BAX 855 Continuation

Baxalta

Status and phase: Completed; Phase 3

Conditions: Hemophilia A

Treatments: Biological: BAX855

Study type: Interventional

Funder types: Industry

Identifiers

NCT01945593

2013-002236-24 (EudraCT Number)

261302

Details and patient eligibility

About

To continue the evaluation of the safety and efficacy of BAX 855 for prophylaxis and treatment of bleeding episodes in adult and pediatric previously treated patients (PTPs) aged ≤ 75 years of age with severe hemophilia A.

Enrollment: 218 patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies can be provided with the continuation study informed consent form (ICF) prior to the end of study visit to review and consider participation in this continuation study. These participants will complete any additional screening assessments within 2 weeks of the previous study's end of study visit and will return to the study site within 6 (± 1) weeks of the previous study end of study visit to confirm eligibility for this continuation study.

• Participants transitioning from other BAX 855 studies who meet ALL of the following criteria are eligible for this study:

  1. Participant has completed a previous BAX 855 study and is willing to immediately transition into this continuation study.
  2. Participant is ≤75 years of age at screening of the previous BAX 855 study.
  3. Participant continues to have a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
  4. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
  5. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
  6. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
  7. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.

• BAX 855 Naïve Participants:

BAX 855 naïve participants who are ≥ 12 years of age can only be enrolled in this continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX 855 naïve participants who are < 12 years of age can only be enrolled in this continuation study after enrollment in the pediatric previously treated patient (PTP) study is closed.

• Enrolment of BAX 855 naïve participants will only start once the sponsor has notified the study sites accordingly.

BAX 855 naïve participants who meet ALL of the following criteria are eligible for this study:

1. Participant is ≤75 years of age at screening.
2. Participant is naïve to BAX 855.
3. Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period.
4. Participant aged ≥ 6 years has documented previous treatment with plasma-derived FVIII or rFVIII for ≥ 150 exposure days (EDs).
5. Participant aged < 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 50 EDs.
6. Participant is currently receiving prophylaxis or on-demand therapy with FVIII.
7. Participant has a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
8. Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
9. Participant is HCV- by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
10. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
11. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.

EXCLUSION CRITERA

• Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies who meet ANY of the following criteria are not eligible for this study:

1. Participant had detectable factor VIII (FVIII) inhibitory antibodies (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.

2. Participant has developed FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at central laboratory in a previous BAX 855 study).

3. Participant has acquired a hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease) in a previous BAX 855 study.

4. Participant has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of normal alanine aminotransferase [ALT], as confirmed by central laboratory at screening).

5. Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.

6. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.

7. Participant is scheduled to use other PEGylated drugs during study participation.

8. Participant is planning to take part in any other clinical study during the course of the continuation study, with the exception of any other parallel BAX 855 study.

9. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.

10. Participant is a family member or employee of the investigator.

    • BAX 855 Naïve Participants:

BAX 855 naïve participants who meet ANY of the following criteria are not eligible for this study:

1. Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
2. Participant has 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. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
4. Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80.
5. Participant has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of normal ALT, as confirmed by central laboratory at screening).
6. Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
7. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
8. Participant has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or scheduled use of such drugs during study participation.
9. Participant has participated in another clinical study involving an IP other than BAX 855 or device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study.
10. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
11. Participant is a family member or employee of the investigator.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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218 participants in 2 patient groups

Fixed BAX855 prophylaxis

Experimental group

Description:

45-80 IU/kg twice weekly to once per week.

Treatment:

Biological: BAX855

Pharmacokinetic (PK)-tailored BAX 855 prophylaxis

Experimental group

Description:

PK-tailored prophylactic BAX855 regimen based on participant's individual PK profile to maintain a Factor VIII (FVIII) trough level

Treatment:

Biological: BAX855