A clinical trial investigating safety and efficacy of a long-acting factor VIII in children (age <12 years) with severe hemophila A

• Register: EUCTR
• Last refreshed on: 17 May 2016
• Main ID: EUCTR2012-004434-42-ES
• Date of registration: 05/10/2015
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: A clinical trial investigating safety and efficacy of a long-acting factor VIII in children (age <12 years) with severe hemophila A
• Scientific title: A multi-center, phase III, non-controlled, open-label trial to evaluate the pharmacokinetics, safety, and efficacy of BAY 94-9027 for prophylaxis and treatment of bleeding in previously treated children (age <12 years) with severe hemophilia A - PROTECT KIDS
• Date of first enrolment: 24/11/2015
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004434-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Bulgaria, Canada, Dominican Republic, European Union, Greece, Israel, Italy, Lithuania, Netherlands, New Zealand, Poland, Puerto Rico, Spain, United Kingdom, United States

Contacts

• Name: Bayer Clin. Trials Contact CTP Team
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clin. Trials Contact CTP Team
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male, age <12 years to be enrolled in 2 subgroups:
- age 6 to <12 years
- age < 6 years

Subjects in the expansion group are to be <6 years of age.

2. Severe hemophilia A defined as < 1% factor VIII concentration (FVIII:C) by measurement at the time of screening or from reliable prior documentation (eg, measurement in other clinical trials, results from approved clinical laboratory, or diagnostic genetic testing)

3. > 50 ED with any FVIII concentrate(s) (plasma derived or recombinant)

4. Willingness and ability of subjects and/or parents to complete training in the use of the EPD and to document infusions during the study

5. Written informed consent by parent/legal representative. Assent should be sought from subjects, if appropriate
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Current evidence of inhibitor to FVIII measured using the Nijmegen-modified Bethesda assay (>0.6 BU/mL) at the time of screening (central laboratory). Subjects should not have received FVIII within 72 h prior to the collection of screening samples and should have had FVIII administered within the prior 2-3 weeks.

2. History or presence of Factor VIII inhibitors. Inhibitor to FVIII is defined as a titer >0.6 BU/mL or clinical history suggestive of inhibitor requiring modification of treatment. (Subjects with a maximum historical titer of <1.0 BU on no more than 1 occasion with the classical Bethesda assay but at least 3 subsequent negative results [<0.6 BU] are eligible.)

3. Any other inherited or acquired bleeding disorder in addition to hemophilia A

4. Platelet count < 100,000/mm3

5. Creatinine > 2x upper limit of normal

6. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5x upper
limit of normal

7. Known hypersensitivity to the drug substance, or any of its components (eg, mouse or hamster protein)

8. The subject is currently participating in another investigational drug study, or has participated in a clinical study involving an investigational drug within 30 days of study entry. Subjects who are currently participating in an investigational study in which they are treated with a currently marketed FVIII concentrate are not excluded. Subjects currently treated with BAY 81-8973 may continue treatment with the product up to the start of Visit 1.

9. Any individual who is receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids (> 14 days) within the last 3 months.

10. The subject is identified by the investigator as being unable or unwilling to perform study procedures.

11. Previous assignment to treatment during this study.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

severe hemophilia A (<1% FVIII:C)
MedDRA version: 18.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 18.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: BAY 94-9027 (500 IU/vial)
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Damoctocog alfa pegol
Current Sponsor code: BAY 94-9027
Other descriptive name: PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 200-

Product Name: BAY 94-9027 (1000 IU/vial)
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Damoctocog alfa pegol
Current Sponsor code: BAY 94-9027
Other descriptive name: PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 400-

Product Name: BAY 94-9027 (3000 IU/vial)
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Damoctocog alfa pegol
Current Sponsor code: BAY 94-9027
Other descriptive name: PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 1200-

Product Name: BAY 94-9027 (250 IU/vial)
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Damoctocog alfa pegol
Current Sponsor code: BAY 94-9027
Other descriptive name: PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: - Number of bleedings: at the end of treatment visit
- Assessment of PK values: at the PK visit
- Response to treatment of acute bleedings: end of treatment visit

Main Objective: To evaluate pharmacokinetics, safety, and efficacy of BAY 94-9027 for prophylaxis and treatment of bleeding in previously treated patients with hemophilia A

Expansion group (Part 2)
To further evaluate safety of BAY 94-9027 for prophylaxis and treatment of bleeding in PTPs with hemophilia A below 6 years of age.

Primary end point(s): Primary endpoints:
- Number of bleeding events during prophylactic treatment
- Assessment of PK, including Cmax, incremental recovery, MRT, Apparent volume of distribution at steady state (Vss), half-life, area under the curve (AUC), and clearance, in at least 12 subjects in each age subgroup, with at least 4 pre-selected time points between pre-dose and 72 h post-infusion.
- Response of acute bleeding events to treatment will be rated using a 4-point scale (poor, moderate, good, or excellent) by the subject/parent or by the treating physician if the subject is hospitalized

Expansion group (Part 2)
Primary endpoint: Characterization of the potential immune response.

Secondary Objective: Primary endpoints:
- Number of bleeding events during prophylactic treatment
- Assessment of PK, including Cmax, incremental recovery, MRT, Apparent volume of distribution at steady state (Vss), half-life, area under the curve (AUC), and clearance, in at least 12 subjects in each age subgroup, with at least 4 pre-selected time points between pre-dose and 72 h post-infusion.
- Response of acute bleeding events to treatment will be rated using a 4-point scale (poor, moderate, good, or excellent) by the subject/parent or by the treating physician if the subject is hospitalized

Expansion group (Part 2)
Primary endpoint: Characterization of the potential immune response.

Secondary Outcome(s)

Secondary end point(s): - Inhibitor development after 10-15 and 50 ED
- Assess incremental recovery in all subjects
- Safety and tolerability assessments

Timepoint(s) of evaluation of this end point: - Inhibitor development: after 10-15 and after 50 ED of each subject
- Safety and tolerability assessments: at the end of treatment visit and FU visit

Secondary ID(s)

2012-004434-42-GB

BAY94-9027/15912

Source(s) of Monetary Support

Bayer HealthCare AG