Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A

NCT01405742 | Terminated Phase 3 Results DMC

• 2 other identifiers: PRO10020178R34HL105870-01A1
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this pilot R34 trial is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis comparing once weekly with thrice-weekly recombinant factor VIII. Efficacy will measured by bleeding frequency, factor usage, joint range of motion, cost, quality-of-life, F.VIII level, and inter-dose hypocoagulability by thrombin generation. Safety will be measured by inhibitor formation and bleeding events unresponsive to up to two rescue doses.

Conditions

Severe Hemophilia A

Keywords

Hemophilia; Prophylaxis; Recombinant factor VIII

Outcome Measures

Primary Outcomes (1)

• Number of Bleeds

  The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant.

  Weeks 26 (first intervention) and 52 (second intervention)

Secondary Outcomes (2)

• Inter-dose Hypocoagulability by Thrombin Generation

  The time frame is 52 weeks per subject.

• F.VIII Activity

  The time frame is 52 weeks per subject.

Study Arms (2)

Arm A

EXPERIMENTAL

The intervention for Arm A is 40 IU/kg recombinant factor VIII (rFVIII) by once-weekly intravenous injection for 26 weeks. Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given thrice-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds.

Drug: rF.VIII

Arm B

EXPERIMENTAL

The intervention for Arm B is 40 IU/kg recombinant factor VIII (rFVIII) by thrice-weekly intravenous injection for 26 weeks. Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given once-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds

Drug: rF.VIII

Interventions

rF.VIII DRUG

40 IU/kg recombinant factor VIII will be given once-weekly or thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 72 hour washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly or once-weekly, respectively, by intravenous injection until week 52, with up to two rescue doses per week for bleeds

Also known as: recombinant factor VIII

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males 18 years or older
• Severe hemophilia A (F.VIII \< 0.01 U/ml)
• At least 150 exposure days to F.VIII products
• No detectable inhibitor
• No history of allergic reaction
• Platelets at least 150,000/ul
• If HIV(+), CD4 at least 200/ul, HIV-VL \<48 copies/ml,and cART compliant
• If HCV(+), no splenomegaly,varices,GI bleed,ascites,edema,encephalopathy
• Willingness to comply with cross-over design, randomization schema
• Willingness to keep a personal diary of bleeding frequency and factor use
• Willingness to make every 3 month visits, coagulation testing at wks 2, 28

You may not qualify if:

• Acquired hemophilia
• Any bleeding disorder other than hemophilia A
• Presence of an inhibitor to factor VIII
• Historic platelet count \< 100,000
• Use of experimental drugs
• Surgery anticipate in the next 52 weeks
• Symptomatic HCV(splenomegaly,varices,GI bleed,ascites,edema,encephalopathy)
• Symptomatic HIV(CD4\<200/ul or HIV VL 48 or more copy/ml,cART noncompliant)
• Life expectancy less than 5 years
• Investigational drug or study within 4 weeks prior to study
• Inability to comply with study requirements

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

Georgetown University

Washington D.C., District of Columbia, 20057-1168, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4206, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213-4306, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235-7749, United States

Location

Puget Sound Blood Center

Seattle, Washington, 98104-1256, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Margaret V. Ragni, MD, MPH
• Organization: University of Pittsburgh

ragni@pitt.edu

412-209-7288

Study Officials

• Margaret V. Ragni, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Laurel Yasko

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: July 29, 2011
• Study Start: July 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 7, 2016
• Results First Posted: September 19, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

US (6)