The goal of this study is to gather more information on safety and efficacy of Kovaltry for the prevention and treatment of bleeds in Chinese children, adolescents/adults with severe hemophilia A. In addition, pharmacokinetic parameters of Kovaltry will be assessed in a subset of patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
25 to 50 IU of Kovaltry per kg body weight given via intravenous (IV) infusion twice weekly, three times weekly, or every other day according to individual requirements for 6 months. The dose decisions are at the discretion of the investigator.
12 year-old: 25 to 50 IU of Kovaltry per kg body weight given via intravenous (IV) infusion twice weekly, three times weekly, or every other day for 6 months. \>12 year-old: 20 to 40 IU of Kovaltry per kg of body weight given via intravenous (IV) infusion two or three times per week for 6 months. The dose decisions are at the discretion of the investigator.
Beijing Children's Hospital, Capital Medical University
Beijing, Beijing Municipality, China
The Children's Hospital Zhejiang University School of Med
Hangzhou, Hangzhou Province, China
Shijiazhuang General Hospital
Shijiazhuang, Hebei, China
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A
Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred during the prophylaxis treatment period is reported for previously treated patients (PTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.
Time frame: Up to 6 months
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part B
Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred within 48 hours of previous prophylaxis infusion is reported for previously untreated/minimally treated patients (PUPs/MTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.
Time frame: Up to 48 hours post-infusion during 6 months
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A
Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred within 48 hours of previous prophylaxis infusion is reported for previously treated patients (PTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.
Time frame: Up to 48 hours post-infusion during 6 months
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B
Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred during the prophylaxis treatment period is reported for previously untreated/minimally treated patients (PUPs/MTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.
Time frame: Up to 51 exposure days
Number of Infusions Per Bleeding Episode
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15 to 50 IU of Kovaltry per kg body weight (minimum dose: 250 IU) given via intravenous (IV) infusions at least once a week. The dose decisions are at the discretion of the investigator.
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
Nanjing, Jiangsu, China
1st Affiliated hospital of Soochow University
Suzhou, Jiangsu, China
Jiangxi Provincial People's Hospital
Nanchang, Jiangxi, China
Children's Hospital of Shanxi
Taiyuan, Shanxi, China
Chengdu Women & Children's Central Hospital
Chengdu, Sichuan, China
Peking Union Medical College Hospital CAMS
Beijing, China
Childrens Hospital of Shanghai
Shanghai, China
The mean value of number of infusions for the treatment of one bleed to achieve hemostasis is reported.
Time frame: Part A: up to 6 months; Part B: up to 51 exposure days
Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery
For participants who underwent minor surgeries during the study, investigators were ask to assess the adequacy of hemostasis during the surgeries as excellent, good, moderate or poor. Number of surgeries per assessment is reported.
Time frame: Part A: up to 6 months; Part B: up to 51 exposure days
FVIII In-vivo Recovery in Part B
Incremental recovery of Factor VIII (FVIII) was determined by collecting blood samples pre-infusion and 15-30 minutes after the end of the infusion. Mean recovery values at different time points are reported.
Time frame: At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days
Factor VIII Inhibitor Development by the Nijmegen Bethesda Assay
Number of participants who developed a positive Factor VIII (FVIII) inhibitor level (≥0.6 Bethesda unit \[BU/mL\]) during the study is reported.
Time frame: Part A: up to 6 months; Part B: up to 51 exposure days
Number of Participants With Treatment-emergent Adverse Events
An adverse event (AE) was any untoward medical occurrence in a participant, associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect; another medical important serious event as judged by the investigator. AEs or SAEs were considered to be treatment emergent (TEAEs or TESAEs) if they started after the first KOVALTRY infusion and up to 3 days after the last dose.
Time frame: Part A: up to 6 months; Part B: up to 51 exposure days
FVIII In-vivo Recovery in Part A
Incremental recovery of Factor VIII (FVIII) was determined by collecting blood samples pre-infusion and 15-30 minutes after the end of the infusion. Mean recovery values at different time points are reported.
Time frame: At baseline, Month 2 and final visit, up to 6 months
Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A
For the assessment, participants were administered a dose of 50 IU/kg KOVALTRY. Participants must have no signs or symptoms of an acute bleeding episode. For participants below 12 years, the evaluation was only performed once at baseline. For adolescents/adult participants 12 years or older, the evaluation was performed twice at baseline and at final visit.
Time frame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A
For the assessment, participants were administered a dose of 50 IU/kg KOVALTRY. Participants must have no signs or symptoms of an acute bleeding episode. For participants below 12 years, the evaluation was only performed once at baseline. For adolescents/adult participants 12 years or older, the evaluation was performed twice at baseline and at final visit.
Time frame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
Half-life (t1/2) of FVIII in Plasma in Part A
For the assessment, participants were administered a dose of 50 IU/kg KOVALTRY. Participants must have no signs or symptoms of an acute bleeding episode. For participants below 12 years, the evaluation was only performed once at baseline. For adolescents/adult participants 12 years or older, the evaluation was performed twice at baseline and at final visit.
Time frame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years