BAX 855 Continuation
- Conditions
- Hemophilia A
- Registration Number
- NCT01945593
- Lead Sponsor
- Baxalta now part of Shire
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 218
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Annualized Bleed Rate (ABR) - Spontaneous Bleeds Baseline through end of study (53 months) The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. The ABR of spontaneous bleeds was reported separately for twice weekly, PK-t R, each of the every 5 days and every 7 days treatment regimens at the time of bleed.
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII) Baseline through end of study (53 months) Inhibitory antibodies to Factor VIII were measured by the Nijmegen modification of the Bethesda assay. Inhibitors had to be confirmed by 2 separate assessments within a 2 to 4 week period from the central laboratory.
- Secondary Outcome Measures
Name Time Method Total Annualized Bleed Rate (ABR) Baseline through end of study (53 months) The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (e.g., knee and ankle bleed following a fall) was counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) was reported.
Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes Baseline through end of study (53 months) The participant or caregiver rated the overall treatment response at 24 (+/- 2) hours after the initiation of treatment using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Change From Baseline in Pain Severity Baseline, end of study (53 months) Hemophilia symptom (haemo-SYM) questionnaire has two subscales: pain and bleed. It was used to asses the pain severity for participants \>=18 years of age as: pain because of swelling in my joints, climbing stairs, upon waking in the morning, active arthritis; constant pain, in my muscles, that needs medication; joint sensitivity to weather conditions; reduced range of joint movement, joint deformity, sleep disturbance because of pain or bleeds, blood in my urine, nose bleeds and assigned a score of 0=Absent, 1=very mild, 2=mild, 3=moderate, 4=severe and 5=very severe. The score was determined as (mean score/5)\*100 where mean score is the mean of the available results in the particular subscale. Higher scores on the Haemo-SYM indicate more severe symptoms. Therefore, negative change scores indicate that symptoms have improved. Here 'n' refers to the number of participants evaluable for this endpoint.
Total Time Intervals Between Bleeding Episodes Baseline through end of study (53 months) The time interval between bleeding episodes was calculated based upon the date and time reported for each bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII.
Average Dose of BAX 855 Per Prophylactic Infusion Baseline through end of study (53 months) The average dose of BAX 855 per prophylactic infusion was reported.
Change From Baseline in Blood Pressure Baseline, end of study (53 months) Change in systolic and diastolic blood pressure at pre-infusion and post-infusion at end of the study were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, SBP refers to systolic blood pressure, DBP refers to diastolic blood pressure.
Change From Baseline in Bleed Severity Baseline, end of study (53 months) Hemophilia symptom (haemo-SYM) questionnaire has two subscales: pain and bleed. It was used to asses the bleed severity for participants \>=18 years of age as: severity of spontaneous bleeding in my joints (unrelated to injury or activity), spontaneous bleeding in my muscles (unrelated to injury or activity), prolonged bleeding after injury in spite of treatment, intense pain because of bleeding event, joint pain due to active bleed and bleeding during personal hygiene routine, blood in my urine, nose bleeds and assigned a score of 0=Absent, 1=very mild, 2=mild, 3=moderate, 4=severe and 5=very severe. The score was determined as (mean score/5)\*100 where mean score is the mean of the available results in the particular subscale. Higher scores on the Haemo-SYM indicate more severe symptoms. Therefore, negative change scores indicate that symptoms have improved. Here 'n' refers to the number of participants evaluable for this endpoint.
BAX 855 Infusions Needed to Treat Bleeding Episodes Baseline through end of study (53 months) The BAX 855 infusions to treat each bleeding episode was determined by the participant, the participant's caregiver, and/or investigator, and was based upon the participant's response to treatment. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline through end of study (53 months) An AE was any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an investigational product (IP), whether or not considered causally related to the IP. A serious adverse event (SAE) was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death; was life-threatening; required inpatient hospitalization or resulted in prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was a medically important event.
Change From Baseline in Body Temperature Baseline, end of study (53 months) Change in body temperature at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.
Change From Baseline in Respiratory Rate Baseline, end of study (53 months) Change in respiratory rate at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.
Change From Baseline in Pulse Rate Baseline, end of study (53 months) Change in pulse rate at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36) Baseline, end of study (53 months) HRQoL in participants aged \>=14 years was measured using the SF-36 questionnaire. The questionnaire was divided into 8 domains and scored as: physical functioning (1=yes, limited a lot to 3=no, not limited at all), role-physical (1=all of the time to 5=none of the time), bodily pain (1=very severe to 6=none), general health (1=poor to 5=excellent), vitality (1=none of the time to 5=all of the time), social functioning (1=all of the time: to 5=none of the time), role emotional (1=all of the time to 5=none of the time) and mental health (1=all of the time to 5=none of the time). The score for each domain is then to be transformed to a 0-100 range as \[(actual raw score-lowest possible raw score)/possible raw score range\]\*100. Positive change scores indicate improved HRQoL. in the below table 'FDR' indicates fixed dose regimen, 'PK-tr' indicates pharmacokinetically tailored regimen and 'n' refers to the number of participants evaluable for this endpoint.
Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments. Baseline through end of study (53 months) The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen at the time of sampling, AlA refers to alanine aminotransferase, AP refers to alkaline phosphatase, AsA refers to aspartate aminotransferase.
Number of Participants With Shifts in Hematology Laboratory Assessments Baseline through end of study (53 months) The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, Leu refers to leukocytes, MCV refers to mean corpuscular volume, Lym/Leu refers to lymphocytes/leukocytes.
Number of Participants With Shifts in Lipid Panel Assessments Baseline through end of study (53 months) The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported.. In the below table, HDL refers to high density lipoprotein, LDL refers to low density lipoprotein, VLDL refers to very low density lipoprotein.
Number of Participants With Binding Antibodies Baseline through end of study (53 months) Binding antibodies (IgG and IgM) against FVIII, polyethylene glycol (PEG) and PEGylated FVIII (PEG-FVIII) were analyzed using enzyme-linked immunosorbent assay (ELISA).
Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies Baseline through end of study (53 months) Testing for binding of anti-CHO protein antibodies was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal antihuman IgG antibodies.
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Pediatrics Quality of Life (PedsQL) Questionnaire Baseline, end of study (53 months) HRQoL in participants aged \<14 years was measured using the PedsQL. It capture data for the following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial functioning, physical health and a total score. Each question of the PedsQL was scored as Never: 100, almost never: 75, sometimes: 50, often: 25, almost always: 0. The mean of the individual question scores was calculated. Lower scores on the PedsQL indicating worse HRQoL. Here, FDR refers to fixed dose regimen, PK-t R refers to PK-tailored regimen. Here 'n' refers to the number of participants evaluable for this endpoint. Here 'n' refers to the number of participants evaluable for this endpoint.
Trial Locations
- Locations (89)
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Bleeding and Clotting Disorders Institute
🇺🇸Peoria, Illinois, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
Children's Mercy Hospitals & Clinics
🇺🇸Kansas City, Missouri, United States
North Shore-Long Island Jewish Health System
🇺🇸New Hyde Park, New York, United States
Scroll for more (79 remaining)Phoenix Childrens Hospital🇺🇸Phoenix, Arizona, United States