Trial Outcomes & Findings for 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 (NCT NCT04565236)

NCT ID: NCT04565236

Last Updated: 2025-04-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 45 participants
• Primary outcome timeframe: Up to 6 months
• Results posted on: 2025-04-18

Participant Flow

The Part A of study was conducted in multicenter in China between 22 SEP 2020 and 04 JAN 2022. The Part B of study was conducted in multicenter in China between 07 SEP 2021 and 15 MAR 2024.

A total of 44 subjects were enrolled in Part A of the study. Of these, 2 subjects did not pass screening and 42 subjects participated in Part A. A total of 3 participants were enrolled in Part B of the study, and all of them passed screening.

Participant milestones

Measure	Part A: PTPs <12 Years Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part A: PTPs ≥12 Years Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Overall Study STARTED	30	12	2	1
Overall Study COMPLETED	30	12	1	1
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Measure	Part A: PTPs <12 Years Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part A: PTPs ≥12 Years Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Overall Study Patient/Guardian Decision	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Part A: PTPs <12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part A: PTPs ≥12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part B: PUPs <6 Years n=2 Participants Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 Participants Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.	Total n=45 Participants Total of all reporting groups
Age, Customized Infants and toddlers (28 days-23 months)	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Customized Children (2-11 years)	30 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	32 Participants n=21 Participants
Age, Customized Adolescents (12-17 years)	0 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Age, Customized Adults (18-64 years)	0 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	7 Participants n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	12 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	45 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	30 Participants n=5 Participants	12 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	45 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 6 months

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A	1.86 Bleed per year Standard Deviation 2.54 • Interval 2.54 to	3.38 Bleed per year Standard Deviation 4.17 • Interval 4.17 to	—	—

PRIMARY outcome

Timeframe: Up to 48 hours post-infusion during 6 months

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=2 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=1 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part B	0.00 Bleed per year Standard Deviation 0.00 • Interval 0.0 to	0.00 Bleed per year Standard Deviation 0.00 • Interval 0.0 to	—	—

SECONDARY outcome

Timeframe: Up to 48 hours post-infusion during 6 months

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A	2.26 Bleed per year Standard Deviation 3.10 • Interval 3.1 to	1.36 Bleed per year Standard Deviation 2.19 • Interval 2.19 to	—	—

SECONDARY outcome

Timeframe: Up to 51 exposure days

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=2 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=1 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B	1.13 Bleed per year Standard Deviation 1.60 • Interval 1.6 to	2.05 Bleed per year Standard Deviation 0 • Interval 0.0 to	—	—

SECONDARY outcome

Timeframe: Part A: up to 6 months; Part B: up to 51 exposure days

The mean value of number of infusions for the treatment of one bleed to achieve hemostasis is reported.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=17 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=5 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=1 Participants Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 Participants Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Number of Infusions Per Bleeding Episode	1.78 Infusion Standard Deviation 2.28 • Interval 2.28 to	1.45 Infusion Standard Deviation 1.29 • Interval 1.29 to	14.00 Infusion Standard Deviation 0.00 • Interval 0.0 to	1.00 Infusion Standard Deviation 0.00 • Interval 0.0 to

SECONDARY outcome

Timeframe: Part A: up to 6 months; Part B: up to 51 exposure days

Population: Participants with 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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=2 surgeries Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=2 surgeries Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery Total minor surgeries	2 surgery	2 surgery	—	—
Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery Surgeries with EXCELLENT adequacy of hemostasis	2 surgery	2 surgery	—	—

SECONDARY outcome

Timeframe: At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days

Population: The Part B PUP participant who discontinued didn't have any measurements for recovery calculation and therefore wasn't included in recovery analysis.

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=1 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=1 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
FVIII In-vivo Recovery in Part B Baseline (Unscheduled visit for PUP)	1.90 IU/dL per IU/kg Standard Deviation 0.00	1.86 IU/dL per IU/kg Standard Deviation 0.00	—	—
FVIII In-vivo Recovery in Part B Visit 6 (ED 20)	0.91 IU/dL per IU/kg Standard Deviation 0.00	1.22 IU/dL per IU/kg Standard Deviation 0.00	—	—
FVIII In-vivo Recovery in Part B Final visit	1.55 IU/dL per IU/kg Standard Deviation 0.00	—	—	—

SECONDARY outcome

Timeframe: Part A: up to 6 months; Part B: up to 51 exposure days

Number of participants who developed a positive Factor VIII (FVIII) inhibitor level (≥0.6 Bethesda unit [BU/mL]) during the study is reported.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=2 Participants Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 Participants Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Factor VIII Inhibitor Development by the Nijmegen Bethesda Assay	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part A: up to 6 months; Part B: up to 51 exposure days

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=2 Participants Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 Participants Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Number of Participants With Treatment-emergent Adverse Events Any TEAE	13 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events Maximum intensity for any TEAE - Mild	10 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events Maximum intensity for any TEAE - Moderate	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Maximum intensity for any TEAE - Severe	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Any study drug-related TEAE	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Any TESAE	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events TEAE with outcome death	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At baseline, Month 2 and final visit, up to 6 months

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
FVIII In-vivo Recovery in Part A Baseline	1.82 IU/dL per IU/kg Standard Deviation 0.26	2.03 IU/dL per IU/kg Standard Deviation 0.46	—	—
FVIII In-vivo Recovery in Part A Month 2	1.86 IU/dL per IU/kg Standard Deviation 0.32	2.12 IU/dL per IU/kg Standard Deviation 0.42	—	—
FVIII In-vivo Recovery in Part A Final visit	1.85 IU/dL per IU/kg Standard Deviation 0.33	2.06 IU/dL per IU/kg Standard Deviation 0.37	—	—

SECONDARY outcome

Timeframe: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

Population: The number of analyzed participants in group "Part A: PTPs \<12 years" for category "Final Visit/ Early " is 0 because no evaluation was performed.

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A Baseline	95.20 IU/dL Geometric Coefficient of Variation 15.24	114.64 IU/dL Geometric Coefficient of Variation 15.77	—	—
Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A Final Visit/ Early Termination	—	115.95 IU/dL Geometric Coefficient of Variation 17.47	—	—

SECONDARY outcome

Timeframe: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

Population: The number of analyzed participants in group "Part A: PTPs \<12 years" for category "Final Visit/ Early " is 0 because no evaluation was performed.

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A Baseline	1292.97 h*IU/dL Geometric Coefficient of Variation 22.87	1519.38 h*IU/dL Geometric Coefficient of Variation 32.38	—	—
Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A Final Visit/ Early Termination	—	1559.29 h*IU/dL Geometric Coefficient of Variation 26.16	—	—

SECONDARY outcome

Timeframe: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

Population: The number of analyzed participants in group "Part A: PTPs \<12 years" for category "Final Visit/ Early " is 0 because no evaluation was performed

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.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Half-life (t1/2) of FVIII in Plasma in Part A Baseline	10.3655 Hour Geometric Coefficient of Variation 21.22	11.8605 Hour Geometric Coefficient of Variation 19.25	—	—
Half-life (t1/2) of FVIII in Plasma in Part A Final Visit/ Early Termination	—	11.2630 Hour Geometric Coefficient of Variation 17.29	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: During prophylaxis treatment in Part A: up to 6 months; Part B: up to 51 exposure days

Number of participants who did not experience any bleed during the prophylaxis treatment period or within 48 hours of previous prophylaxis infusion is reported.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=2 Participants Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 Participants Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Number of Participants Without Bleeding Episode During prophylaxis treatment	13 Participants	7 Participants	1 Participants	0 Participants
Number of Participants Without Bleeding Episode Within 48 hours	16 Participants	8 Participants	2 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Part A: up to 6 months; Part B: up to 51 exposure days

Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Number of bleeds per assessment is reported.

