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

Sommario: 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.


TIPOLOGIA STUDIO

Interventistico

FASE

Fase 3


TRATTAMENTO


OBIETTIVO PRIMARIO

  • Misura: Annualized bleeding rate (ABR) of treated bleeding events
  • Tempo: Through Observational Phase (6months) and Active Treatment Phase (12 months) for total of approximately 18 months
  • Descrizione: 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)
  • Misura: Incidence and severity of thrombotic events
  • Tempo: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
  • Descrizione:
  • Misura: Incidence of anti drug antibody [ADA] against PF-06741086
  • Tempo: Throughout Active Treatment Phase (12 months)
  • Descrizione:
  • Misura: Incidence of clinically significant persistent neutralizing antibody [NAb] against PF-06741086
  • Tempo: Throughout Active Treatment Phase (12 months)
  • Descrizione:
  • Misura: Incidence and severity of injection site reaction
  • Tempo: Throughout Active Treatment Phase (12 months)
  • Descrizione:
  • Misura: Number of participants with clinically significant changes from baseline in physical exam
  • Tempo: From Baseline through Observation and Active Treatment (approximately 18 months)
  • Descrizione:
  • Misura: Incidence of clinically significant laboratory value abnormalities
  • Tempo: From Screening through Observation and Active Treatment (approximately 18 months)
  • Descrizione:
  • Misura: Incidence of severe hypersensitivity and anaphylactic reactions
  • Tempo: From Screening through Observational and Active Treatment (approximately 18 months)
  • Descrizione:
  • Misura: Incidence of adverse events and serious adverse events
  • Tempo: From screening through Observation and Active treatment (approximately 18 months)
  • Descrizione:
  • Misura: Number of participants with clinically significant changes from baseline in vital signs
  • Tempo: From Baseline through Observation and Active Treatment (approximately 18 months)
  • Descrizione:
  • Misura: Incidence and severity of thromboticangiopathy
  • Tempo: Throughout Active Treatment Phase (12 months)
  • Descrizione:
  • Misura: Incidence of intravascular coagulation/consumption coagulopathy
  • Tempo: Throughout Active Treatment Phase (12 months)
  • Descrizione:

OBIETTIVO SECONDARIO

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

CRITERI DI ELIGIBILITA'

  • Criteri di inclusione e esclusione

    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.


SESSO

Maschi


ETA' MINIMA

Età Minima: 12 Years
Età Massima: 74 Years


LUOGO

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milano, 20122

Università degli Studi di Roma "Sapienza"-Policlinico Umberto I
Roma, 00161

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, 90127

Università degli Studi di Perugia, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della
Perugia, 06156

REFERENTE PER INFORMAZIONI

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com