A study of safety, effect on the immune system and blood clotting of BAX855 (factor VIII of blood clotting) in pediatric patients who have not received or received minimal treatment for their severe hemophilia A.

• Register: EUCTR
• Last refreshed on: 23 October 2023
• Main ID: EUCTR2015-002136-40-ES
• Date of registration: 15/10/2015
• Prospective Registration: Yes
• Primary sponsor: Baxalta Innovations GmbH
• Public title: A study of safety, effect on the immune system and blood clotting of BAX855 (factor VIII of blood clotting) in pediatric patients who have not received or received minimal treatment for their severe hemophilia A.
• Scientific title: Phase 3, prospective, multi-center, open label study to investigate safety, immunogenicity, and hemostatic efficacy of PEGylated Factor VIII (BAX 855) in previously untreated patients (PUPs) and minimally treated patients (MTPs) < 6 years with severe hemophilia A (FVIII < 1%) - BAX855 PUP study
• Date of first enrolment: 19/11/2015
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002136-40
• 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

Australia, Austria, Belgium, Bulgaria, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Korea, Republic of, Lithuania, Malaysia, Netherlands, New Zealand, Norway, Poland, Romania, Singapore, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Maria Teresa Alvarez Roman
• Affiliation: Maria Teresa Alvarez Roman

• Name: Maria Teresa Alvarez Roman
• Affiliation: Maria Teresa Alvarez Roman

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject is < 6 years old at the time of screening
2. Subject is previously untreated or minimally treated with = 3 EDs to ADVATE or BAX 855 at any time prior to screening
3. Subject has severe hemophilia A (FVIII < 1%) as determined by the central laboratory, or a historical FVIII level < 1% as determined at any local laboratory and/or a FVIII gene mutation consistent with severe hemophilia A
4. Subject is immune competent with a CD4+ count > 200 cells/mm3, as confirmed by central laboratory at screening
5. Parent or legally authorized representative is willing and able to comply with the requirements of the protocol
Additional inclusion criteria for Part B (ITI):
6. Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion
7. Subject has a confirmed inhibitor titer (= 0.6 BU) as determined by the central laboratory based on a second repeat blood sample and requires ITI therapy
Are the trial subjects under 18? yes
Number of subjects for this age range: 110
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. Subject has detectable FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
2. Subject has a history of FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening
3. Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand’s disease)
4. Subject has been previously treated with FFP, cryoprecipitate, any type of FVIII concentrate other than ADVATE or BAX 855v or was administered ADVATE or BAX 855 for > 3 EDs at any time prior to screening
5. Subject has received any kind of blood-transfusion such as PRBC, platelets or plasma prior to screening at any time prior to screening
6. The subject’s weight is < 5 kg
7. Subject’s platelet count is < 100,000/mL
8. Subject has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80
9. Subject has severe chronic hepatic dysfunction [eg, > 5 times upper limit of normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or a documented INR > 1.5] in his medical history or at the time of screening
10. Subject has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal)
11. Subject has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation
12. Subject is scheduled to receive during the course of the study a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral chemotherapy
13. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
14. Parent or legally authorized representative has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
15. Parent, legally authorized representative or subject are a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.
Additional exclusion criteria for Part B (ITI)
16. Spontaneous disappearance of the inhibitor prior to ITI
17. FVIII inhibitor titer = 0.6 BU is not confirmed by a second new blood sample and determined at the central laboratory
18. Inability or unwillingness to comply with the protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Severe hemophilia A (FVIII <1%)
MedDRA version: 18.1 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850

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

Intervention(s)

Product Name: PEGylated rFVIII
Product Code: BAX855
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: Not applicable
Current Sponsor code: BAX855
Other descriptive name: BAX 855 (PEGYLATED RFVIII)
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 250-
INN or Proposed INN: Not applicable
Current Sponsor code: BAX 855
Other descriptive name: BAX 855 (PEGYLATED RFVIII)
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: Not applicable
Current Sponsor code: BAX 855
Other descriptive name: BAX 855 (PEGYLATED RFVIII)
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000-
INN or Proposed INN: Not applicable
Current Sponsor code: BAX 855
Other descriptive name: BAX 855 (PEGYLATED RFVIII)
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 2000-

Primary Outcome(s)

Secondary Objective: Safety
1. To determine the immunogenicity of BAX 855 in terms of binding IgG and IGM antibodies to FVIII, PEG-FVIII and PEG
2. To determine the safety of BAX 855 based on adverse events (AEs) and serious adverse events (SAEs)
Hemostatic Efficacy
3. To assess the efficacy of prophylactic treatment with BAX 855
4. To characterize the efficacy of BAX 855 in the control of bleeding episodes
5. To evaluate the efficacy of BAX 855 for perioperative management, if surgery is required
Pharmacokinetics
6. To determine the incremental recovery (IR) of BAX 855 at baseline and over time
7. To determine half-life of BAX 855 at baseline (optional)

Primary end point(s): Incidence of FVIII inhibitor development
The success rate of ITI therapy with BAX 855

Timepoint(s) of evaluation of this end point: The set of subjects to be analyzed includes all subjects who developed an inhibitor (at any time) and all subjects who did not develop an inhibitor and had = 50 EDs. An interim analysis is planned after 50 subjects have completed 50 EDs. The final CSR will also analyze subjects who develop an inhibitor and subjects who did not, but completed at least 100 EDs.

Main Objective: To determine safety including immunogenicity of BAX 855 based on the
incidence of inhibitor development to FVIII (= 0.6 BU/mL using the Nijmegen modification of the Bethesda assay)

Secondary Outcome(s)

Secondary end point(s): Binding IgG and IgM antibodies to FVIII, PEG-FVIII and PEG
AEs and SAEs
Clinically significant changes in vital signs and clinical laboratory parameters (hematology and clinical chemistry)
Efficacy:
? Annualized bleeding rate (ABR) for prophylactic and on-demand treatment
? Number of BAX 855 infusions per bleeding episode
? Overall hemostatic efficacy rating at 24 h after initiation of treatment and at resolution of bleed
? Weight-adjusted consumption of BAX 855 per month, per year and per event (prophylaxis, treatment of bleeding episode, surgery) and the number of infusions per month and per year
? Assessment of intra-, post- and perioperative hemostatic efficacy in case of surgery
? Intra- and postoperative blood loss in case of surgery
Pharmacokinetics:
? IR at baseline and over time
? Half-life at baseline (optional)
Additional Outcome Measures for ITI:
The rate of partial success and failure of ITI with BAX 855
ABR during ITI
Weight-adjusted consumption of BAX 855 per month and per year for each ITI regimen employed

Timepoint(s) of evaluation of this end point: Binding antibodies to FVIII, BAX 855 and PEG and all other secondary safety outcome measures will be analyzed descriptively.
The ABR will be analyzed by point and interval estimates derived from a negative binomial model with treatment regimen (on-demand vs. prophylaxis) as a covariate and the duration of the observation period as an offset. Other secondary efficacy outcome measures as well as IR over time will be analyzed descriptively.
Outcomes of ITI will be summarized descriptively.

Secondary ID(s)

2015-002136-40-GB

261203

Source(s) of Monetary Support

Baxalta Innovations GmbH

Ethics review

Status: Approved
Approval date: 05/11/2015
Contact: