AN OPEN LABEL EXTENSION STUDY TO INVESTIGATE THE LONG TERM SAFETY, TOLERABILITY AND EFFICACY OF PF-02545920 IN SUBJECTS WITH HUNTINGTON’S DISEASE WHO PREVIOUSLY COMPLETED STUDY A8241021

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2014-004900-31-DE
• Date of registration: 13/02/2015
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: AN OPEN LABEL EXTENSION STUDY TO INVESTIGATE THE LONG TERM SAFETY, TOLERABILITY AND EFFICACY OF PF-02545920 IN SUBJECTS WITH HUNTINGTON’S DISEASE WHO PREVIOUSLY COMPLETED STUDY A8241021
• Scientific title: AN OPEN LABEL EXTENSION STUDY TO INVESTIGATE THE LONG TERM SAFETY, TOLERABILITY AND EFFICACY OF PF-02545920 IN SUBJECTS WITH HUNTINGTON’S DISEASE WHO PREVIOUSLY COMPLETED STUDY A8241021
• Date of first enrolment: 27/05/2015
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004900-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• 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 document indicating that the subject has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Subjects must have completed Study A8241021 and, in the opinion of the investigator and sponsor, have been compliant with the STUDY PROCEDURES, Lifestyle Guidelines and study treatment.
4. Only subjects who were part of the MRI cohort in study A8241021 are eligible for the MRI assessments.
5. Males or females between the age of 30 years and 66 years (inclusive).
6. 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).
7. Male and female subjects of childbearing potential and 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.
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.
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. Participation in study(ies) involving investigational drug(s) (Phases 1-4) other than PF-02545920 within the past 9 months before the current study begins and/or during study participation.
3. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
4. 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. 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 (eg, 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. Attempted suicide or suicidal ideation with intention or plan, which required hospital admission and/or change of level of care within 15 months prior to Screening should be discussed with medical monitor or clinician before proceeding.
5. Evidence or history of any clinically significant conditions which affect one of the following systems and which were used as exclusion criteria in preceding A8241021 study:
a. Renal.
b. Endocrine.
c. Pulmonary.
d. Hematological.
e. Gastrointestinal (including any condition possibly affecting drug absorption, eg, gastrectomy, gastric bypass).
f. Immunological, including positivity for human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS).
g. Severe allergic diseases (excluding untreated, asymptomatic, seasonal and environmental allergies at time of dosing).
h. Any history of malignant tumors and treatment within the previous 15 months.
6. Subjects with:
a. WBC = 3500/mm3 OR ANC = 2000/mm3 anytime in study A8241021 which were not approved as acceptable for enrollment in study A8241022 by the sponsor study clinician or sponsor medical monitor. These cases should be discussed with the sponsor medical monitor or clinician prior to submitting subject for an eligibility approval.
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).
7. 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

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

Health Condition(s) or Problem(s) studied

HUNTINGTON'S DISEASE
MedDRA version: 17.1 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 17.1 Level: LLT Classification code 10020469 Term: Huntington's chorea System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

Intervention(s)

Product Name: 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)

Timepoint(s) of evaluation of this end point: - adverse events: v3-v9
- Assessment of clinical laboratory parameters: v2-v9
- Assessment of vital signs: v3, v4, v5, v7, v9
- Assessment of ECG parameters: v2, v5-v8
- White blood count (WBC) and absolute neutrophil count (ANC) at each visit
- Abnormal laboratory findings from baseline: v2-v9
- Frequency and severity of adverse events related to extrapyramidal symptoms (EPS) including dystonia and akathisia, as assessed by the investigator: v3-v9
- C-SSRS (suicide severity assessment): v2-v9

Secondary Objective: - To assess motor function after 6 and 12 month oral dosing with 20 mg BID of PF-02545920 in subjects with HD.
- To assess the efficacy of 6 and 12 month oral dosing with 20 mg BID of PF-02545920 on chorea severity in subjects with HD.
- To assess whether 6 and 12 month oral dosing with 20 mg BID of PF-02545920 can improve the overall clinical impression in subjects with HD.

Primary 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).

Main Objective: - To assess long-term safety and tolerability of 20 mg BID of PF-02545920 in subjects with HD.

Secondary Outcome(s)

Secondary end point(s): - Change from baseline in the Total Motor Score (TMS) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 6 and 12 months of treatment.
- Change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS after 6 and 12 months of treatment.
- Clinical Global Impression-Improvement score after 6 and 12 months of treatment.

Timepoint(s) of evaluation of this end point: - Change from baseline in the Total Motor Score (TMS) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 6 and 12 months of treatment.
- Change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS after 6 and 12 months of treatment.
- Clinical Global Impression-Improvement score after 6 and 12 months of treatment.

Secondary ID(s)

118,646

A8241022

Source(s) of Monetary Support

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