BAY79-4980 Compared to rFVIII-FS in Previously Treated Patients With Severe Hemophilia A

NCT00623727 | Terminated Phase 2 Results DMC

• 2 other identifiers: 127812007-003718-32
• Study Type: interventional
• Target: 143
• Locations: 24 countries
• Sites: 87

Brief Summary

A study to assess treatment with a new formulation of recombinant factor VIII reconstituted with liposomes (BAY79-4980) to evaluate whether a once-a-week treatment is safe and can prevent bleeds in subjects with severe haemophilia A.

Conditions

Hemophilia A

Keywords

Hemophilia A; FVIII disease; rFVIII

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Less Than 9 Total Bleeds Per Year

  Bleeds occurring on the same day were counted as one bleeding event. Bleeds occurring within 72 hours into the same location were also counted as one bleeding event.

  up to one year

Secondary Outcomes (2)

• Percentage of Participants With Less Than 5 Joint Bleeds Per Year

  up to one year

• Number of Joint Bleeds Per Participant Per Year in Responders

  up to one year

Other Outcomes (4)

• Number of Bleeds Per Year

  up to one year

• Percentage of Bleeds Treated by Various Numbers of Injections

  up to one year

• Total rFVIII Consumption Per Year

  up to one year

Study Arms (2)

rFVIII-FS/pegylated liposomes (BAY79-4980)

EXPERIMENTAL

35 IU/kg body weight of BAY79-4980 1x/week plus 2 dummy injections/week (dummy = rFVIII (recombinant factor VIII)-FS (formulated with sucrose) excipient reconstituted in WFI (sterile water for injection))

Biological: rFVIII-FS/pegylated liposomes (BAY79-4980)

rFVIII-FS/WFI (BAY14-2222)

ACTIVE COMPARATOR

25 IU/kg body weight of rFVIII-FS 3x/week (employing 1 percent POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-alone liposome (rFVIII-FS-POPC) as blinding agent used for first weekly injection and rFVIII-FS in WFI for 2nd and 3rd injection)

Biological: rFVIII-FS/WFI (BAY14-2222)

Interventions

rFVIII-FS/pegylated liposomes (BAY79-4980) BIOLOGICAL

35 IU/kg body weight intravenous 1x/week for 52 weeks This arm will be stopped by 30.04.10 the subjects will be offered to change to the active comparator arm

rFVIII-FS/pegylated liposomes (BAY79-4980)

rFVIII-FS/WFI (BAY14-2222) BIOLOGICAL

25 IU/kg body weight intravenous 3x/week for 52 weeks

rFVIII-FS/WFI (BAY14-2222)

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged 12 to 70 years
• Subjects with severe hemophilia A (\< 1% factor VIII \[FVIII\]:C)
• Subjects with equal or greater than 150 exposure days (EDs) with any FVIII in total
• Subjects who have been on-demand treatment with a minimum of 1 relevant bleed per month or have been on secondary prophylaxis treatment with not more than a 3x/week schedule
• Subjects with bleeding events and/or treatments during the last 6 months prior to study entry which are documented in the subjects medical records
• Subjects with no measurable inhibitor activity
• Subjects with no history of FVIII inhibitor antibody formation
• Written informed consent by subject and parent / legal representative, if \< 18 years

You may not qualify if:

• Subjects who are receiving primary prophylaxis
• Subjects on prophylaxis with documented requirements of \> 75 IU/kg/week
• Subjects with any other bleeding disease beside hemophilia A (i.e., von Willebrand disease)
• Subjects with abnormal renal function
• Subjects with elevated hepatic transaminases
• Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study
• Subjects with known hypersensitivity to the active substance, mouse or hamster protein, liposomes or polyethyleneglycol (PEG)
• Subjects who require any pre-medication for FVIII injections

Sponsors & Collaborators

• Bayer: lead

Study Sites (95)

Unknown Facility

Orange, California, 92868, United States

Location

Unknown Facility

Sacramento, California, 95817, United States

Location

Unknown Facility

San Francisco, California, 94143-0324, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

New Orleans, Louisiana, 70112-2699, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

Detroit, Michigan, 48202, United States

Location

Unknown Facility

East Lansing, Michigan, 48823, United States

Location

Unknown Facility

Rochester, Minnesota, 55905, United States

Location

Unknown Facility

Kansas City, Missouri, 64108-9898, United States

Location

Unknown Facility

Las Vegas, Nevada, 89109-2803, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87131-0001, United States

Location

Unknown Facility

Buffalo, New York, 14215, United States

Location

Unknown Facility

Rochester, New York, 14621, United States

Location

Unknown Facility

Winston-Salem, North Carolina, 27157-1009, United States

Location

Unknown Facility

Cincinnati, Ohio, 45229, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104-0506, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15213, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Milwaukee, Wisconsin, 53226, United States

Location

Unknown Facility

Buenos Aires, Ciudad Auton. de Buenos Aires, C1221ADC, Argentina

Location

Unknown Facility

Buenos Aires, Ciudad Auton. de Buenos Aires, C1425AUM, Argentina

Location

Unknown Facility

Rosario, Santa Fe Province, S2000CKF, Argentina

Location

Unknown Facility

Perth, Western Australia, 6000, Australia

Location

Unknown Facility

Vienna, Vienna, 1090, Austria

Location

Unknown Facility

Graz, 8036, Austria

Location

Unknown Facility

Bruxelles - Brussel, 1020, Belgium

Location

Unknown Facility

Bruxelles - Brussel, 1200, Belgium

Location

Unknown Facility

Leuven, 3000, Belgium

Location

Unknown Facility

Calgary, Alberta, T2N 2T9, Canada

Location

Unknown Facility

Edmonton, Alberta, T6G 2C8, Canada

Location

Unknown Facility

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Unknown Facility

Hamilton, Ontario, L8S 4J9, Canada

Location

Unknown Facility

Ottawa, Ontario, K1H 8L6, Canada

Location

Unknown Facility

Toronto, Ontario, M5B 1W8, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 1X8, Canada

Location

Unknown Facility

Santiago, Chile

Location

Unknown Facility

Zagreb, 10000, Croatia

Location

Unknown Facility

Århus N, 8200, Denmark

Location

Unknown Facility

Tallinn, 13419, Estonia

Location

Unknown Facility

Besançon, 25030, France

Location

Unknown Facility

Le Kremlin-Bicêtre, 94275, France

Location

Unknown Facility

Lyon, 69437, France

Location

Unknown Facility

Marseille, 13005, France

Location

Unknown Facility

Montpellier, 34059, France

Location

Unknown Facility

Paris, 75015, France

Location

Unknown Facility

Paris, 75674, France

Location

Unknown Facility

Rennes, 35033, France

Location

Unknown Facility

Strasbourg, 67091, France

Location

Unknown Facility

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Unknown Facility

Münster, North Rhine-Westphalia, 48143, Germany

Location

Unknown Facility

Berlin, State of Berlin, 10249, Germany

Location

Unknown Facility

Tel Litwinsky, 52621, Israel

Location

Unknown Facility

Catania, 95124, Italy

Location

Unknown Facility

Florence, 50134, Italy

Location

Unknown Facility

Milan, 20122, Italy

Location

Unknown Facility

Napoli, 80131, Italy

Location

Unknown Facility

Napoli, 80144, Italy

Location

Unknown Facility

Torino, 10126, Italy

Location

Unknown Facility

Klaipėda, 50809, Lithuania

Location

Unknown Facility

Vilnius, 08661, Lithuania

Location

Unknown Facility

Groningen, 9713 GZ, Netherlands

Location

Unknown Facility

Nijmegen, 6525 GA, Netherlands

Location

Unknown Facility

Utrecht, 3508 GA, Netherlands

Location

Unknown Facility

Auckland, 1023, New Zealand

Location

Unknown Facility

Christchurch, 8001, New Zealand

Location

Unknown Facility

Oslo, 0027, Norway

Location

Unknown Facility

Gdansk, 80-952, Poland

Location

Unknown Facility

Krakow, 31-501, Poland

Location

Unknown Facility

Lodz, 93-510, Poland

Location

Unknown Facility

Poznan, 61-833, Poland

Location

Unknown Facility

Warsaw, 02-776, Poland

Location

Unknown Facility

Timișoara, Timiș County, 300011, Romania

Location

Unknown Facility

Brasov, 50035, Romania

Location

Unknown Facility

Bucharest, 022328, Romania

Location

Unknown Facility

Johannesburg, Gauteng, 2132, South Africa

Location

Unknown Facility

Seville, Andalusia, 41013, Spain

Location

Unknown Facility

Barcelona, Barcelona, 08035, Spain

Location

Unknown Facility

Madrid, Madrid, 28046, Spain

Location

Unknown Facility

Oviedo, Principality of Asturias, 33006, Spain

Location

Unknown Facility

Santa Cruz de Tenerife, Santa Cruz de Tenerife, 38009, Spain

Location

Unknown Facility

Valencia, Valencia, 46026, Spain

Location

Unknown Facility

Bern, 3010, Switzerland

Location

Unknown Facility

Changhua, 500, Taiwan

Location

Unknown Facility

Taipei, 10002, Taiwan

Location

Unknown Facility

Taipei, 11217, Taiwan

Location

Unknown Facility

Adana, 01-330, Turkey (Türkiye)

Location

Unknown Facility

Antalya, 07059, Turkey (Türkiye)

Location

Unknown Facility

Izmir, 35-100, Turkey (Türkiye)

Location

Unknown Facility

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Unknown Facility

London, London, SE1 7EH, United Kingdom

Location

Unknown Facility

Manchester, Manchester, M13 9WL, United Kingdom

Location

Unknown Facility

Cardiff, South Glamorgan, CF14 4XW, United Kingdom

Location

Unknown Facility

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Unknown Facility

Birmingham, B15 2TH, United Kingdom

Location

Related Publications (2)

• Di Minno G, Cerbone AM, Coppola A, Cimino E, Di Capua M, Pamparana F, Tufano A, Di Minno MN. Longer-acting factor VIII to overcome limitations in haemophilia management: the PEGylated liposomes formulation issue. Haemophilia. 2010 Jan;16 Suppl 1:2-6. doi: 10.1111/j.1365-2516.2009.02155.x.

  PMID: 20059562 RESULT

• Powell J, Martinowitz U, Windyga J, Di Minno G, Hellmann A, Pabinger I, Maas Enriquez M, Schwartz L, Ingerslev J; LipLong Study Investigators. Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study. Thromb Haemost. 2012 Nov;108(5):913-22. doi: 10.1160/TH12-03-0188. Epub 2012 Sep 26.

  PMID: 23014711 RESULT

MeSH Terms

Conditions

Hemophilia A

Interventions

BAY 14-2222

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

Limitations and Caveats

The recruitment and double-blind study phase were prematurely terminated after a scheduled interim analysis confirmed overt failure regarding the primary endpoint as judged by the independent Data and Safety Monitoring Board.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 9, 2008
• First Posted: February 26, 2008
• Study Start: June 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: October 1, 2010
• Last Updated: July 15, 2013
• Results First Posted: August 17, 2011

Record last verified: 2013-07

Locations

ES (1); AU (1); CR (1); PL (5); TW (3); DE (3); AR (3); CH (1); BE (3); NZ (2); TU (3); CL (1); GB (6); IT (6); CA (7); NO (1); FR (9); RO (3); LI (2); DK (1); US (20); IL (1); ZA (1); NL (3)