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

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03938792
• Other study ID #: B7841005
• Secondary ID: 2018-003660-31
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 9, 2020
• Est. completion date: June 16, 2025

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 186
• Est. completion date: June 16, 2025
• Est. primary completion date: June 16, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

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.

Locations

Country	Name	City	State
Bulgaria	National Specialized Hospital for the Active Treatment of Hematological Diseases - EAD, Sofia	Sofia
Bulgaria	UMHAT "Prof.Dr. Stoyan Kirkovich"	Stara Zagora
Canada	McMaster Children's Hospital	Hamilton	Ontario
Canada	McMaster Children's Hospital	Hamilton	Ontario
Canada	McMaster University	Hamilton	Ontario
Canada	McMaster University Medical Centre - Hamilton Health Sciences	Hamilton	Ontario
Canada	The Hospital For Sick Children	Toronto	Ontario
China	Beijing Children's Hospital, Capital Medical University	Beijing
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Institute of Hematology, Chinese Academy of Medical Sciences	Tianjin	Tianjin
Croatia	Klinicki bolnicki centar Zagreb	Zagreb
France	Hôpital Necker Enfants Malades	Paris
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
India	Sahyadri Clinical Research and Development Center	Pune	Maharashtra
India	Sahyadri Super Speciality Hospital	Pune	Maharashtra
India	Nirmal Hospital Pvt, Ltd	Surat	Gujarat
India	Christian Medical College	Vellore	Tamil NADU
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	Milan
Italy	Università degli Studi di Perugia, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della	Perugia
Italy	Università degli Studi di Roma "Sapienza"-Policlinico Umberto I	Roma	RM
Japan	Tokyo Metropolitan Children's Medical Center	Fuchu	Tokyo
Japan	Hiroshima University Hospital	Hiroshima
Japan	Saitama Medical University Hospital	Iruma-gun	Saitama
Japan	Nagoya University Hospital - Transfusion Medicine	Nagoya	Aichi
Japan	Sapporo Tokushukai Hospital	Sapporo	Hokkaido
Japan	Ogikubo Hospital	Suginami-ku	Tokyo
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Kyung Hee University Hospital At Gangdong	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Centro Multidisciplinario para el Desarrollo Especializado de la Inv. Clínica en Yucatán, S.C.P.	Mérida	Yucatán
Mexico	Hospital Universitario "Dr Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON
Oman	Sultan Qaboos University Hospital	Muscat
Russian Federation	FGBOU VO "Samara State Medical University" of MoH of Russia	Samara
Saudi Arabia	King Abdulaziz University Hospital	Jeddah
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Institute for Mother and Child healthcare "Dr Vukan Cupic"	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Nis	Nis
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
Spain	Hospital Universitario A Coruna	A Coruna
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	ChangHua Christian Hospital	Changhua City	Changhua County
Taiwan	Taichung Veterans General Hospital	Taichung
Turkey	Acibadem Adana Hospital	Adana
Turkey	Gazi University Health Research and Practice Center Gazi Hospital	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Gaziantep University Sahinbey Research and Training Hospital	Gaziantep
Turkey	Istanbul University Oncology Institute	Istanbul
Turkey	Dr. Behcet Uz Child Diseases Surgery Education and Research Hospital	Izmir
Turkey	Ege University Medical Faculty	Izmir
Turkey	Erciyes University Medical Faculty	Kayseri
Turkey	Ondokuz Mayis University Medical Faculty	Samsun
Turkey	Karadeniz Technical University Medical Faculty	Trabzon
United States	University of Iowa	Iowa City	Iowa
United States	Northwell Health HTC	New Hyde Park	New York
United States	Washington Institute for Coagulation	Seattle	Washington
United States	USF Health Morsani Center For Advanced Healthcare	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  China,  Croatia,  France,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Oman,  Russian Federation,  Saudi Arabia,  Serbia,  South Africa,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized bleeding rate (ABR) of treated bleeding events	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)	Through Observational Phase (6months) and Active Treatment Phase (12 months) for total of approximately 18 months
Primary	Incidence and severity of thrombotic events		Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Primary	Incidence of anti drug antibody [ADA] against PF-06741086		Throughout Active Treatment Phase (12 months)
Primary	Incidence of clinically significant persistent neutralizing antibody [NAb] against PF-06741086		Throughout Active Treatment Phase (12 months)
Primary	Incidence and severity of injection site reaction		Throughout Active Treatment Phase (12 months)
Primary	Number of participants with clinically significant changes from baseline in physical exam		From Baseline through Observation and Active Treatment (approximately 18 months)
Primary	Incidence of clinically significant laboratory value abnormalities		From Screening through Observation and Active Treatment (approximately 18 months)
Primary	Incidence of severe hypersensitivity and anaphylactic reactions		From Screening through Observational and Active Treatment (approximately 18 months)
Primary	Incidence of adverse events and serious adverse events		From screening through Observation and Active treatment (approximately 18 months)
Primary	Number of participants with clinically significant changes from baseline in vital signs		From Baseline through Observation and Active Treatment (approximately 18 months)
Primary	Incidence and severity of thromboticangiopathy		Throughout Active Treatment Phase (12 months)
Primary	Incidence of intravascular coagulation/consumption coagulopathy		Throughout Active Treatment Phase (12 months)
Secondary	Incidence of joint bleeds		Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Secondary	Incidence of spontaneous bleeds		Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Secondary	Incidence of target joint bleeds		Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Secondary	Incidence of total bleeds (treated and untreated)		Through Observational and Active Treatment Phases (18 Months)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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