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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2014-001291-56-GB
• Date of registration: 21/07/2014
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public 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
• Scientific 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
• Date of first enrolment: 24/04/2015
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001291-56
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Germany, Poland, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent(s) document(s) indicating that the subject has been informed of all pertinent aspects of the study.
2. Males or females between the age of 30 years and 65 years (inclusive)
3. Diagnosis of HD based on characteristic clinical findings, including presence of chorea, and genetic confirmation with the detection of an expansion of = 36 CAG trinucleotide repeats in the huntingtin gene (Htt)
4. UHDRS Total Motor Score (TMS) equal or greater than 10
5. UHDRS total functional capacity (TFC) equal or greater than 7
6. Male and female subjects capable of having children and/or at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 28 days (90 days for males) after the last dose of assigned treatment. A subject is capable of having children if, in the opinion of the investigator, he/she is sexually active and biologically capable.
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure; or
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. The subset of subjects participating in the MRI imaging cohort must be willing and able to comply with scheduled MRI study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
2. Evidence or history of:
a. Clinically significant neurologic disorder other than Huntington’s disease. This also includes subjects with previous history of epilepsy or seizures (except childhood febrile seizures), stroke, head injury with significant neurologic sequelae.
b. Other severe acute psychiatric condition, mania and/or psychosis.
c. Attempted suicide or suicidal ideation with intention or plan, which required hospital admission and/or change of level of care within 12 months prior to Screening. For subjects who score = 3 on the suicidal ideation item of the Problem Behaviors Assessment or answer “Yes” to the C-SSRS questions 4 or 5, a risk assessment should be done by a qualified mental health professional (a psychiatrist or licensed PhD level clinical psychologist) to assess whether it is safe for the subject to participate in the study (See Suicidality Risk Assessment). In addition, subjects deemed by the investigator to be at significant risk of suicidal or violent behavior should be excluded.
3. Evidence or history of any clinically significant conditions affecting one of the following systems:
a. Hepatic: subject with evidence or history of significant hepatic disorder, including acute or chronic hepatitis B and acute hepatitis C, with liver function tests results higher than the normal limits. Subjects with positive hepatitis C antibody and normal (within the lab normal ranges) liver functions tests can be included in the study.
b. Renal
c. Endocrine (excluding adequately controlled hypothyroidism and hyperthyroidism and controlled type 2 diabetes with fasting blood glucose = 180 mg/dl and hemoglobin A1c (HgA1c) = 8 at Screening )
d. Pulmonary
e. Hematological
f. Gastrointestinal (including any condition possibly affecting drug absorption, eg, gastrectomy, gastric bypass)
g. Immunological, including positivity for human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)
h. Severe allergic diseases (excluding untreated, asymptomatic, seasonal and environmental allergies at time of dosing)
i. Any history of malignant tumors and treatment within the previous year
4. Subjects with:
a. WBC = 3500/mm3 OR ANC = 2000/mm3
b. History of neutropenia, including benign ethnic neutropenia, clozapine induced agranulocytosis or granulocytopenia
c. History of myeloproliferative disorders (primary myelofibrosis, polycythemia vera, essential thrombocythemia, chronic eosinophilic leukemia/hypereosinophilic syndrome, systemic mastocytosis)
5. Evidence or history of clinically significant cardiovascular disease, including:
a. Uncontrolled hypertension (sitting or supine diastolic blood pressure > 95 mmHg and/or sitting or supine systolic blood pressure > 170 mmHg with or without treatment)
b. Evidence of orthostatic symptoms (eg. dizziness upon standing) or systolic blood pressure

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

HUNTINGTON’S DISEASE
MedDRA version: 17.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 17.0 Level: LLT Classification code 10020469 Term: Huntington's chorea System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Code: PF-02545920
Pharmaceutical Form: Tablet
INN or Proposed INN: not available
Current Sponsor code: PF-02545920
Other descriptive name: PF-02545920
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: • To assess the efficacy of 26-week oral daily dosing with PF-02545920 on motor function in subjects with HD.

Secondary Objective: • To assess the safety and tolerability of two oral doses (5 mg and 20 mg BID) of PF-02545920 in subjects with HD.
• To assess the efficacy of 13 and 26-week oral daily dosing with PF-02545920 on chorea severity in subjects with HD.
• To assess whether treatment with PF-02545920 can improve overall clinical impression in subjects with HD following multiple doses (13 and 26 weeks).

Primary end point(s): • Change from baseline in the Total Motor Score (TMS) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 26 weeks treatment.

Timepoint(s) of evaluation of this end point: after 26 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Number and proportion of subjects with adverse events, clinical laboratory parameters: at each visit.
• Assessment of vital signs, ECG parameters: v1, v2, v5, v7, v9
• White blood count (WBC) and absolute neutrophil count (ANC): at each visit.
• Abnormal laboratory findings from baseline: at each visit.
• Frequency and severity of adverse events related to extrapyramidal symptoms (EPS) including dystonia and akathisia, as assessed by the investigator: at each visit.
• C SSRS: at each visit.
• Change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS: after 13 and 26 weeks of treatment.
• Clinical Global Impression-Improvement score: after 13 and 26 weeks of treatment.

Secondary end point(s): • Adverse events, weight, vital signs (pulse, blood pressure and body temperature), physical examination, neurological examination, electrocardiogram (ECG) and clinical laboratory findings (hematology, biochemistry and urinalysis). The endpoints are:
• The number and proportion of subjects with adverse events.
• Assessment of clinical laboratory parameters.
• Assessment of vital signs.
• Assessment of ECG parameters.
• White blood count (WBC) and absolute neutrophil count (ANC) at each visit.
• Abnormal laboratory findings from baseline.
• Frequency and severity of adverse events related to extrapyramidal symptoms (EPS) including dystonia and akathisia, as assessed by the investigator.
• C SSRS (suicide severity assessment).
• Change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS after 13 and 26 weeks of treatment.
• Clinical Global Impression-Improvement score after 13 and 26 weeks of treatment.

Secondary ID(s)

A8241021

118,646

2014-001291-56-DE

Source(s) of Monetary Support

Pfizer Inc., 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 23/09/2017
• Date Completed: 04/10/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001291-56/results