Prospective, Non-interventional Study to Evaluate Immunogenicity of AryoSeven

A Post-Marketing, Observational Study in Iran to Determine the Immunogenicity Status in Patients Who Have Received rFVIIa AryoSeven.

This study evaluates the immunogenicity of the biosimilar rFVIIa (AryoSeven) in subjects receiving AryoSeven in real-life clinical practice.

Study Overview

• Status: Completed
• Conditions: Factor VII Deficiency; Hemophilia A With Inhibitor; Hemophilia B With Inhibitor; Glanzmann's Thrombasthenia

Detailed Description

This is a Non-interventional, observational, prospective evaluation of immunogenicity (neutralizing antibodies toward FVII) of patients with Hemophilia A or B with inhibitors, Factor VII Deficiency, Glanzmann's thrombasthenia, who have received one or more dose of AryoSeven in the daily practice. This study is conducted in Iran where AryoSeven is available on the market since 21-8-2012 and NovoSeven is no longer available since 2013. Patients will be retrieved from the Iranian Registry of Hemophilia patients of MATHA (Iranian Hemophilia and Thrombophilia Association, Tehran, Iran). The Registry Patient Screener will sequentially review patients in the Registry to identify patients who have received treatment with AryoSeven, in reverse chronological order of inclusion in the registry, starting from a date 6 months prior to the date of this study and until when the sample size to enroll (200 patients) is completed.

Patients identified will be called for a visit (Screening visit) for providing informed consent, interview, and blood sampling collection for prospective immunogenicity testing. Retrospective data collection, including previous immunogenicity status and the number of exposure days, will be performed on hospital records, patient diary. Immunogenicity will be tested by a centralized laboratory in Iran using the PT-based Bethesda assay.

Patients will be enrolled if they had an immunogenicity test negative, performed at the earliest time after NovoSeven was no longer available in Iran. Patients who do not have a previous negative immunogenicity test will be enrolled if negative at immunogenicity test performed during screening for this study.

Patients enrolled will be followed for at least 12 months for immunogenicity and Adverse Drug Reactions.

Patients who have a positive previous immunogenicity test or results positive at immunogenicity test performed at Screening (patients without a previous immunogenicity test), will not be enrolled, but registered and followed for 12 months (or longer) to collect data on the natural history of their disease.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Iranian Blood Transfusion Organization (IBTO)
  • Tehran, Iran, Islamic Republic of
    • MAHTA (Iranian Hemophilia and Thrombophilia Association)

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with Hemophilia A or B with inhibitors, Factor VII Deficiency, Glanzmann's thrombasthenia, who have received one or more dose of AryoSeven in the daily practice and are negative at immunogenicity testing (antibodies neutralizing FVII).

Description

Inclusion Criteria:

• Patients with Hemophilia A or B with inhibitors, Factor VII Deficiency, Glanzmann's thrombasthenia
• Treated with AryoSeven in the daily practice,
• Signed informed consent (parents for children).
• an immunogenicity test negative, performed at the earliest time after NovoSeven was no longer available in Iran. Patients who do not have a previous negative immunogenicity test should be enrolled if negative at immunogenicity test performed during screening for this study.

Exclusion Criteria:

• Patients who received NovoSeven for any indication at any time before inclusion in the study, until an immunogenicity test excluded the development of immunogenicity related to NovoSeven.
• Parallel participation in another experimental drug trial.
• Parallel participation in another marketed drug trial (except for AryoSeven) that may affect the immunogenicity endpoint of the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity (neutralising antibodies toward FVII)	Immunogenicity will be assessed with the PT based Bethesda assay. In case of positive results, an inhibitor retesting using a second separately drawn sample as confirmatory measurement will be performed by a different specialised laboratory.	On plasma samples obtained 12 months after patient inclusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Drug Reactions	Adverse Drug Reactions related to the administration of AryoSeven reported by patients.	Adverse Drug Reactions will be monitored throughout the trial, from patient inclusion up to 12 months follow-up.

Collaborators and Investigators

• Sponsor: AryoGen Pharmed Co.
• Investigators: Study Director: Mohammad Faranoush, MD, Hazrat Rasool Akram Hospital, MAHAK Children's Hospital, Iran University of Medical Sciences, Tehran

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2016
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 14, 2017

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: July 1, 2020

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; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Blood Platelet Disorders; Hemophilia A; Hemophilia B; Factor VII Deficiency; Thrombasthenia
• Other Study ID Numbers: ARY2016-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No