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

• ClinicalTrials.gov Identifier: NCT02448680
• Recruitment Status: Completed
• First Posted: May 19, 2015
• Results First Posted: August 28, 2020
• Last Update Posted: September 29, 2020
• Sponsor: LFB USA, Inc.
• Collaborator: Laboratoire français de Fractionnement et de Biotechnologies
• Information provided by (Responsible Party): LFB USA, Inc.

Tracking Information

• First Submitted Date: May 15, 2015
• First Posted Date: May 19, 2015
• Results First Submitted Date: July 31, 2020
• Results First Posted Date: August 28, 2020
• Last Update Posted Date: September 29, 2020
• Actual Study Start Date: December 7, 2015
• Actual Primary Completion Date: June 30, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2020)

• Proportion of Successfully Treated Mild/Moderate Bleeding Episodes Per FDA Requirement. [ Time Frame: 12 hours after first administration of study drug ]
  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
• Proportion of Successfully Treated Bleeding Episodes (Mild/Moderate/Severe) Per EMA Definition [ Time Frame: 12 hours after first administration of study drug ]
  • "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.

Original Primary Outcome Measures (submitted: May 18, 2015)

Bleeding episode treatment success [ Time Frame: 12 hours after first administration of study drug ]

No additional hemostatic product required after 12 hours of first dose

Current Secondary Outcome Measures (submitted: August 26, 2020)

• Patient-Reported "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes [ Time Frame: 12 hour after first administration of study drug ]
  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.
• Time to Patient Assessment of a "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes [ Time Frame: Within 24 hours of Bleeding Episode ]
  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.
• Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode [ Time Frame: Within 24 hours of Bleeding Episode ]
  The number of study drug administrations with non-missing dose information in order to treat one mild/moderate bleeding episode.
• Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode [ Time Frame: Within 24 hours of Bleeding Episode ]
  The total amount of study drug administered in order to treat one mild/moderate bleeding episode.

Original Secondary Outcome Measures (submitted: May 18, 2015)

Time to bleeding success [ Time Frame: 12 hours ]

Patients shall rate the treatment of each bleeding episode. If treatment occurs under direct supervision of treating physician, the physician shall rate the response. Ratings based on a four point scale; Excellent, Good, Moderate, None

Current Other Pre-specified Outcome Measures (submitted: September 8, 2020)

Mild/Moderate Bleeding Episodes With Successful Pain Relief [ Time Frame: 12 hour after first administration of study drug ]

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.

Original Other Pre-specified Outcome Measures (submitted: May 18, 2015)

• Immunogenicity assessment [ Time Frame: Pre-dose, 3 weeks post dose and then every 6 weeks until end of study ]
  Based on Coagulation Factor VIIa (Recombinant), binding antibody levels
• Pharmacokinetic profile assessment [ Time Frame: Half of the patients sampling: at 10±2 minutes, 1 and 4 hours (±10 minutes), and the other half of the patients sampling: at 30±5 minutes and 2 and 8 hours (±10 minutes) relative to the start of infusion of study drug ]
  Based on plasma concentrations of Coagulation Factor VIIa (Recombinant)

Descriptive Information

• Brief Title: A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa
• Official Title: 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
• Brief Summary: 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: 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hemophilia A With Inhibitors
• Hemophilia B With Inhibitors

Intervention

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

Study Arms

• Active Comparator: Coagulation Factor VIIa (Recombinant): 75 µg/kg
  75 µg/kg treatment regimen for 3 months
  Intervention: Biological: Coagulation FVIIa (Recombinant)
• Active Comparator: Coagulation Factor VIIa (Recombinant): 225 µg/kg
  225 µg/kg treatment regimen for 3 months
  Intervention: Biological: Coagulation FVIIa (Recombinant)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2020): 25
• Original Estimated Enrollment (submitted: May 18, 2015): 24
• Actual Study Completion Date: August 30, 2017
• Actual Primary Completion Date: June 30, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: up to 11 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States, Bulgaria, Czechia, Georgia, South Africa, Ukraine
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02448680
• Other Study ID Numbers: LFB-FVIIa-007-14
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: LFB USA, Inc.
• Study Sponsor: LFB USA, Inc.
• Collaborators: Laboratoire français de Fractionnement et de Biotechnologies

Investigators

• Principal Investigator: Michael Wang, MD; University of Colorado, Denver

• PRS Account: LFB USA, Inc.
• Verification Date: September 2020