Clinical trial NCT04565236: A Post Approval Commitment Study to Gain More Information on How Safe and Effective KOVALTRY is in Chinese Children, Adolescents /Adults With Severe Hemophilia A
Official title: A Post Approval Commitment Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of KOVALTRY in Chinese Children, Adolescents /Adults With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemophilia A
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 45
Sex: MALE
Minimum age (years): 0
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

Part A (PTPs):

* Chinese participants with severe hemophilia A (defined as Factor VIII (FVIII): C \< 1% with one- stage clotting assay documented at the time of screening)
* Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product
* For participants \< 12 years of age, ≥ 50 exposure days (ED); for participants ≥ 12 to 65 years of age, ≥ 150 ED with any FVIII product
* No current evidence of inhibitor
* No history of FVIII inhibitor formation
* Signed informed consent

Part B (PUPs/MTPs):

* Participants must be \<6 years of age at the time of their parent or legal representative's signature of informed consent on the participant's behalf
* Chinese participants with severe hemophilia A (defined as Factor VIII (FVIII): C \< 1% with one- stage clotting assay documented at the time of screening)
* PUPs must have no previous exposure to any FVIII product. MTPs must have no more than 1 ED with any purified FVIII concentrate or 3 exposures with FFP or cryoprecipitate.
* MTPs must have no current evidence of inhibitor antibody as measured by the Nijmegen-modified Bethesda assay (\<0.6 BU/mL) in 2 consecutive samples and must have absence of clinical signs or symptoms of decreased response to FVIII administration. Testing for the 2 negative samples must be performed by the central laboratory at least 1 week but not more than 2 weeks apart. Participants may not receive FVIII product within 72 hours prior to the collection of samples for inhibitor testing.
* PUPs and MTPs must observe a 6-month washout period if they have received subcutaneous factor substitution therapy (emicizumab).
* PUPs may be included if they will receive their first FVIII dose with KOVALTRY for treatment of first bleed and agree to start prophylaxis as part of their care. MTPs may be included if they agree to start prophylaxis as part of their care.

Exclusion Criteria:

Part A (PTPs):

* Any other bleeding disease that is different from hemophilia A (e.g. von Willebrand disease, hemophilia B)
* Platelet count \< 100 000/mm\^3
* Impaired renal function (serum creatinine \> 2.0 mg/dL) or active liver disease (alanine aminotransferase/aspartate aminotransferase \[ALT/AST\] \> 5x ULN)
* Human immunodeficiency virus (HIV) positive with an absolute CD4 lymphocyte cell count \< 250 cells/μL
* Known hypersensitivity to the active substance, mouse or hamster protein
* 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.
* Requiring any pre-medication to tolerate FVIII infusions (e.g. antihistamines)
* Currently participating in another investigational drug study, or having previously participated in a clinical study involving an investigational drug within 30 days of signing informed consent or participated in completed interventional clinical studies with BAY81-8973 (Kovaltry)
* Planned major surgery, defined as surgery with respiratory assistance and/or general anesthesia

Part B (PUPs/MTPs):

* Any other bleeding disease that is different from hemophilia A (e.g. von Willebrand disease, hemophilia B)
* Platelet count \< 100 000/mm\^3
* Impaired renal function (serum creatinine \>2× upper limit of normal \[ULN\]) or active liver disease (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>5× ULN) based on screening laboratory assessments
* MTPs with history of FVIII inhibitor formation
* Known hypersensitivity to the active substance, mouse or hamster protein
* First treatment with KOVALTRY for high risk bleeding situations (e.g., surgery, intracranial bleed) or requiring intensive or prolonged treatment
* 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.
* Requiring any pre-medication to tolerate FVIII infusions (e.g. antihistamines)
* Currently participating in another investigational drug study, or having previously participated in a clinical study involving an investigational drug within 30 days of signing informed consent or participated in completed interventional clinical studies with BAY 81-8973 (Kovaltry)
* Planned major surgery, defined as surgery with respiratory assistance and/or general anesthesia
* Unable to tolerate volume of blood draws required for study participation

Primary outcomes:
measure: Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A
timeFrame: Up to 6 months
measure: Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part B
timeFrame: Up to 48 hours post-infusion during 6 months
Secondary outcomes:
measure: Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A
timeFrame: Up to 48 hours post-infusion during 6 months
measure: Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B
timeFrame: Up to 51 exposure days
measure: Number of Infusions Per Bleeding Episode
timeFrame: Part A: up to 6 months; Part B: up to 51 exposure days
measure: Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery
timeFrame: Part A: up to 6 months; Part B: up to 51 exposure days
measure: FVIII In-vivo Recovery in Part B
timeFrame: At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days
measure: Factor VIII Inhibitor Development by the Nijmegen Bethesda Assay
timeFrame: Part A: up to 6 months; Part B: up to 51 exposure days
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Part A: up to 6 months; Part B: up to 51 exposure days
measure: FVIII In-vivo Recovery in Part A
timeFrame: At baseline, Month 2 and final visit, up to 6 months
measure: Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A
timeFrame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
measure: Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A
timeFrame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
measure: Half-life (t1/2) of FVIII in Plasma in Part A
timeFrame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
Other outcomes:
measure: Number of Participants Without Bleeding Episode
timeFrame: During prophylaxis treatment in Part A: up to 6 months; Part B: up to 51 exposure days
measure: Number of Bleeds Per Assessment of Response to Treatment of Bleeds
timeFrame: Part A: up to 6 months; Part B: up to 51 exposure days
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
state: Beijing
city: Hangzhou
country: China
facility: The Children's Hospital Zhejiang University School of Med
state: Hangzhou Province
city: Shijiazhuang
country: China
facility: Shijiazhuang General Hospital
state: Hebei
city: Nanjing
country: China
facility: NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
state: Jiangsu
city: Suzhou
country: China
facility: 1st Affiliated hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Taiyuan
country: China
facility: Children's Hospital of Shanxi
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Women & Children's Central Hospital
state: Sichuan
city: Beijing
country: China
facility: Peking Union Medical College Hospital CAMS
city: Shanghai
country: China
facility: Childrens Hospital of Shanghai
Study officials:
References: