Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A

NCT ID: NCT01181128

Last Updated: 2021-01-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

165 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2012-08-31

Brief Summary

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The primary objectives of this study are: to evaluate the safety and tolerability of rFVIIIFc administered as a prophylaxis (Arm 1), weekly (Arm 2), on-demand (Arm 3), and surgical treatment regimen; to evaluate the efficacy of the rFVIIIFc tailored prophylaxis regimen (Arm 1); to evaluate the efficacy of rFVIIIFc administered as an on-demand (Arm 3) and surgical treatment regimen. The secondary objectives of this study are: to characterize the PK profile of rFVIIIFc and compare the PK of rFVIIIFc with the currently marketed product, Advate®; to characterize the range of dose and schedules required to adequately prevent bleeding in a prophylaxis regimen, maintain hemostasis in a surgical setting, or to treat bleeding episodes in an on-demand, weekly treatment, or prophylaxis setting.

Detailed Description

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Participants are assigned to one of three treatment regimens: 1) a tailored prophylaxis regimen, 2) a weekly dosing regimen, or 3) an on-demand regimen. Treatment continued for 28 (±2) to 52 (±2) weeks. PK assessments for all participants are conducted on varying schedules, according to participants' group assignments. Additionally, two subgroups are defined. One subgroup of participants undergo PK profiling with a single dose of the comparator Advate®. A second subgroup consists of participants from any of the treatment arms that required surgery during the study. Depending upon country location, participants might have the option of continuing treatment within study 8HA01EXT (NCT01454739).

Conditions

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Severe Hemophilia A

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Individualized (Tailored) Prophylaxis

On rFVIIIFc Day 0, all participants underwent pharmacokinetic (PK) analysis with 50 IU/kg rFVIIIFc to estimate their PK parameters and guide the appropriate dose or interval of dosing. A subset of participants (Sequential PK subgroup) also had PK analyses performed with a single dose of 50 IU/kg Advate (Advate Day 0) within 8 weeks prior to rFVIIIFc Day 0. A \>= 96 hour washout was performed before the PK dose of Advate or rFVIIIFc was administered. Repeat PK profiling with a single dose of 50 IU/kg rFVIIIFc was conducted at Week 14 or after 12 to 24 weeks of prophylaxis with rFVIIIFc.

After PK assessments, all participants started twice weekly treatment with 25 IU/kg of rFVIIIFc via intravenous (IV) injection on Day 1 and 50 IU/kg on Day 4, followed by individualized dose and interval modification within the range of 25 to 65 IU/kg every 3 to 5 days, as determined by rFVIIIFc PK analysis, to maintain a trough level of 1% to 3% (or higher, as clinically indicated) FVIII activity.

Group Type EXPERIMENTAL

Factor VIII (rFVIIIFc)

Intervention Type DRUG

Advate®

Intervention Type DRUG

Weekly Prophylaxis

65 IU/kg of rFVIIIFc via IV injection every 7 days

Group Type EXPERIMENTAL

Factor VIII (rFVIIIFc)

Intervention Type DRUG

Episodic (On-Demand) Dosing

10 to 50 IU/kg rFVIIIFc via IV injection, as required to treat a bleeding episode

Group Type EXPERIMENTAL

Factor VIII (rFVIIIFc)

Intervention Type DRUG

Interventions

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Factor VIII (rFVIIIFc)

Intervention Type DRUG

Advate®

Intervention Type DRUG

Other Intervention Names

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Recombinant Factor VIII Fc Fusion Protein octocog alfa Antihemophilic Factor [Recombinant] Plasma/Albumin Free Method

Eligibility Criteria

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Inclusion Criteria

* Male, ≥12 years of age with weight at least 40 kg
* Diagnosed with severe hemophilia A, defined as \<1 IU/dL (\<1%) endogenous Factor VIII)
* History of at least 150 documented prior exposure days to any Factor VIII product
* Platelet count ≥100,000 cells/μL

Exclusion Criteria

* History of Factor VIII inhibitors
* Kidney and liver dysfunction
* Diagnosed with other coagulation disorder(s) in addition to hemophilia A
* Prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
Minimum Eligible Age

12 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role collaborator

Bioverativ Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Bioverativ Therapeutics Inc.