Outcome measures

Measure	Part A: PTPs ≥12 Years n=30 Participants Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment.	Part A: PTPs <12 Years n=12 Participants Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=2 Participants Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 Participants Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Number of Bleeds Per Assessment of Response to Treatment of Bleeds Total bleeds	51 Bleeds	11 Bleeds	1 Bleeds	1 Bleeds
Number of Bleeds Per Assessment of Response to Treatment of Bleeds Bleeds without response assessment to treatment	7 Bleeds	1 Bleeds	0 Bleeds	0 Bleeds
Number of Bleeds Per Assessment of Response to Treatment of Bleeds Bleeds with EXCELLENT response to treatment	4 Bleeds	5 Bleeds	0 Bleeds	0 Bleeds
Number of Bleeds Per Assessment of Response to Treatment of Bleeds Bleeds with GOOD response to treatment	25 Bleeds	2 Bleeds	0 Bleeds	1 Bleeds
Number of Bleeds Per Assessment of Response to Treatment of Bleeds Bleeds with MODERATE response to treatment	14 Bleeds	3 Bleeds	1 Bleeds	0 Bleeds
Number of Bleeds Per Assessment of Response to Treatment of Bleeds Bleeds with POOR response to treatment	1 Bleeds	0 Bleeds	0 Bleeds	0 Bleeds

Adverse Events

Part A: PTPs >=12 Years

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: PTPs <12 Years

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Part B: PUPs <6 Years

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part B: MTPs <6 Years

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: PTPs >=12 Years n=12 participants at risk Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment	Part A: PTPs <12 Years n=30 participants at risk Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=2 participants at risk Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 participants at risk Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	3.3% 1/30 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Nervous system disorders Epilepsy	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	3.3% 1/30 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.

Other adverse events

Measure	Part A: PTPs >=12 Years n=12 participants at risk Previously treated severe hemophilia A patients (PTPs) aged 12 to 65 years received KOVALTRY for prophylaxis and treatment	Part A: PTPs <12 Years n=30 participants at risk Previously treated severe hemophilia A patients (PTPs) aged below 12 years received KOVALTRY prophylaxis and treatment.	Part B: PUPs <6 Years n=2 participants at risk Previously untreated severe hemophilia A patients (PUPs) aged below 6 years of age received KOVALTRY for prophylaxis and treatment.	Part B: MTPs <6 Years n=1 participants at risk Minimally treated severe hemophilia A patients (MTPs) aged below 6 years received KOVALTRY for prophylaxis and treatment.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	50.0% 1/2 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Gastrointestinal disorders Duodenal ulcer	8.3% 1/12 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Infections and infestations Tonsillitis	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	13.3% 4/30 • Number of events 4 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Infections and infestations Upper respiratory tract infection	8.3% 1/12 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	16.7% 5/30 • Number of events 10 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Infections and infestations Respiratory tract infection	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	100.0% 1/1 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Infections and infestations COVID-19	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	100.0% 1/1 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	50.0% 1/2 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/12 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	50.0% 1/2 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.
Vascular disorders Hypertension	8.3% 1/12 • Number of events 1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/30 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/2 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.	0.00% 0/1 • From the first infusion to three days after last infusion, an average of 6 months for Part A and 4 months for Part B. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact. Adverse event reporting for deaths (all causes) considers all deaths that occurred at any time during the study before the last contact.

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PI shall ensure that any manuscripts of publications related to the study or the results of the study are provided to Bayer for review at least 60 working days before publication, during which time the PI shall maintain confidentiality. If Bayer does not make any comments within the 60 working days, the PI is free to publish. Within 60 working days, Bayer may propose amendments to the publication and reach a consensus with the PI."
• Publication restrictions are in place

Restriction type: OTHER