Evaluate Efficacy and Safety of ADVATE in the Standard Prophylaxis Treatment of Severe or Moderately Severe Hemophilia A

Hemophilia A Clinical Trial

Official title:

Evaluate Efficacy and Safety of ADVATE in the Standard Prophylaxis Treatment of Severe or Moderately Severe Hemophilia A

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02282410
• Other study ID #: 2014-053-01
• Status: Not yet recruiting
• Phase: N/A
• First received: October 29, 2014
• Last updated: October 31, 2014
• Start date: December 2014
• Est. completion date: December 2016

Study information

• Verified date: October 2014
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Rongfu Zhou, Doctor
• Phone: +86 13605142342
• Email: rfzhoucn[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Based on the successful pioneer work of Dr Nilsson and her colleagues in Sweden that started in the late 1950's, prophylaxis is recommend 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.

But after the Recombinant Human Coagulation Factor VIII for injection (ADVATE) Patient Assistance Program(Golden Key) was launched in 24 Apr 2014 in Nanjing China, 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 standard prophylaxis under the conditions of routine practice.

Description:

Hemophilia A is an X-linked recessive, congenital bleeding disorder caused by deficient or defective coagulation factor VIII (FVIII). The absence or severe reduction of FVIII leads to 'spontaneous' bleeding episodes (occurring primarily in joints, muscles, and less commonly, in soft tissues) and to excessive bleeding following trauma or injury. Estimations based on the WFH's annual global surveys indicate that the number of people with hemophilia in the world is approximately 400,000. [1] China accounts for a quarter of about 100,000.

Currently, based on the successful pioneer work of Dr Nilsson and her colleagues in Sweden that started in the late 1950's, prophylaxis is recommend as the standard of care for boys with severe haemophilia by WHO and WFH. [2] The efficacy and safety of prophylaxis in preventing bleeds and arthropathy in patients with hemophilia has been confirmed in well-designed clinical studies.[3,4,5]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) [6] 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. [7] The high consumption of factor and cost present a major barrier to use the standard prophylaxis in many countries particularly in the developing world. [8] Many families are looking forward to standard prophylaxis to reducing bleeding episodes, stop or slow the deterioration of joint disease in their sons with severe hemophilia and thus improving their quality of life (QoL). But in China the majority of boys with severe hemophilia A cannot afford the high costs of standard prophylaxis .They can only pay for on-demand treatment or low-dose prophylaxis. But after the Advate Patient Assistance Program(Golden Key) was launched in 24 Apr 2014 in Nanjing China, 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 standard prophylaxis under the conditions of routine practice.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

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 differentiation antigen 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• 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 2-3 times one week with ADVATE for 1 year.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

References & Publications (8)

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. — View 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. Review. — View 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. — View 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. Review. — View 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. — View Citation

Nilsson IM, Berntorp E, Löfqvist 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annual Bleed Rate (ABR)	Every 3 months, evaluate the joint bleeding episode and any other bleeding episodes. After 1 year later, sum up all the bleeding and get the ABR.	3 months up to 1 year	No
Secondary	incidence of new target joints	Incidence of new target joints.	3 months	No
Secondary	joint health of Pettersson score	Status of joint health by X-ray using Pettersson scale.	1 year	No
Secondary	magnetic resonance imaging scoring of joint	Status of joint health by magnetic resonance imaging scoring system.	6 months	No
Secondary	Hemophilia Joint Health Score (HJHS) of joint	Status of joint health using the Hemophilia Joint Health Score (HJHS)	3 months	No
Secondary	Number of Recombinant Human Coagulation Factor VIII for injection (ADAVTE) units	Number of ADVATE infusions required for bleed cessation and Number of ADAVTE units required for bleed cessation	3 months	No
Secondary	Qol assessment	QoL assessment by The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT)	3 months	No
Secondary	Inhibitor rate	Inhibitor rate monitoring: inhibitor will be tested at entry of study, every 3 months and at end of study.	3 months up to 1 year	No