TOPIK Study: A Study to Report Progressive Multifocal Leukoencephalopathy and Other Serious Opportunistic Infections in Natalizumab Treated Participants

Long-term Surveillance of Patients With Multiple Sclerosis to Report Progressive Multifocal Leukoencephalopathy and Other Serious Opportunistic Infections Among Patients Treated With Natalizumab

The primary objective of the study is to estimate the incidence of progressive multifocal leukoencephalopathy (PML) and serious adverse events (SAEs) of other opportunistic infections (OIs) among all participants taking natalizumab. The secondary objectives of the study are to estimate the incidence of SAEs, to estimate the incidence of SAEs among participant subgroups defined by demographic and clinical factors (age, gender, duration of treatment, pregnancy, breastfeeding), to characterize and estimate incidences of malignancies, hypersensitivity reactions and John Cunningham Virus (JCV) positivity among all participants taking natalizumab, and to count and describe pregnancies and breastfeeding among participants previously exposed to natalizumab.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Natalizumab

• Study Type: Observational
• Enrollment (Actual): 675

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • Fakultni nemocnice Brno
  • Brno, Czechia
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia
    • Fakultni Nemocnice Hradec Kralove
  • Jihlava, Czechia
    • Nemocnice Jihlava
  • Olomouc, Czechia
    • Fakultni nemocnice Olomouc
  • Ostrava, Czechia
    • Fakultní nemocnice v Ostravě
  • Pardubice, Czechia
    • Nemocnice Pardubického kraje
  • Pilsen, Czechia
    • Fakultní nemocnice v Plzni
  • Prague, Czechia
    • Vseobecna Fakultni Nemocnice V Praze
  • Prague, Czechia
    • Fakultní nemocnice Královské Vinohrady v Praze
  • Prague, Czechia
    • Fakultní nemocniceMotol v Praze
  • Prague, Czechia
    • Fakultní Thomayerova nemocnice v Praze v Krči
  • Teplice, Czechia
    • Nemocnice Teplice
  • Zlín, Czechia
    • Krajská nemocnice T. Bati ve Zlíně
  • České Budějovice, Czechia
    • Nemocnice Ceske Budejovice

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study will include participants with MS who are treated with natalizumab from the 1st of January 2019 and participating in the Czech National MS registry (ReMuS).

Description

Key Inclusion Criteria:

• Participants starting with natalizumab after 1st January 2019 and participating in the ReMuS will be included in this study

Key Exclusion Criteria:

• Not Applicable (NA)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Natalizumab Cohort; The cohort will include participants with MS who are newly treated with natalizumab (administered as a standard of care/routine clinical practice) from 1st January 2019 including those participants who terminate or discontinue the treatment during the observational period.	Drug: Natalizumab; Administered as specified in the treatment arm.; Other Names: Tysabri

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progressive Multifocal Leukoencephalopathy (PML) who are Taking Natalizumab		Up to 6 years
Number of Participants with Serious Adverse Events (SAEs) of Other Opportunistic Infections (OIs) who are Taking Natalizumab	SAE means such adverse event that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in permanent or significant damage to health or limitation of capabilities or is manifested as a congenital anomaly or birth defect in offspring, irrespective of the administered dose of the medicinal product. Serious OI means such OI which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in permanent or significant damage to health or limitation of capabilities or is manifested as a birth defect in offspring.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With SAEs	SAE means such adverse event that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in permanent or significant damage to health or limitation of capabilities or is manifested as a congenital anomaly or birth defect in offspring, irrespective of the administered dose of the medicinal product.	Up to 6 years
Number of Participants With SAEs Among Participant Subgroups Defined by Demographic and Clinical Factors	SAE means such adverse event that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in permanent or significant damage to health or limitation of capabilities or is manifested as a congenital anomaly or birth defect in offspring, irrespective of the administered dose of the medicinal product. Demographic and clinical factors involve age, gender, duration of treatment, pregnancy, breastfeeding.	Up to 6 years
Number of Participants With Malignancies who are Taking Natalizumab		Up to 6 years
Number of Participants With Hypersensitivity Reactions who are Taking Natalizumab		Up to 6 years
Number of Participants who are John Cunningham Virus (JCV) Positive and Taking Natalizumab		Up to 6 years
Number of Pregnant and Breastfeeding Participants who Were Previously Exposed to Natalizumab		Up to 6 years

Collaborators and Investigators

• Sponsor: Biogen
• Collaborators: ReMuS Registry
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 8, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Progressive Multifocal Leukoencephalopathy (PML)
• Additional Relevant MeSH Terms: Infectious Encephalitis; Neuroinflammatory Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Infections; Virus Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; DNA Virus Infections; Slow Virus Diseases; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Polyomavirus Infections; Encephalitis; Multiple Sclerosis; Sclerosis; Leukoencephalopathy, Progressive Multifocal; Leukoencephalopathies; Opportunistic Infections; Immunologic Factors; Physiological Effects of Drugs; Natalizumab
• Other Study ID Numbers: CZ-TYS-12155

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

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