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PF-02545920

Phase 2

Huntington's Disease | Small molecule | Rare Disease |Pfizer, Inc.|Last Updated: Dec 14, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials2
Total Enrollment309
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02197130Randomized, Placebo Controlled Study Of The Efficacy And Safety Of PF-02545920 In Subjects With Huntington's DiseasePHASE2 COMPLETED 272Sep 1, 2014Oct 1, 2016Nov 17, 201757 United States, Canada +3
NCT01806896Study Evaluating The Safety, Tolerability And Brain Function Of 2 Doses Of PF-0254920 In Subjects With Early Huntington's DiseasePHASE2 COMPLETED 37Sep 1, 2013Jan 1, 2015Dec 14, 20171 France
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Study Endpoints
Primary Endpoints
Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment.
Baseline, Week 26

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.

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Baseline up to Day 38

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An 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/incapacity; congenital anomaly. Treatment-emergent are events between first dose of treatment and up to the follow-up period that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.

Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern (Without Regard to Baseline Abnormality)
Baseline up to Day 38

The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, platelet count, white blood cell \[WBC\] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen \[BUN\], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total and direct bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy \[if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase\]); others (urine/serum pregnancy test, glycosylated hemoglobin \[HbA1c, if diabetic\]).

Number of Participants With Potentially Clinically Significant Vital Signs Findings
Baseline up to Day 38

Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate less than (\<)40 or greater than (\>)120 beats per minute (bpm), standing pulse rate \<40 or \>140 bpm; systolic blood pressure (SBP) of greater than or equal to (\>=)30 millimeters of mercury (mmHg) change from baseline or SBP \<90 mmHg, diastolic blood pressure (DBP) \>=20 mmHg change from baseline or DBP \<50 mmHg.

Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Baseline up to Day 38

ECG parameters included PR interval, QRS complex, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval ≥200 milliseconds (msec) or ≥25% increase when baseline is \>100 msec; QRS interval ≥50% increase from baseline when baseline is less than or equal to (\<=)200 msec; and QTcF ≥450 msec or ≥30 msec increase from baseline.

Number of Participants With Change From Baseline in Body Weight of >=7%
Baseline up to Day 38

Weight assessment was performed by a study physician or a trained study nurse and was included in the physical examination.

Categorical Summary of Participants Meeting Stopping Criteria
Baseline up to Day 38

Absolute neutrophil count (ANC) and WBC were monitored for safety. Participants with WBC \<3000 but \>=2000 cells/mm\^3 or ANC \<1500 but \>=1000 cells/mm\^3 were to have study treatment suspended. Participants with WBC \<2000 or ANC \<1000 cells/mm\^3 were to be discontinued from study participation.

Change From Baseline in Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score at Day 28
Baseline, Day 28

The UHDRS is a clinical rating scale to provide a uniform assessment of the clinical features and course of Huntington Disease. The Total Motor Score (TMS) is 1 of the 6 components of UHDRS, includes 31 items, and ranges from a scale of 0 to 124 (higher scores indicate more severe disease).

Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Baseline
Baseline (Day 1)

C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.

Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 7
Day 7

C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.

Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 28
Day 28

C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.

Secondary Endpoints
Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria
Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Number of Participants With Adverse Events
Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Number of Participants With Serious Adverse Events
Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
20 mg PF-02545920 BIDEXPERIMENTAL20 mg PF-02545920 BID
5 mg PF-02545920 BIDEXPERIMENTAL5 mg PF-02545920 BID
Placebo BIDPLACEBO_COMPARATORMatching placebo
20 mg Arm Cohort AEXPERIMENTAL -
Placebo Arm Cohort APLACEBO_COMPARATOR -
5 mg Arm Cohort BEXPERIMENTAL -
Placebo Arm Cohort BPLACEBO_COMPARATOR -
Interventions
NameTypeDescription
PF-02545920DRUG20 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.
PlaceboOTHERMatching 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.
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Eligibility Criteria
Age Range30 Years — 65 Years
SexALL
Healthy VolunteersNo
Study Sites57

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 conditio...

Countries:United StatesCanadaGermanyPolandUnited KingdomFrance
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Competitive Landscape -Huntington's Disease 9 trials