A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or IX in 12 patients ( birth to <6 years old), and 12 patients (≥6 years old to <12 years old).

Detailed Description
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A Phase III Study on the Safety, Pharmacokinetics, and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Pediatric Patients from birth to <12 years old with Inhibitors to Factor VIII or IX: PerSept 2

Official Title
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A Phase III Study on the Safety, Pharmacokinetics, and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Pediatric Patients From Birth to <12 Years Old With Inhibitors to Factor VIII or IX: PerSept 2

Conditions
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Hemophilia A With Inhibitors, Hemophilia B With Inhibitors

Intervention / Treatment
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* Biological: Coagulation FVIIa (Recombinant)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: be male with a diagnosis of congenital hemophilia A or B of any severity have one of the following: a positive inhibitor test BU ≥5, OR a Bethesda Unit (BU) <5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the patient's medical history, precluding the use of factor VIII or IX products to treat bleeding episodes, OR a BU <5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the patient's medical history, precluding the use of factor VIII or IX products to treat bleeding episodes be aged from birth to <12 years old have experienced at least 3 bleeding episodes of any severity in the past 6 months parents or legal guardians must be capable of understanding and be willing to comply with the conditions of the protocol parents or legal guardians must have read, understood, and provided written informed consent Exclusion Criteria: have any coagulation disorder other than hemophilia A or B be immunosuppressed (i.e., the patient may not be receiving systemic immunosuppressive medication; cluster of differentiation 4 (CD4) counts at screening must be >200/µL) have a known allergy or hypersensitivity to rabbits have platelet count <100,000/mL have had a major surgical procedure (e.g. orthopedic, abdominal) within 1 month prior to first administration of study drug have received an investigational drug within 30 days of first study drug administration, or be expected to receive such drug during participation in this study

Ages Eligible for Study
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Maximum Age: 11 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Coagulation Factor VIIa (Recombinant): 75 µg/kg<br>75 µg/kg treatment regimen for 3 months | Biological: Coagulation FVIIa (Recombinant)<br>* A cross over design to assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX<br>|
| Active Comparator: Coagulation Factor VIIa (Recombinant): 225 µg/kg<br>225 µg/kg treatment regimen for 3 months | Biological: Coagulation FVIIa (Recombinant)<br>* A cross over design to assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Successfully Treated Mild/Moderate Bleeding Episodes Per FDA Requirement. | For the primary efficacy endpoint, successful treatment of mild/moderate bleeding episode was defined as meeting all of the following: Good or excellent response noted by the patient/parent/legal guardian or other caregiver, depending on patient's age and maturity Study drug treatment: No further treatment with LR769 beyond timepoint where a good or excellent response for this bleeding episode was noted No other hemostatic treatment needed for this bleeding episode No administration of blood products that would indicate continuation of bleeding beyond timepoint where a good or excellent response for this bleeding episode was noted No increase of pain beyond timepoint where a good or excellent response for this bleeding episode was noted that could not be explained other than as continuation of bleeding | 12 hours after first administration of study drug | 
| Proportion of Successfully Treated Bleeding Episodes (Mild/Moderate/Severe) Per EMA Definition | Good or excellent response noted by the patient/caregiver for mild/moderate bleeding episodes; Good or excellent response noted by the physician for severe bleeding episodes. | 12 hours after first administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-Reported Good or Excellent Response for Mild/Moderate Bleeding Episodes | Based on Patient-Reported Good or Excellent responses as per the below descriptions: Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug. Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage). No additional infusion of study drug was required. | 12 hour after first administration of study drug | 
| Time to Patient Assessment of a Good or Excellent Response for Mild/Moderate Bleeding Episodes | Categories of Response to Treatment are Described as Follows: None: No noticeable effect of the treatment on the bleed or worsening of patient's condition. Continuation of treatment with the study drug was needed. Moderate: Some effect of the treatment on the bleed was noticed, e.g., pain decreased or bleeding signs improved, but bleed continued and required continued treatment with the study drug. Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug. Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required. | Within 24 hours of Bleeding Episode | 
| Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode | The number of study drug administrations with non-missing dose information in order to treat one mild/moderate bleeding episode. | Within 24 hours of Bleeding Episode | 
| Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode | The total amount of study drug administered in order to treat one mild/moderate bleeding episode. | Within 24 hours of Bleeding Episode |