PROPHYLAXIS STUDY OF PF-06741086 IN ADOLESCENT AND ADULT HEMOPHILIA PATIENTS WITH OR WITHOUT INHIBITORS
- Conditions
- Hemophilia A or BMedDRA version: 20.0Level: LLTClassification code 10060613Term: Hemophilia A (Factor VIII)System Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10060614Term: Hemophilia B (Factor IX)System Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-003660-31-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 106
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 inclusive, 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).
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 outside the US and Canada receiving routine prophylaxis (defined as treatment by IV injection of factor concentrate to prevent anticipated 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 (For investigator sites in the US and Canada only: See Appendix 7 of the protocol for details).
OR
• Participants with on-demand treatment regimen with =6 acute bleeding episodes (spontaneous and/or traumatic) that required coagulation factor infusion during the 6 months period prior to Screening 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 30 days prior to Baseline of Observational Phase, Enrollment into Observational Phase.
• Participants with on-demand treatment regimen with =6 bleeding episodes (spontaneous and/or traumatic) necessitating treatment with bypass factor for at least 6 months prior to screening 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 caregiver capable of giving signed informed consent (or minor assent, when applicable) as described in Appendix 1 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) 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 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
Medical Conditions
1. Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis (Common Terminology Criteria for Adverse Events [CTCAE]13 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.
5. Abnormal hematology values as defined by the following laboratory tests at Screening:
a. Platelet count <100,000/uL
b. Fibrinogen level c. Hemoglobin level <10 g/dL
6. Abnormal coagulation activity as defined by the following laboratory results at Screening:
a. Prothrombin time (PT) >1.25 × ULN.
7. 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.
8. QTc >450 msec for male participants or QTc >480 msec in participants with bundle branch block
Prior/Concomitant Therapy
9. Current routine prophylaxis with bypassing agent (eg, aPCC, Prothrombin Complex Concentrates [PCC], and/or rFVIIa) or no coagulation factor-replacement therapy (eg, emicizumab).
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 and/or during study participation.
Diagnostic assessments
13. CD4 cell count =200/uL if human immunodeficiency virus (HIV)-positive
14. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
Other Exclusions
15. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, incl
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