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

Evaluation of Long-term Safety of ADYNOVI/ADYNOVATE (Antihaemophilic Factor [Recombinant] PEGylated, Rurioctocog Alfa Pegol) in Patients With Haemophilia A - An ADYNOVI/ADYNOVATE Post-Authorisation Safety Study (PASS)

The main aim of this study is to check for long-term side effects from ADYNOVI/ADYNOVATE prophylaxis in participants with haemophilia A when used under standard clinical practice in the real-world clinical setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: ADYNOVI/ADYNOVATE

• Study Type: Observational
• Enrollment (Actual): 207

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1527
    • SHAT of Oncohaematology Diseases
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Clinical Hospital Sveti Duh
  • Zagreb, Croatia, 1000
    • University Hospital Centre Zagreb
• Czechia
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole
  • Usti nad Labem, Czechia, 40113
    • Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshain
  • Bonn, Germany, 53127
    • Universitaetsklinikum Bonn AoeR
  • Hannover, Germany, 30159
    • Werlhof-Institut GmbH
  • Baden Wuerttemberg
    • Heidelberg, Baden Wuerttemberg, Germany, D-69123
      • SRH Kurpfalzkrankenhaus Heidelberg GmbH
• Hungary
  • Budapest, Hungary, 1134
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary, 1089
    • Heim Pal Orszagos Gyermekgyogyaszati Intezet
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem
  • Mohacs, Hungary, 7700
    • Mohacsi Korhaz
  • Nyiregyhaza, Hungary, 4400
    • SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
  • Pecs, Hungary, 7624
    • Pecsi Tudomanyegyetem Klinikai Kozpont
• Italy
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Roma, Italy, 161
    • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
  • Torino, Italy, 10126
    • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
• Korea, Republic of
  • Seoul, Korea, Republic of, 134-727
    • Kyung Hee University Hospital at Gangdong
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Centre Groningen-UMCG
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Las Palmas, Spain, 35010
    • Hospital Universitario de Gran Canaria Dr. Negrin
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07120
      • Hospital Universitari Son Espases
• Sweden
  • Göteborg, Sweden, 41345
    • Sahlgrenska Universitetssjukhuset
• Taiwan
  • Taipei, Taiwan, 11490
    • Tri-service general hospital
  • Taipei, Taiwan, 10449
    • MacKay Memorial Hospital_Tamsui Branch
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital, Linkou
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital
  • Bangkoknoi Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Shands Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Up to 200 participants with haemophilia A will be enrolled. The study will be conducted in European, North American and Asian countries.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Haemophilia A Group; Participants with haemophilia A in the study will receive ADYNOVI/ADYNOVATE prescribed prophylactically by physicians based on their standard clinical practice and in accordance with the national summary of product characteristics (SmPC).	Biological: ADYNOVI/ADYNOVATE; Participants will receive ADYNOVI/ADYNOVATE prescribed prophylactically by physicians based on their standard clinical practice and in accordance with the national SmPC.; Other Names: BAX 855; TAK-660; Antihaemophilic Factor [Recombinant] PEGylated rurioctocog alfa pegol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	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.	Throughout the study period (approximately up to 10 years)
Number of Participants With Adverse Events of Special Interest (AESI)	Adverse events of special interest are as follows: thromboembolic events, hypersensitivity reactions, lack of efficacy and confirmed FVIII inhibitor development.	Throughout the study period (approximately up to 10 years)
Number of Participants With Adverse Events (AE) Related to Impaired Renal Function	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.	Throughout the study period (approximately up to 10 years)
Number of Participants With Adverse Events (AE) Related to Impaired Hepatic Function	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.	Throughout the study period (approximately up to 10 years)
Number of Participants With Adverse Events (AE) Related to Impaired Neurologic Function	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.	Throughout the study period (approximately up to 10 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Specified Time Points	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.	Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10
Change From Baseline in Alanine Aminotransferase (ALT) at Specified Time Points	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.	Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10
Change From Baseline in Bilirubin at Specified Time Points	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.	Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10
Change From Baseline in Polyethylene Glycol (PEG) Plasma Levels at Specified Time Points	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.	Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10
Number of Participants With Clinically Significant Abnormalities in Vital Signs	Clinically significant abnormal findings in vital signs, collected as part of standard of care (SOC)/ standard clinical practice.	Throughout the study period (approximately up to 10 years)
Number of Participants With Clinically Significant Abnormalities in Physical Exam	Clinically significant abnormal findings in physical exam collected as part of standard of care (SOC)/ standard clinical practice.	Throughout the study period (approximately up to 10 years)
Number of Participants With Clinically Significant Abnormalities in Neurological Exam	Clinically significant abnormal findings in neurological exam collected as part of standard of care (SOC)/ standard clinical practice.	Throughout the study period (approximately up to 10 years)
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters	Clinically significant abnormal findings in clinical laboratory parameters collected as part of standard of care (SOC)/ standard clinical practice.	Throughout the study period (approximately up to 10 years)

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Investigators: Study Director: Study Director, Shire

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII; BAX 855
• Other Study ID Numbers: TAK-660-403; EUPAS35698 (Registry Identifier: EUPAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes