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

Hemophilia A With Inhibitors Clinical Trial

— PERSEPT2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02448680
• Other study ID #: LFB-FVIIa-007-14
• Status: Completed
• Phase: Phase 3
• Start date: December 7, 2015
• Est. completion date: August 30, 2017

Study information

• Verified date: February 2022
• Source: Laboratoire français de Fractionnement et de Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: August 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitors
• Hemophilia B
• 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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Laboratoire français de Fractionnement et de Biotechnologies	LFB USA, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Georgia,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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