A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (PERSEPT2)

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

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).

Study Overview

• Status: Completed
• Conditions: Hemophilia A With Inhibitors; Hemophilia B With Inhibitors
• Intervention / Treatment: Biological: Coagulation FVIIa (Recombinant)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • University Multiprofile Hospital for Active Treatment "Sveti Georgi"
• Czechia
  • Prague, Czechia
    • University Hospital Motol
• Georgia
  • Tbilisi, Georgia
    • Hematology of Department Hemophilia and Thromboses center
• South Africa
  • Benoni, South Africa
    • Worthwhile Clinical Trials
• Ukraine
  • Kyiv, Ukraine
    • National Specialized Children's Hospital OKHMATDYT, Centre for Hemostatic Pathology (Ukraine)
  • Lviv, Ukraine
    • Institute of blood pathology and transfusion medicine
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Hemophilia & Thrombosis Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Jimmy Everest Center for Cancer and Bleeding Disorders
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center at Dallas / Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Coagulation Factor VIIa (Recombinant): 75 µg/kg; 75 µg/kg treatment regimen for 3 months	Biological: Coagulation FVIIa (Recombinant); 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
Active Comparator: Coagulation Factor VIIa (Recombinant): 225 µg/kg; 225 µg/kg treatment regimen for 3 months	Biological: Coagulation FVIIa (Recombinant); 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mild/Moderate Bleeding Episodes With Successful Pain Relief	Successful pain relief was defined as a Visual Analogue Scale (VAS: 0-100; 0: no pain at all; 100: the worst pain ever possible) pain score at 12 hours after initial study drug administration that was less than the pain score at the start of treatment with study drug.	12 hour after first administration of study drug

Collaborators and Investigators

• Sponsor: Laboratoire français de Fractionnement et de Biotechnologies
• Collaborators: LFB USA, Inc.
• Investigators: Principal Investigator: Michael Wang, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2015
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): August 30, 2017

Study Registration Dates

• First Submitted: May 15, 2015
• First Submitted That Met QC Criteria: May 18, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: LFB-FVIIa-007-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No