Study of the Efficacy and Safety PF-06741086 in Adult and Teenage Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03938792

Collaborator

(none)

145

Enrollment

Locations

Arm

54.6

Anticipated Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Treatment with PF-06741086 is anticipated to demonstrate a clinically relevant advantage and/or a major contribution to patient care in comparison to current methods of treatment for hemophilia A or B because it works differently than factor replacement products and will work in the presence of inhibitors. The potential for once weekly (QW) subcutaneous (SC) administration provides for treatment options in the absence of reliable vascular access, increased convenience and may enable better compliance. Combined, these qualities should result in a reduction of bleeding episodes.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A Hemophilia B	Drug: PF-06741086	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

145 participants

Allocation:

N/A

Intervention Model:

Crossover Assignment

Intervention Model Description:

This is a one way Cross-Over Prevention study with 1 Arm that has No masking.This is a one way Cross-Over Prevention study with 1 Arm that has No masking.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Study in Adolescent and Adult Severe (Coagulation Factor Activity <1%) Hemophilia A Participants With or Without Inhibitors or Moderately Severe to Severe Hemophilia B Participants (Coagulation Factor Activity ≤2%) With or Without Inhibitors Comparing Standard Treatment to PF-06741086 Prophylaxis

Actual Study Start Date :

Mar 9, 2020

Anticipated Primary Completion Date :

Sep 27, 2024

Anticipated Study Completion Date :

Sep 27, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-06741086 Participants will be assigned to treatment with PF-06741086 after a 6 month Observation Phase on their current hemophilia regimen.	Drug: PF-06741086 300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria.

Arm

Intervention/Treatment

Experimental: PF-06741086

Participants will be assigned to treatment with PF-06741086 after a 6 month Observation Phase on their current hemophilia regimen.

Drug: PF-06741086

300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria.

Outcome Measures

Primary Outcome Measures

Annualized bleeding rate (ABR) of treated bleeding events [Through Observational Phase (6months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Derived for each subject for each treatment period by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25)
Incidence and severity of thrombotic events [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Incidence of anti drug antibody [ADA] against PF-06741086 [Throughout Active Treatment Phase (12 months)]
Incidence of clinically significant persistent neutralizing antibody [NAb] against PF-06741086 [Throughout Active Treatment Phase (12 months)]
Incidence and severity of injection site reaction [Throughout Active Treatment Phase (12 months)]
Number of participants with clinically significant changes from baseline in physical exam [From Baseline through Observation and Active Treatment (approximately 18 months)]
Incidence of clinically significant laboratory value abnormalities [From Screening through Observation and Active Treatment (approximately 18 months)]
Incidence of severe hypersensitivity and anaphylactic reactions [From Screening through Observational and Active Treatment (approximately 18 months)]
Incidence of adverse events and serious adverse events [From screening through Observation and Active treatment (approximately 18 months)]
Number of participants with clinically significant changes from baseline in vital signs [From Baseline through Observation and Active Treatment (approximately 18 months)]
Incidence and severity of thromboticangiopathy [Throughout Active Treatment Phase (12 months)]
Incidence of intravascular coagulation/consumption coagulopathy [Throughout Active Treatment Phase (12 months)]

Secondary Outcome Measures

Incidence of joint bleeds [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Incidence of spontaneous bleeds [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Incidence of target joint bleeds [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Incidence of total bleeds (treated and untreated) [Through Observational and Active Treatment Phases (18 Months)]
Change from baseline in the Hemophilia Joint Health Score (HJHS) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Change from baseline in (Haemophilia Adult Quality of Life Questionnaire (Haem-A-QoL) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Change from baseline in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Change from baseline in Hemophilia Adult Activities List (HAL) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Change from baseline in Hemophilia Pediatric Activities List (PedHAL) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Patient Global Impression of Change - Hemophilia (PGIC-H) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]
Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) [Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 74 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria

Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B with a minimum weight of 35 kg at screening.
Participant or legally authorized representative, or participant's caregiver capable of giving signed informed consent (or minor assent, when applicable).

Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:

No detectable or documented history of inhibitors
Participants on FVIII/FIX routine prophylaxis who have demonstrated at least 80% compliance with scheduled prophylaxis regimen during 6 months prior to enrollment and are willing to continue to receive routine prophylaxis treatment with FVIII/FIX replacement during the Observational Phase.
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 and willing to continue to receive on demand treatment during the Observational Phase.

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 enrolment into the Observational Phase
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.
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 prior agreement from the Pfizer Medical Monitor
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 agreement from the Pfizer medical monitor.

