PROPHYLAXIS STUDY OF PF-06741086 IN ADOLESCENT AND ADULT HEMOPHILIA PATIENTS WITH OR WITHOUT INHIBITORS

Phase 1

Conditions: Hemophilia A or B
MedDRA version: 20.0Level: LLTClassification code 10060613Term: Hemophilia A (Factor VIII)System Organ Class: 100000004850
MedDRA version: 20.0Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 100000004850
MedDRA version: 20.0Level: LLTClassification code 10060614Term: Hemophilia B (Factor IX)System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2018-003660-31-IE

Lead Sponsor: Pfizer Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 145

Inclusion Criteria

Participants are eligible to be included in the study only if all of the
following criteria apply:
Age
1. Participant must be male and 12 to <75 years of age with a minimum
body weight of 35 kg at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Participants with a diagnosis of severe hemophilia A or B (FVIII or FIX
activity <1%, respectively) documented by a clinical laboratory prior to
Enrollment. The severity of hemophilia may be confirmed either by
documented historical evidence from a clinical laboratory prior to
Screening or by factor activity obtained from a clinical laboratory (which
may include the central laboratory for this study) prior to Enrollment.
3. Participants who are enrolled into the Non-Inhibitor Cohort must also
meet the following criteria:
• No detectable or documented history of inhibitors (=0.6 BU/mL or
greater than the upper limit of normal [ULN] for the testing laboratory)
against FVIII or FIX prior to enrollment (Baseline of Observational
Phase).
• Participants receiving routine prophylaxis (defined as treatment by IV
injection of factor concentrate to prevent bleeding) treatment with FVIII/FIX replacement, have demonstrated at least 80% compliance
with scheduled prophylaxis regimen during 6 months prior to
enrollment, and willing to continue to receive routine prophylaxis
treatment with FVIII/FIX replacement during the Observational Phase.
(OR)
• Participants with on-demand treatment regimen with =6 acute
bleeding episodes (spontaneous or traumatic) that required coagulation
factor infusion during the 6 months period prior to Enrollment into
Observational Phase and willing to continue to receive on demand
treatment during the Observational Phase. Surgical bleeding episodes
do not apply to this criterion.
4. Participants who are enrolled into the Inhibitor Cohort must also meet
the following criteria:
• Documentation of current high titer inhibitor (=5 BU/mL); or current
low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement
and with FVIII or FIX recovery <60% of expected within previous 6
months prior to Enrollment into Observational Phase.
• Participants who have documented inhibitors while on factorreplacement
therapy but who do not meet the quantitative inhibitor
criteria described in the prior bullet at the time of Screening (eg,
participant with a previously documented high-titer inhibitor (=5
BU/mL) and whose condition precludes re-challenge with FVIII or FIX
replacement) may be considered for eligibility on a case-by-case basis
with discussion and endorsement from the Pfizer Medical Monitor.
• Participants with on-demand treatment regimen with =6 bleeding
episodes (spontaneous or traumatic) necessitating treatment with
bypass factor during the 6 months prior to Enrollment into Observational
Phase and willing to continue to receive on-demand treatment during
the Observational Phase. Surgical bleeding episodes do not apply to this
criterion.
Sex
5. Male
Informed Consent
6. Participant or legally authorized representative, or participant's
caregiver capable of giving signed informed consent (or minor assent,
when applicable) as described in Appendix 1 which includes compliance
with the requirements and restrictions listed in the informed consent
document (ICD) and in this protocol.

Are the trial subjects under 18? yes
Number of subjects for this age range: 29
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 104
F.1.3

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Previous or current treatment for or history of coronary artery
diseases, venous or arterial thrombosis (Common Terminology Criteria
for Adverse Events [CTCAE] Grade >1), or ischemic disease (except
treatment for catheter associated thrombosis).
2. Known planned surgical procedure during the planned study period.
3. Known hemostatic defect other than hemophilia A or B.
4. Abnormal renal or hepatic function as defined by the following
laboratory results at Screening:
a. Alanine transaminase (ALT) >2 × upper limit of normal (ULN)
b. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if
bilirubin is fractionated and direct bilirubin <35%)
c. Current unstable liver or biliary disease per investigator assessment
defined by the presence of ascites, encephalopathy, coagulopathy,
hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice,
or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -
eg, presence of hepatitis B surface antigen [HBsAg] or positive hepatitis
C antibody test result at screening or within 3 months prior to starting
study intervention) is acceptable if the participant otherwise meets
entry criteria
d. Serum albumin less than the lower limit of normal (LLN).
e. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (see
Appendix 10.2.1 for formulas used in eGFR calculation).
5. Abnormal hematology values as defined by the following laboratory
tests at Screening:
a. Platelet count <100,000/uL
b. Hemoglobin level <10 g/dL
6. Other acute or chronic medical or psychiatric condition including
recent (within the past year) or active suicidal ideation or behavior 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 participant inappropriate for entry into this
study.
7. QTc >450 msec for male participants or QTc >480 msec in participants
with bundle branch block.
8. Individuals with hypersensitivity or an allergic reaction to hamster
protein or other components of the study intervention.
Prior/Concomitant Therapy
9. Current routine prophylaxis with bypassing agent (eg, aPCC, BYCLOT,
Prothrombin Complex Concentrates [PCC], or rFVIIa), non-coagulation
non-factor replacement therapy (eg, emicizumab), or any previous
treatment with a gene therapy product for treatment of hemophilia.
• Potential participants who have previously received investigational
non-factor-based hemophilia therapy (eg, fitusiran) will be considered
on a case-by-case basis, only after discussion and agreement between
the investigator and the Pfizer Medical Monitor.
10. Regular, concomitant therapy with immunomodulatory drugs (eg, IV
immunoglobulin [IVIG], and routine systemic corticosteroids,
rituximab).
11. Ongoing or planned use of immune tolerance induction during the
Observational Phase or Active Treatment Phase, or prophylaxis with
FVIII or FIX replacement during the Active Treatment Phase.
Prior/Concurrent Clinical Study Experience
12. Participation in other studies involving investigational drug(s) within
30 days (or as determined by local requirements) or 5 half-lives prior to
study entry or during study participation.
13. Previous exposure to P

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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