastle Upon Tyne
United Kingdom	St Nicholas Hospital	Newcastle Upon Tyne
United Kingdom	Oxford University Hospitals NHS Trust	Oxford	Oxfordshire
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	South Yorkshire
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire
United States	Albany Medical College	Albany	New York
United States	The Kirklin Clinic of UAB Hospital	Birmingham	Alabama
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	Cleveland Clinic Foundation Hospital Pharmacy	Cleveland	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Davis Medical Center	Columbus	Ohio
United States	The Wexner Medical Center at the Ohio State University	Columbus	Ohio
United States	Wexner Medical Center at the Ohio State University	Columbus	Ohio
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	University of Florida Center for Movement Disorders and Neurorestoration	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Health Neuroscience Center	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	Ronald Regan UCLA Medical Center Drug Information Center	Los Angeles	California
United States	UCLA Neurology Clinic	Los Angeles	California
United States	UCLA Radiology	Los Angeles	California
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Wake Forest Baptist Medical Center - Dept. of Neurology	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment.	The UHDRS was a clinical rating scale which has been developed by the Huntington Disease Study Group (HSG) to provide a uniform assessment of the clinical features and course of Huntington's Disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. The total motor score (TMS) assessed motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. Some items (such as chorea and dystonia) required grading each extremity (face, bucco-oral-lingual, and trunk) separately. Eye movements require both horizontal and vertical grades. The total motor impairment scores was the sum of all the individual 31 motor sub-items (each rated from 0 to 4), with higher scores indicating more severe motor impairment than lower scores. The range of TMS is 0-124.	Baseline, Week 26
Secondary	Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria	The criteria for temporary study suspension was as follow: Criterion A: WBC count <=3000 cells/mm3 but >= 2000 cells/mm3 or ANC <= 1500 cells/mm3 but >= 1000 cells/mm3; Criterion B: WBC <= 2000 cells/mm3 or ANC <= 1000 cells/mm3; Criterion C: participants who are discontinued or permanently suspended due to WBC or ANC findings; Criterion D: ANC <= 500 cells/mm3	Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Number of Participants With Adverse Events	Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Number of Participants With Serious Adverse Events	Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly.	Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormalities)	Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes);coagulation (PT international ratio); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma GT, LDH, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (calcium, sodium, potassium, chloride, total bicarbonate, magnesium, phosphate); clinical chemistry (glucose, glycosylated, hemoglobin, human chorionic gonadotropin, creatine kinase); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity [pH], urine specific gravity, glucose, protein, blood, ketones, nitrite).	Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Number of Participants With Laboratory Test Abnormalities (With Normal Baseline)	Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes);coagulation (PT international ratio); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma GT, LDH, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (calcium, sodium, potassium, chloride, total bicarbonate, magnesium, phosphate); clinical chemistry (glucose, glycosylated, hemoglobin, human chorionic gonadotropin, creatine kinase); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity [pH], urine specific gravity, glucose, protein, blood, ketones, nitrite).	Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values)	Absolute values were analyzed for supine systolic blood pressure (SBP), standing SBP, supine diastolic blood pressure (DBP), standing DBP, supine pulse rate, and standing pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: supine SBP less than (<) 90 millimeter of mercury(mmHg); Criterion B: standing SBP < 90 mmHg; Criterion C: supine DBP <50 mmHg; Criterion D: standing DBP <50 mmHg; Criterion E: supine pulse rate < 40 beats per minute(BPM); Criterion F: supine pulse rate greater than (>)120 BPM; Criterion G: standing pulse rate < 40 beats per minute(BPM); Criterion H: standing pulse rate >120 BPM;	Screening, Day 1, 28, 91, and 182
Secondary	Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline)	The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine SBP greater than or equal to (>=) 30 mmHg; Criterion B: maximum increase from baseline in standing SBP >= 30 mmHg; Criterion C: maximum increase from baseline in supine DBP >=20 mmHg; Criterion D: maximum increase from baseline in standing DBP >=20 mmHg	Screening, Day 1, 28, 91, and 182
Secondary	Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline)	The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine SBP >= 30 mmHg; Criterion B: maximum decrease from baseline in standing SBP >= 30 mmHg; Criterion C: maximum decrease from baseline in supine DBP >=20 mmHg; Criterion D: maximum decrease from baseline in standing DBP >=20 mmHg	Screening, Day 1, 28, 91, and 182
Secondary	Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values)	The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) >=140 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-<480 msec; Criterion D: maximum QTcF interval 480-<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) >=500 msec	Screening, Day 1, 28, 91, and 182
Secondary	Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline)	Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg >=50%; Criterion C: maximum QTcF interval (Fridericia's correction) increase from baseline 30<=change<60 msec; Criterion D: maximum QTcF interval (Fridericia's correction) increase from baseline change >=60 msec.	Screening, Day 1, 28, 91, and 182
Secondary	Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia	Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event). EPS were reported AEs of dystonia and akathisia.	Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment.	The UHDRS was a clinical rating scale which has been developed by the Huntington Disease Study Group (HSG) to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. The Total Maximum Chorea (TMC) was a subset of the TMS assessment. It was composed of the scoring of 7 chorea assessments (face, orobuccolingual, trunk, right and left upper extremities, right and left lower extremities). Each assessment was rated from 0 to 4 (absent to prolonged). TMC is obtained by adding up each of the separate scores, leading to max score of 28. The minimum score is 0. The higher the score, the worse the symptoms. n is the number of evaluable subjects in each visit.	Baseline, Week 13, Week 26
Secondary	Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit	The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. The results presented are the number of participants with completed suicide or non-fatal suicide events or behaviors. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.	Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Secondary	Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment.	CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Clinician responded to a question: "Compared to your subject's condition at the beginning of treatment, how much has your subject changed?". Improvement was compared to baseline and was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. n is the number of evaluable participants in each visit.	Week 13 & Week 26

External Links

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