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

NCT02282410 | Unknown DMC

• 1 other identifier: 2014-053-01
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Hemophilia A

Keywords

severe hemophilia A; moderately severe hemophilia A; Recombinant Human Coagulation Factor VIII; standard prophylaxis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• incidence of new target joints

  3 months

• joint health of Pettersson score

  1 year

• magnetic resonance imaging scoring of joint

  6 months

• Hemophilia Joint Health Score (HJHS) of joint

  3 months

• Number of Recombinant Human Coagulation Factor VIII for injection (ADAVTE) units

  3 months

Study Arms (1)

ADVATE standard prophylaxis

EXPERIMENTAL

This study is a prospective, open-label, interventional, multicenter study in a total of 15 PTPs with hemophilia A (FVIII≤2 %).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. 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).

Drug: ADVATE

Interventions

ADVATE DRUG

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.

Also known as: Recombinant Human Coagulation Factor VIII for injection

ADVATE standard prophylaxis

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject has hemophilia A with FVIII≤2 %.
• Previously treated patients (PTPs).
• Age from 2 to 18 years.

You may not qualify if:

• Subject has known hypersensitivity to the active substance or any of the excipients.
• Subject has known allergic reaction to mouse or hamster proteins.
• 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.
• Subject is planned, or likely to have surgery during the study period.
• Subject has end-stage renal failure or evidence of a severe or uncontrolled systemic disease as judged by the investigator.
• Subject has full-blown Acquired Immuno Deficiency Syndrome (AIDS),determined by cluster differentiation antigen 4+ (CD4+) and clinical presentation.
• Subject has active hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels \> 5 times the upper limit of normal).
• 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.
• The subject in the opinion of the investigator is unable or unwilling to comply with study protocol
• Subject is a family member of the investigator or site staff

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Related 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. doi: 10.1046/j.1365-2141.1999.01463.x.

  PMID: 10554828 BACKGROUND

• 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.

  PMID: 8846496 BACKGROUND

• 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.

  PMID: 17687129 BACKGROUND

• 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.

  PMID: 21255253 BACKGROUND

• 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.

  PMID: 22212248 BACKGROUND

• 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.

  PMID: 22776238 BACKGROUND

• 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.

  PMID: 1640190 BACKGROUND

• 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.

  PMID: 19775786 BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; Injections

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

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Ouyang Jian, Doctor

  The Affiliated Nanjing Drum Tower Hospital Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rongfu Zhou, Doctor

CONTACT

+86 13605142342; rfzhoucn@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology-Oncology Department

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: November 4, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 4, 2014

Record last verified: 2014-10