Efficacy and Safety of ADVATE Standard Prophylaxis to Hemophilia A

NCT ID: NCT02280265

Last Updated: 2014-10-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2016-12-31

Brief Summary

Hemophilia A is an X-linked recessive, congenital bleeding disorder caused by deficient or defective coagulation factor VIII (FVIII). Prophylaxis is recommended as the standard of care for boys with severe haemophilia by WHO and World Federation Of Hemophilia (WFH). The efficacy and safety of prophylaxis in preventing bleeds and arthropathy in patients with hemophilia has been confirmed in well-designed clinical studies.To keep the factor level above 1%, the standard dosage for patients with severe hemophilia A is 20-40 Units /kg/infusion (average 30 Units /kg) every other day or three times a week. This dosage has a very high consumption of factor, up to 5000-6000 international unit (IU)/kg/year. The high consumption of factor and cost present a major barrier to use the standard prophylaxis in many countries particularly in the developing world.

In China the majority of boys with severe hemophilia A can only pay for on-demand treatment or low-dose prophylaxis. Ao after the affordability of patients was solved and many patients will get more chance to receive standard prophylaxis.

This study is designed to evaluate the Annual Bleeding rate (ABR), joint health outcomes and QoL outcomes in subjects using ADVATE(Recombinant Human Coagulation Factor VIII for injection) standard prophylaxis under the conditions of routine practice.

Conditions

Hemophilia A

Keywords

hemophilia A; standard prophylaxis; Recombinant Human Coagulation Factor VIII for injection; ADVATE; Pediatric

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ADVATE

The baseline ABR will be assessed from bleeding log and clinic records from preceding year. Subjects will initially be treated standard prophylaxis(20 - 40 IU/Kg body weight every 48 ± 6 hours) with Recombinant Human Coagulation Factor VIII for injection(ADVATE) for 1 year. Subjects must be prescribed ADVATE by the treating physician. Data will be collected over a period of 2 years from the time of study enrollment. Study visits are to coincide with routinely rescheduled and emergency visits. Available data from these visits shall be transcribed onto the case report forms (CRFs).

Group Type: EXPERIMENTAL

Recombinant Human Coagulation Factor VIII for injection

Intervention Type: DRUG

Subjects will initially be treated standard prophylaxis(20 - 40 IU/Kg body weight 2 times one week) with ADVATE for 1 year.

Interventions

Recombinant Human Coagulation Factor VIII for injection

Subjects will initially be treated standard prophylaxis(20 - 40 IU/Kg body weight 2 times one week) with ADVATE for 1 year.

Intervention Type: DRUG

Other Intervention Names

ADVATE

Eligibility Criteria

Inclusion Criteria

1. Subject has hemophilia A with FVIII≤2 %.

2. Previously treated patients (PTPs).

3. Age from 2 to 18 years.

Exclusion Criteria

1. Subject has known hypersensitivity to the active substance or any of the excipients.

2. Subject has known allergic reaction to mouse or hamster proteins.

3. Subject has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving another FVIII concentrate or device during the course of this study.

4. Subject is planned, or likely to have surgery during the study period.

5. Subject has end-stage renal failure or evidence of a severe or uncontrolled systemic disease as judged by the investigator.

6. Subject has full-blown Acquired Immuno Deficiency Syndrome (AIDS),determined by Cluster Determinant 4+(CD4+) and clinical presentation.

7. Subject has active hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 5 times the upper limit of normal).

8. Subject has clinical or laboratory evidence of severe liver impairment including (but not limited to) a recent and persistent international normalized ratio (INR)> 1.4, and/or the presence of splenomegaly and/or significant spider angioma on physical exam, and/or a history of esophageal hemorrhage or documented esophageal varices.

9. The subject in the opinion of the investigator is unable or unwilling to comply with study protocol

10. Subject is a family member of the investigator or site staff

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Yongjun Fang,MD

Director of Department of Hematology/Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

Astermark J, Petrini P, Tengborn L, Schulman S, Ljung R, Berntorp E. Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized. Br J Haematol. 1999 Jun;105(4):1109-13. doi: 10.1046/j.1365-2141.1999.01463.x.

Reference Type: BACKGROUND

PMID: 10554828 (View on PubMed)

Berntorp E, Boulyjenkov V, Brettler D, Chandy M, Jones P, Lee C, Lusher J, Mannucci P, Peak I, Rickard K, et al. Modern treatment of haemophilia. Bull World Health Organ. 1995;73(5):691-701.

Reference Type: BACKGROUND

PMID: 8846496 (View on PubMed)

Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, Cohen A, Mathew P, Matsunaga A, Medeiros D, Nugent D, Thomas GA, Thompson AA, McRedmond K, Soucie JM, Austin H, Evatt BL. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007 Aug 9;357(6):535-44. doi: 10.1056/NEJMoa067659.

Reference Type: BACKGROUND

PMID: 17687129 (View on PubMed)

Gringeri A, Lundin B, von Mackensen S, Mantovani L, Mannucci PM; ESPRIT Study Group. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J Thromb Haemost. 2011 Apr;9(4):700-10. doi: 10.1111/j.1538-7836.2011.04214.x.

Reference Type: BACKGROUND

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Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, Patrone L, Wong WY; Prophylaxis Study Group. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012 Mar;10(3):359-67. doi: 10.1111/j.1538-7836.2011.04611.x.

Reference Type: BACKGROUND

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Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013 Jan;19(1):e1-47. doi: 10.1111/j.1365-2516.2012.02909.x. Epub 2012 Jul 6.

Reference Type: BACKGROUND

PMID: 22776238 (View on PubMed)

Nilsson IM, Berntorp E, Lofqvist T, Pettersson H. Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med. 1992 Jul;232(1):25-32. doi: 10.1111/j.1365-2796.1992.tb00546.x.

Reference Type: BACKGROUND

PMID: 1640190 (View on PubMed)

Ljung R. Prophylactic therapy in haemophilia. Blood Rev. 2009 Nov;23(6):267-74. doi: 10.1016/j.blre.2009.08.001. Epub 2009 Sep 22.

Reference Type: BACKGROUND

PMID: 19775786 (View on PubMed)

Other Identifiers

Prophylaxis201407008-1

Identifier Type: -

Identifier Source: org_study_id