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Efficacy and Safety of ADVATE Standard Prophylaxis to Hemophilia A

Primary Purpose

Hemophilia A

Status

Unknown status

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Recombinant Human Coagulation Factor VIII for injection

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring hemophilia A, standard prophylaxis, Recombinant Human Coagulation Factor VIII for injection, ADVATE, Pediatric

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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 Determinant 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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ADVATE

Arm Description

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).

Outcomes

Primary Outcome Measures

ABR

To evaluate the Annual Bleeding rate (ABR) in subjects using standard prophylaxis under the conditions of routine practice.

Secondary Outcome Measures

incidence of new target joints

Incidence of new target joints.

Pettersson score of joint

Status of joint health by X-ray using Pettersson score

magnetic resonance imaging scoring of joint

Status of joint health by magnetic resonance imaging scoring system.

Hemophilia Joint Health Score (HJHS) of joint

Status of joint health using HJHS

Number of ADAVTE units

Number of Recombinant Human Coagulation Factor VIII for injection (ADAVTE) units required for bleed cessation and Number of ADVATE infusions required for bleed cessation

QoL of patients wiht hemophilia

QoL assessment by Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT)

Inhibitor rate

Inhibitor rate monitoring: inhibitor will be tested at entry of study, every 3 months and at end of study.

Full Information

NCT ID

NCT02280265

First Posted

October 28, 2014

Last Updated

October 29, 2014

Sponsor

Nanjing Medical University

1. Study Identification

Unique Protocol Identification Number

NCT02280265

Brief Title

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

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Unknown status

Study Start Date

November 2014 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Nanjing Medical University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia A

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ADVATE

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Recombinant Human Coagulation Factor VIII for injection

Other Intervention Name(s)

ADVATE

Intervention Description

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

Primary Outcome Measure Information:

Title

ABR

Description

To evaluate the Annual Bleeding rate (ABR) in subjects using standard prophylaxis under the conditions of routine practice.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

incidence of new target joints

Description

Incidence of new target joints.

Time Frame

3 months

Title

Pettersson score of joint

Description

Status of joint health by X-ray using Pettersson score

Time Frame

3 months

Title

magnetic resonance imaging scoring of joint

Description

Status of joint health by magnetic resonance imaging scoring system.

Time Frame

6 months

Title

Hemophilia Joint Health Score (HJHS) of joint

Description

Status of joint health using HJHS

Time Frame

3 months

Title

Number of ADAVTE units

Description

Number of Recombinant Human Coagulation Factor VIII for injection (ADAVTE) units required for bleed cessation and Number of ADVATE infusions required for bleed cessation

Time Frame

3 months

Title

QoL of patients wiht hemophilia

Description

QoL assessment by Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT)

Time Frame

3 months

Title

Inhibitor rate

Description

Inhibitor rate monitoring: inhibitor will be tested at entry of study, every 3 months and at end of study.

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject has hemophilia A with FVIII≤2 %. Previously treated patients (PTPs). Age from 2 to 18 years. Exclusion Criteria: 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 Determinant 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

12. IPD Sharing Statement

Citations:

PubMed Identifier

10554828

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.

Results Reference

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PubMed Identifier

8846496

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.

Results Reference

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PubMed Identifier

17687129

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.

Results Reference

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PubMed Identifier

21255253

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.

Results Reference

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PubMed Identifier

22212248

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.

Results Reference

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PubMed Identifier

22776238

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.

Results Reference

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PubMed Identifier

1640190

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.

Results Reference

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PubMed Identifier

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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.

Results Reference

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Efficacy and Safety of ADVATE Standard Prophylaxis to Hemophilia A

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