Efficacy and Cost Effectiveness of Pharmacokinetic Dosing in Haemophilia A

NCT02697370 | Completed Phase 4 DMC

• 1 other identifier: 12/SC/0363
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with severe Haemophilia A need prophylactic factor VIII to reduce their risk of joint and soft tissue bleeds and to prevent or reduce joint damage. It is common practice to give enough factor VIII to maintain the trough level above 1% of normal and this has been supported in retrospective studies. The amount of factor VIII required to maintain this trough level varies markedly between patients because their factor VIII half lives are different. This study will assess the role of regular pharmacokinetic (PK)monitoring and dose adjusted factor VIII to establish whether this is a more cost effective way of giving treatment and whether it is feasible in routine clinical practice. Patients will be treated for 6 months with their standard factor VIII regimen and followed up to establish their bleed frequency. They will then receive pharmacokinetic adjusted factor VIII to maintain a trough above 1.5% for a year and their bleed rate compared to standard treatment. If they have increased break through bleeds their factor VIII will be increased to maintain a trough of 3%.

Conditions

Severe Haemophilia A

Keywords

Haemophilia A prophylaxis pharmacokinetic dosing

Outcome Measures

Primary Outcomes (1)

• The number of clinically significant bleeds in patients taking routine prophylaxis compared to prophylaxis dosed according to individual pharmacokinetics

  Factor VIII dosage tailored treatment based on pharmacokinetics

  18 months

Secondary Outcomes (5)

• Compare the factor VIII usage between the two regimens

  18 months

• Compare the total number of all haemarthroses between the two regimens

  18 months

• Compare the total number of all soft tissue bleeds between the two regimens

  18 months

• Compare the quality of life (EQ5D) between the two regimens

  18 months

• Compare the patients' joint status between the two regimens using the HJHS score.

  18 months

Study Arms (1)

Pharmacokinetic based factor VIII dosage

OTHER

Patient's routine prophylactic factor VIII concentrate infusion will be given in the morning and the exact time (hours and minutes) and dose recorded. There is no wash out so the date, time and dose of the previous 2 prophylactic doses must be accurately known. Samples will be collected that afternoon, the following morning and the following afternoon. Samples can be taken at any convenient time but the exact time must be recorded. Factor VIII levels will be measured and this pharmacokinetic data will be used to calculate the dose of factor VIII (to be infused on alternate days) required to maintain a predicted factor VIII ≥1.5 IU/dL at all times(this will be rounded up to the nearest full 250 IU vial)

Drug: Pharmacokinetic based dosage change

Interventions

Pharmacokinetic based dosage change DRUG

Pharmacokinetic based dosing of factor VIII prophylaxis treatment compared to standard prophylactic regimens based on weight.Prophylaxis is prescribed according to routine clinical practice with prophylaxis prescribed on alternate days to maintain predicted target trough of ≥1.5 IU/dL based on sparse blood sampling and Bayesian pharmacokinetic estimation

Also known as: Factor VIII replacement therapy - non brand specific

Pharmacokinetic based factor VIII dosage

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe haemophilia A (baseline factor VIII \< 1IU/dL)
• Age 18 years and above
• Patients taking any regular prophylactic regimen (defined as regular factor VIII infusions, at least 3 times a week, with the aim minimising haemarthroses and other clinically significant bleeds).
• Low titre inhibitors, past history of an inhibitor, abnormal liver function, drugs that interfere with haemostasis and low CD4 counts are allowed.

You may not qualify if:

• Presence of a target joint on prophylaxis (defined as 3 bleeds into one joint, during a 6 month period,during the last year).
• The occurrence of more than 3 haemarthroses in the last year which required more than 2 infusions to resolve

Sponsors & Collaborators

• Hampshire Hospitals NHS Foundation Trust: lead
• University of Wales Cardiff United Kingdom (UK): collaborator
• Uppsala University: collaborator

Study Sites (1)

Basingstoke & North Hampshire Hospital

Basingstoke, RG24 9NA, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A

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

Study Officials

• Savita Rangarajan, FRCP FRCPath

  Basingstoke & North Hampshire Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2016
• First Posted: March 3, 2016
• Study Start: April 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: February 23, 2018

Record last verified: 2018-02

Locations

GB (1)