Exclusion Criteria

Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis or ischemic disease
Known planned surgical procedure during the planned study period.
Known hemostatic defect other than hemophilia A or B.
Abnormal renal or hepatic function
Current unstable liver or biliary disease
Abnormal hematologic parameters
Other 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,
Current routine prophylaxis with bypassing agent or non-coagulation non-factor- replacement therapy, or any previous treatment with a gene therapy product for treatment of hemophilia (participants treated with prophylaxis using bypassing agents or who had prior treatment with non-factor products may be considered on a case-by-case basis).
Regular, concomitant therapy with immunomodulatory drugs
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 treatment with study intervention during the Active Treatment Phase
Previous exposure to PF 06741086 during participation in studies B7841002 and B7841003.
Participation in other studies involving investigational drug(s) or investigational vaccines within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry and/or during study participation.
CD4 cell count ≤200/uL if human immunodeficiency virus (HIV)-positive
Screening ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention.
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, including their family members, directly involved in the conduct of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USF Health Morsani Center For Advanced Healthcare	Tampa	Florida	United States	33612
2	University of Iowa	Iowa City	Iowa	United States	52242
3	Northwell Health HTC	New Hyde Park	New York	United States	11040
4	National Specialized Hospital for the Active Treatment of Hematological Diseases - EAD, Sofia	Sofia		Bulgaria	1756
5	UMHAT "Prof.Dr. Stoyan Kirkovich"	Stara Zagora		Bulgaria	6003
6	McMaster Children's Hospital	Hamilton	Ontario	Canada	L8N 3Z5
7	McMaster University Medical Centre - Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
8	McMaster University	Hamilton	Ontario	Canada	L8S 4K1
9	The Hospital For Sick Children	Toronto	Ontario	Canada	M5G 1X8
10	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong	China	510515
11	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou	China	550004
12	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi	China	306113
13	Institute of Hematology, Chinese Academy of Medical Sciences	Tianjin	Tianjin	China	300020
14	Beijing Children's Hospital, Capital Medical University	Beijing		China	100045
15	Klinicki bolnicki centar Zagreb	Zagreb		Croatia	10000
16	Hôpital Necker Enfants Malades	Paris		France	75015
17	Prince of Wales Hospital	Hong Kong		Hong Kong
18	Queen Mary Hospital	Hong Kong		Hong Kong
19	Nirmal Hospital Pvt, Ltd	Surat	Gujarat	India	395002
20	Sahyadri Clinical Research and Development Center	Pune	Maharashtra	India	411004
21	Sahyadri Super Speciality Hospital	Pune	Maharashtra	India	411004
22	Christian Medical College	Vellore	Tamil NADU	India	632004
23	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	Milan	Italy	20122
24	Università degli Studi di Roma "Sapienza"-Policlinico Umberto I	Roma	RM	Italy	00161
25	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo		Italy	90127
26	Università degli Studi di Perugia, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della	Perugia		Italy	06156
27	Nagoya University Hospital - Transfusion Medicine	Nagoya	Aichi	Japan	466-8560
28	Sapporo Tokushukai Hospital	Sapporo	Hokkaido	Japan	004-0041
29	Tokyo Metropolitan Children's Medical Center	Fuchu	Tokyo	Japan	183-8561
30	Ogikubo Hospital	Suginami-ku	Tokyo	Japan	167-0035
31	Hiroshima University Hospital	Hiroshima		Japan	734-8551
32	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
33	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
34	Kyung Hee University Hospital at Gangdong	Seoul		Korea, Republic of	05278
35	Hospital Universitario "Dr Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON	Mexico	64460
36	Centro Multidisciplinario para el Desarrollo Especializado de la Inv. Clínica en Yucatán, S.C.P.	Mérida	Yucatán	Mexico	97130
37	Sultan Qaboos University Hospital	Muscat		Oman	123
38	FGBOU VO "Samara State Medical University" of MoH of Russia	Samara		Russian Federation	443079
39	King Abdulaziz University Hospital	Jeddah		Saudi Arabia	21589
40	King Faisal Specialist Hospital & Research Center	Riyadh		Saudi Arabia
41	Clinical Center of Serbia	Belgrade		Serbia	11000
42	Institute for Mother and Child healthcare "Dr Vukan Cupic"	Belgrade		Serbia	11000
43	Clinical Center Kragujevac	Kragujevac		Serbia	34000
44	Clinical Center Nis	Nis		Serbia	18000
45	Hospital Universitario A Coruna	A Coruna		Spain	15006
46	Hospital Universitario Vall d´Hebron	Barcelona		Spain	08035
47	Hospital Universitario La Paz	Madrid		Spain	28046
48	Hospital Universitario de Salamanca	Salamanca		Spain	37007
49	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
50	ChangHua Christian Hospital	Changhua City	Changhua County	Taiwan	500
51	Taichung Veterans General Hospital	Taichung		Taiwan	40705
52	Acibadem Adana Hospital	Adana		Turkey	01130
53	Hacettepe University Medical Faculty	Ankara		Turkey	06230
54	Gazi University Health Research and Practice Center Gazi Hospital	Ankara		Turkey	06500
55	Akdeniz University Medical Faculty	Antalya		Turkey	07060
56	Gaziantep University Sahinbey Research and Training Hospital	Gaziantep		Turkey	27310
57	Istanbul University Oncology Institute	Istanbul		Turkey	34093
58	Ege University Medical Faculty	Izmir		Turkey	35040
59	Dr. Behcet Uz Child Diseases Surgery Education and Research Hospital	Izmir		Turkey	35210
60	Erciyes University Medical Faculty	Kayseri		Turkey	38039
61	Ondokuz Mayıs University Medical Faculty	Samsun		Turkey	55280
62	Karadeniz Technical University Medical Faculty	Trabzon		Turkey	61080