PROPHYLAXIS STUDY OF PF-06741086 IN ADOLESCENT AND ADULT HEMOPHILIA PARTICIPANTS 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-BG
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-29
• Last Update Posted: 29 November 2021

Recruitment & Eligibility

• Status: A
• Sex: Male
• Target Recruitment: 174

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 moderately severe to severe hemophilia B (FVIII activity <1% or FIX activity =2%, 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 factor-replacement 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 agreement from the Pfizer medical monitor.
• Hemophilia A participants with on-demand treatment regimen with =6 bleeding episodes or hemophilia B participants with =4 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.
•Participants who meet the bleeding criteria noted above and who are on routine prophylaxis (defined as treatment by IV injection of bypass factor to prevent bleeding) and have demonstrated at least 80% compliance with scheduled prophylaxis regimen during the 6 months prior to enrollment, may be considered for eligibility on a case-by-case basis with discussion and agreem

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 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 Section 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. QTcF >450 msec for male participants or QTcF >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.
• Participants with inhibitors who are being treated using a prophylaxis treatment regimen with a bypass agent will be considered on a case-by-case basis, only after discussion and agreement between the investigator and the Pfizer medical monitor.
• Participants who have previously received non-factor-based hemophilia therapy (eg, fitusiran, concizumab, emicizumab) 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 at any time after initiation of trea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified