Moroctocog Alfa (AF-CC) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Hemophilia A Patients
Condition: Hemophilia A
MeSH terms: Hemophilia A
Study type: Interventional
Phase: Phase 4

Summary: 
      Moroctocog-alfa (AF-CC) is indicated for the control and prevention of hemorrhagic episodes
      and for routine and surgical prophylaxis in patients with hemophilia A (congenital factor
      VIII deficiency or classic hemophilia). The current single country, multi-centric, open
      label, non-randomized pragmatic clinical trial is a post-approval study to fulfill the
      Central Drugs Standard Control Organization (CDSCO) request for supplementary information
      relating to the use of moroctocog-alfa (AF-CC) in Indian subjects with hemophilia A.

      The primary objective of study is to study the safety of moroctocog alfa (AF-CC) when
      administered for prophylaxis with respect to incidence of FVIII inhibitor development. The
      secondary objectives are to evaluate the incidence of adverse events (AEs) and serious
      adverse events (SAEs) in subjects receiving moroctocog alfa (AF-CC) prophylaxis, to evaluate
      the efficacy of moroctocog alfa (AF-CC) during a prophylaxis regimen, to evaluate the total
      annualized consumption of moroctocog alfa (AF-CC) by subjects following a prophylaxis
      regimen, to evaluate the efficacy of moroctocog alfa (AF-CC) for the treatment of
      breakthrough bleeding episodes (on-demand treatment) while following a prophylaxis regimen.

      Fifty male subjects aged >/= 12 years to ≤65 years with moderate or severe hemophilia A will
      be enrolled in the study. The subjects will be selected based on protocol specified
      eligibility criteria. The overall treatment duration for each subject will be up to 8 weeks,
      with up to a 4-week screening period and a subsequent post-treatment 28-day safety
      observation period. Subjects are requested to continue in the study until 24 exposure days
      (EDs) or a period of up to 8 weeks on moroctocog alfa (AF-CC) treatment had occurred
      (whichever occurs first). Efficacy and safety assessments will be performed as specified in
      the protocol.
    

Detailed description: 
      Moroctocog-alfa (AF-CC) is indicated in India for the control and prevention of hemorrhagic
      episodes and for routine and surgical prophylaxis in patients with hemophilia A (congenital
      factor VIII deficiency or classic hemophilia). The current protocol outlines a post-approval
      study to fulfill the Central Drugs Standard Control Organization (CDSCO) written request for
      supplementary information relating to the use of moroctocog-alfa (AF-CC) in Indian subjects
      with hemophilia A. The additional information will include safety and efficacy of
      moroctocog-alfa (AF-CC) in Indian subjects with a diagnosis of congenital moderate or severe
      hemophilia A (FVIII:C ≤5%). The primary objective is to study the safety of moroctocog alfa
      (AF-CC) when administered for prophylaxis with respect to incidence of FVIII inhibitor
      development. The secondary objectives are to evaluate the incidence of adverse events (AEs)
      and serious adverse events (SAEs) in subjects receiving moroctocog alfa (AF-CC) prophylaxis,
      to evaluate the efficacy of moroctocog alfa (AF-CC) during a prophylaxis regimen, to evaluate
      the total annualized consumption of moroctocog alfa (AF-CC) by subjects following a
      prophylaxis regimen and to evaluate the efficacy of moroctocog alfa (AF-CC) for the treatment
      of breakthrough bleeding episodes (on-demand treatment) while following a prophylaxis
      regimen. The primary endpoint will be the proportion of subjects who develop FVIII inhibitor
      (≥0.6 BU/mL), as confirmed by central laboratory testing, during the course of the study. The
      secondary endpoints include assessment of incidence of AEs, incidence of SAEs, Annualized
      bleeding rate (ABR) during prophylaxis, Annualized total factor consumption (TFC) in
      international units (IU) and annualized TFC by weight (IU/kg) of moroctocog alfa (AF-CC)
      measured during the up to 8 weeks of treatment, by reason for infusion and total units
      consumed (across all reasons) and number of moroctocog alfa (AF-CC) infusions used to treat
      each bleed.

      This study is a single-country, multicenter, open-label, interventional study which will be
      conducted in India. At least 50 male subjects aged ≥12 years to ≤65 years with moderate or
      severe hemophilia A (FVIII:C ≤5%) who have had at least 50 exposure days (EDs) to
      FVIII-containing products will be enrolled in the study. The overall treatment duration for
      each subject will be up to 8 weeks, with up to a 4-week screening period and a subsequent
      post-treatment 28-day safety observation period. Subjects are requested to continue in the
      study until 24 exposure days (EDs) or a period of up to 8 weeks on moroctocog alfa (AF-CC)
      treatment had occurred (whichever occurs first). Subjects will be treated with a dose and
      regimen of prophylaxis in accordance with the Local Product Development.

      The following subjects will be included in this study:

        1. Male subjects ≥12 years to ≤65 years with a diagnosis of congenital moderate or severe
           hemophilia A (FVIII:C ≤5%).

        2. Documented history of at least 50 exposure days (EDs) to FVIII-containing products.

        3. Evidence of a personally signed and dated informed consent document indicating that the
           subject (or a legally acceptable representative, parent(s)/legal guardian) has been
           informed of all pertinent aspects of the study. For minors under the age of legal
           consent in India, assent of the participating child needs to be documented for the age
           range 12 to 18 in addition to the parental informed consent.

      Subjects presenting with any of the following will not be included in the study:

        1. Prior history of inhibitor to FVIII or positive inhibitor testing (≥0.6 BU/mL) during
           Screening. Clinical signs or symptoms of decreased response to FVIII.

        2. Known hypersensitivity to the active substance or any of the excipients.

        3. Known allergic reaction to hamster proteins.

        4. Presence of any bleeding disorder in addition to hemophilia A.

        5. Participation in other studies involving investigational drug(s) (Phases 1-4) within 30
           days before the current study begins and/or during study participation.

        6. Planned surgery within 6 months from the start of the study.

        7. Unsuitable to participate in study for any other reason as assessed by the investigator;
           including any disorder, except for conditions associated with hemophilia A, which in the
           investigator's opinion might jeopardize subject's safety or compliance with the
           protocol.

        8. Subjects (or a legally acceptable representative) is not able to understand study
           documents and study procedure.

        9. Immunocompromised subjects due to human immunodeficiency virus (HIV) infection (defined
           as viral load above or equal to 100,000 copies/mL; and for HIV+ subjects: cluster of
           differentiation 4 positive (CD4+) lymphocyte count below or equal to 200/μL). HIV status
           and CD4+ lymphocyte count results may be obtained at screening or from available medical
           records; results must be not older than 6 months prior to screening.

       10. Subjects who are investigational site staff members directly involved in the conduct of
           the study and their family members, site staff members otherwise supervised by the
           Investigator, subjects who have been previously enrolled into the study, or subjects who
           are Pfizer employees directly involved in the conduct of the study.

       11. Planned use of any non-study medication for treatment of hemophilia (eg, other factor
           replacement agents, bypassing agents, or non-factor treatments [such as anti-tissue
           factor pathway inhibitors]).

      The investigator will assign subject identification numbers sequentially to the subjects as
      they are screened for the study. This identification number will be retained throughout the
      study. Pfizer will provide the investigators with a sufficient amount of moroctocog alfa
      (AF-CC). Once moroctocog alfa (AF-CC) is dispensed to a subject it must not be re-dispensed
      to another subject. The product should be prepared, reconstituted, and used in accordance
      with procedures provided by their physicians. Moroctocog alfa (AF-CC) will be administered by
      the investigator or a delegate at Visits 2 and 3. For administration between study visits,
      the product will be administered in accordance with procedures provided by their physicians.
      Subjects or caregivers/parents of subjects will be trained on how to administer moroctocog
      alfa (AF-CC) away from the study site, as applicable. Moroctocog alfa (AF-CC) should be
      administered prophylactically in previously treated patients at a dose of 30±5 IU/kg given 3
      times weekly. For on-demand treatment, the amount to be administered and the frequency of
      administration should always be tailored to the clinical effectiveness in individual
      subjects. In the interest of simplifying dosing and minimizing potential waste, a dosing
      variance of ±5 IU/kg is permitted throughout the study.

      The investigator, or an approved representative, eg, study coordinator, will ensure that all
      investigational products, including any comparative agents and/or marketed products are
      stored in a secured area with controlled access under recommended storage conditions and in
      accordance with applicable regulatory requirements. Moroctocog alfa (AF-CC) should be stored
      in its original container and in accordance with the storage conditions stated on the label.
      The reconstituted solution of moroctocog alfa (AF-CC) may be stored at room temperature prior
      to infusion. The reconstituted solution of moroctocog alfa (AF-CC) does not contain
      preservative and should be infused within 3 hours after reconstitution. The investigator's
      site must maintain adequate records documenting the receipt, use, loss, or other disposition
      of the drug supplies. When investigational product is taken home by the subject, any unused
      products must be returned to the investigator by the subject at Visit 4. All used and unused
      vials of moroctocog alfa (AF-CC) and unused diluent syringes will be used for investigational
      product accountability. Administration of moroctocog alfa (AF-CC) by subjects or their
      caregivers away from the study site should be captured in the Subject Infusion Log. The
      monitor will review drug accountability during routine monitoring visits. Drug accountability
      will be done at all study visits after Day 1 until Visit 4. Any discrepancies must be
      investigated and their resolution documented.

      The use of permitted concomitant medication must be in accordance with the study drug label.
      The use of concomitant treatments will be recorded throughout the study.

      Study visits will include screening visit( Visit 1- within 28 Days prior to Day 1), Visit 2
      (Day 1), Visit 3 (Day 24-32), Visit 4(Day 52-60) and End of Study Visit (Day 80-88 or
      earlier) Subjects may withdraw from the study at any time at their own request, or they may
      be withdrawn at any time at the discretion of the investigator. Any subject who uses
      non-study medication for the treatment of hemophilia (eg, other factor replacement agents,
      bypassing agents, or non-factor treatments [such as anti-tissue factor pathway inhibitors])
      will be considered to have a protocol violation and will be withdrawn from the study. The
      exception to this would be for subjects who require non-study treatment for a bleed away from
      the study site. This would be considered a protocol deviation rather than a protocol
      violation that would not require withdrawal from the study. Subjects will be withdrawn from
      the study if their central laboratory result for inhibitor assessment at screening does not
      confirm eligibility per the local laboratory result.

      The safety assessments throughout the study will include collection of AEs, laboratory safety
      testing, vital signs, and physical examination at the time points specified in protocol, but
      can be conducted at other time points at the investigator's discretion. All observed or
      volunteered AEs regardless of suspected causal relationship to the investigational product(s)
      will be reported as described in the protocol. The efficacy assessments include Total Factor
      VIII Consumption and bleeds including, Annualized Bleeding Rate During Prophylaxis, Number of
      Moroctocog alfa (AF-CC) Infusions Used to Treat Each Bleed, Annualized Total Factor
      Consumption of Moroctocog Alfa (AF-CC). All data will be collected in the case report form.
    

Intervention name(s): Moroctocog-alfa (AF-CC)
Intervention type(s): Biological
Intervention description(s): Moroctocog-alfa (AF-CC) is indicated for the control and prevention of hemorrhagic episodes and for routine and surgical prophylaxis in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia).
Other intervention name(s): Xyntha
Intervention MeSH terms: Factor VIII
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment