Clinical trial NCT02280265: Efficacy and Safety of ADVATE Standard Prophylaxis to Hemophilia A
Official title: Evaluate Efficacy and Safety of ADVATE in the Standard Prophylaxis Treatment of Severe or Moderately Severe Hemophilia A.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hemophilia A
Keywords: hemophilia A
standard prophylaxis
Recombinant Human Coagulation Factor VIII for injection
ADVATE
Pediatric
Lead sponsor: Nanjing Medical University
Sponsor class: OTHER
First posted: 2014-10-31
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: ABR
timeFrame: 3 months
Secondary outcomes:
measure: incidence of new target joints
timeFrame: 3 months
measure: Pettersson score of joint
timeFrame: 3 months
measure: magnetic resonance imaging scoring of joint
timeFrame: 6 months
measure: Hemophilia Joint Health Score (HJHS) of joint
timeFrame: 3 months
measure: Number of ADAVTE units
timeFrame: 3 months
measure: QoL of patients wiht hemophilia
timeFrame: 3 months
measure: Inhibitor rate
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.