Locations

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Little Rock, Arkansas, United States

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Los Angeles, California, United States

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Orange, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Washington D.C., District of Columbia, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Boston, Massachusetts, United States

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East Lansing, Michigan, United States

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Las Vegas, Nevada, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Camperdown, New South Wales, Australia

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Adelaide, South Australia, Australia

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Perth, Western Australia, Australia

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Vienna, , Austria

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Brussels, , Belgium

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Campinas, , Brazil

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Calgary, , Canada

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Toronto, , Canada

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Vancouver, , Canada

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Lyon, , France

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Bonn, Northwest, Germany

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Berlin, State of Berlin, Germany

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Hong Kong, , Hong Kong

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Bangalore, Karna, India

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Pune, Mahara, India

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New Delhi, National Capital Territory of Delhi, India

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Ludhiana, Punjab, India

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Vellore, Tamil Nadu, India

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Ramat Gan, , Israel

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Florence, FI, Italy

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Milan, MI, Italy

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Vicenza, VI, Italy

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Kashihara-shi, , Japan

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Kawasaki-shi, , Japan

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Kitakyushu-shi, , Japan

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Nagoya, , Japan

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Shinjuku-ku, , Japan

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Suginami-ku, , Japan

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Palmerston North, , New Zealand

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Johannesburg Parktown, Gauteng, South Africa

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Cape Town, W Cape, South Africa

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Barcelona, , Spain

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Madrid, , Spain

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Gothenburg, , Sweden

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Zurich, , Switzerland

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Basingstoke, , United Kingdom

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Cambridge, , United Kingdom

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Glasgow, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Countries

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United States Australia Austria Belgium Brazil Canada France Germany Hong Kong India Israel Italy Japan New Zealand South Africa Spain Sweden Switzerland United Kingdom

References

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Mahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, Pabinger I, Hanabusa H, Gupta N, Kulkarni R, Fogarty P, Perry D, Shapiro A, Pasi KJ, Apte S, Nestorov I, Jiang H, Li S, Neelakantan S, Cristiano LM, Goyal J, Sommer JM, Dumont JA, Dodd N, Nugent K, Vigliani G, Luk A, Brennan A, Pierce GF; A-LONG Investigators. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014 Jan 16;123(3):317-25. doi: 10.1182/blood-2013-10-529974. Epub 2013 Nov 13.

Reference Type RESULT
PMID: 24227821 (View on PubMed)

Shapiro AD, Ragni MV, Kulkarni R, Oldenberg J, Srivastava A, Quon DV, Pasi KJ, Hanabusa H, Pabinger I, Mahlangu J, Fogarty P, Lillicrap D, Kulke S, Potts J, Neelakantan S, Nestorov I, Li S, Dumont JA, Jiang H, Brennan A, Pierce GF. Recombinant factor VIII Fc fusion protein: extended-interval dosing maintains low bleeding rates and correlates with von Willebrand factor levels. J Thromb Haemost. 2014 Nov;12(11):1788-800. doi: 10.1111/jth.12723. Epub 2014 Oct 10.

Reference Type RESULT
PMID: 25196897 (View on PubMed)

Raheja P, Kragh N, Bystricka L, Eriksson D, Aroui K, Mezghani M, Barbier S, Linari S. Long-term efmoroctocog alfa prophylaxis improves perceived pain, mental, and physical health in patients with hemophilia A: post hoc analysis of phase III trials using patient-reported outcomes. Ther Adv Hematol. 2024 Jul 30;15:20406207241257917. doi: 10.1177/20406207241257917. eCollection 2024.

Reference Type DERIVED
PMID: 39091324 (View on PubMed)

Katragadda S, Neelakantan S, Diao L, Wong N. Population Pharmacokinetic Analysis of Recombinant Factor VIII Fc Fusion Protein in Subjects With Severe Hemophilia A: Expanded to Include Pediatric Subjects. J Clin Pharmacol. 2021 Jul;61(7):889-900. doi: 10.1002/jcph.1854. Epub 2021 Apr 14.

Reference Type DERIVED
PMID: 33719084 (View on PubMed)

Other Identifiers

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997HA301

Identifier Type: -

Identifier Source: org_study_id

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