A Long-term Study of ADYNOVI/ADYNOVATE in Participants With Haemophilia A

• ADYNOVI/ADYNOVATE (Biological), also known as Antihaemophilic Factor [Recombinant] PEGylated rurioctocog alfa pegol, TAK-660, BAX 855: Participants will receive ADYNOVI/ADYNOVATE prescribed prophylactically by physicians based on their standard clinical practice and in accordance with the national SmPC.

Primary outcomes

• Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Throughout the study period (approximately up to 10 years)]: An SAE is any untoward medical occurrence (whether considered to be related to study product or not) that at any dose results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality or birth defect, an important medical event. An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical (study) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (study) product, whether or not related to the medicinal (study) product. AEs and SAEs that are at least possibly related to study drug ADYNOVI/ADYNOVATE will be evaluated in this outcome.
• Number of Participants With Adverse Events of Special Interest (AESI) [Throughout the study period (approximately up to 10 years)]: Adverse events of special interest are as follows: thromboembolic events, hypersensitivity reactions, lack of efficacy and confirmed FVIII inhibitor development.
• Number of Participants With Adverse Events (AE) Related to Impaired Renal Function [Throughout the study period (approximately up to 10 years)]: An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical (study) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (study) product, whether or not related to the medicinal (study) product. AEs (at least possibly related) that are potentially indicative of or related to long-term effects of PEG accumulation impaired renal function will be evaluated in this outcome.
• Number of Participants With Adverse Events (AE) Related to Impaired Hepatic Function [Throughout the study period (approximately up to 10 years)]: An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical (study) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (study) product, whether or not related to the medicinal (study) product. AEs (at least possibly related) that are potentially indicative of or related to long-term effects of PEG accumulation impaired hepatic function will be evaluated in this outcome.
• Number of Participants With Adverse Events (AE) Related to Impaired Neurologic Function [Throughout the study period (approximately up to 10 years)]: An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical (study) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (study) product, whether or not related to the medicinal (study) product. AEs (at least possibly related) that are potentially indicative of or related to long-term effects of PEG accumulation impaired neurologic function will be evaluated in this outcome.

Secondary outcomes

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Specified Time Points [Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10]: eGFR levels will be assessed from baseline to end of the study at every visit. Note: all assessments are being done as per Standard of Care (SOC) at each study site/ center and are not mandatory.
• Change From Baseline in Alanine Aminotransferase (ALT) at Specified Time Points [Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10]: ALT levels will be assessed from baseline to end of the study at every visit. Note: all assessments are being done as per Standard of Care (SOC) at each study site/ center and are not mandatory.
• Change From Baseline in Bilirubin at Specified Time Points [Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10]: Bilirubin levels will be assessed from baseline to end of the study at every visit. Note: all assessments are being done as per Standard of Care (SOC) at each study site/ center and are not mandatory.
• Change From Baseline in Polyethylene Glycol (PEG) Plasma Levels at Specified Time Points [Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10]: PEG plasma levels will be assessed from baseline to end of the study at every visit. Note: all assessments are being done as per Standard of Care (SOC) at each study site/ center and are not mandatory.
• Number of Participants With Clinically Significant Abnormalities in Vital Signs [Throughout the study period (approximately up to 10 years)]: Clinically significant abnormal findings in vital signs, collected as part of standard of care (SOC)/ standard clinical practice.
• Number of Participants With Clinically Significant Abnormalities in Physical Exam [Throughout the study period (approximately up to 10 years)]: Clinically significant abnormal findings in physical exam collected as part of standard of care (SOC)/ standard clinical practice.
• Number of Participants With Clinically Significant Abnormalities in Neurological Exam [Throughout the study period (approximately up to 10 years)]: Clinically significant abnormal findings in neurological exam collected as part of standard of care (SOC)/ standard clinical practice.
• Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters [Throughout the study period (approximately up to 10 years)]: Clinically significant abnormal findings in clinical laboratory parameters collected as part of standard of care (SOC)/ standard clinical practice.

Sex: All

Inclusion Criteria

* Signed informed consent obtained from participant and/or legally authorised representative before any study related activities (any procedure related to recording of data according to the protocol).
* Participant at any age with haemophilia A prescribed ADYNOVI/ADYNOVATE prophylaxis.
* Negative factor VIII (FVIII) inhibitor test at study entry.
* Decision to initiate treatment with commercially available ADYNOVI/ADYNOVATE has been made by the participant and/or legally authorised representative and the treating physician before and independently from the decision to include the participant in this study.

Exclusion Criteria

* Previous participation in this study. Participation is defined as signed informed consent.
* Known or suspected hypersensitivity to ADYNOVI/ADYNOVATE or related products.
* Mental incapacity, unwillingness or other barriers precluding adequate understanding or cooperation.

• Study Director, Study director, Takeda