The CLARION study design and status update: a long-term, registry-based study evaluating adverse events of special interest in patients with relapsing multiple sclerosis newly started on cladribine tablets

Abstract

Objective

To describe the design of the CLARION post-approval safety study (EU PAS Register number, EUPAS24484) and provide a status update, including characteristics of patients included up to 1 May 2021.

Methods

CLARION aims to further evaluate adverse events of special interest in patients who are newly initiating treatment with cladribine tablets for relapsing multiple sclerosis (MS). The study population consists of two cohorts: patients newly initiating cladribine tablets (cladribine cohort) and patients newly initiating oral fingolimod tablets (comparator fingolimod cohort), with an aim to include 8000 patients (4000 patients per cohort). The study relies on secondary use of data from pre-existing MS registries/data sources (except in Germany, where primary data collection is performed). The study is projected to last 15 years, with an anticipated 5-year inclusion period. Study outcomes are: malignancies; severe infections; tuberculosis; progressive multifocal leukoencephalopathy; other opportunistic infections; herpes zoster; severe lymphopenia (Grade ≥ 3); and treatment discontinuation.

Results

As of 1 May 2021, 2393 patients were included in CLARION from seven participating MS registries/data sources (cladribine cohort, n = 1266; fingolimod cohort, n = 1127). The majority of patients are female (cladribine cohort, 72.5%; fingolimod cohort, 68.0%), with mean age at onset of MS of 31.5 years for the cladribine cohort and 30.9 years for the fingolimod cohort. The majority of patients in both cohorts had relapsing MS (cladribine cohort, 92.1%; fingolimod cohort, 93.5%).

Conclusion

By providing further information on adverse events of special interest during long-term follow-up, CLARION will assist neurologists and patients regarding treatment decision-making for management of relapsing MS.

Keywords:

• Multiple sclerosis
• cladribine tablets
• study design
• safety

Transparency

Declaration of funding

The CLARION study is sponsored by Merck [CrossRef Funder ID: 10.13039/100009945].

Declaration of financial/other relationships

HB’s institution (Monash University) received compensation for consulting, talks, and advisory/steering board activities from Alfred Health, Biogen, Merck, Novartis, and Sanofi; research support from Biogen, Merck, MS Research Australia, National Health and Medical Research (Australia), Novartis, the Oxford Health Policy Forum, and Roche. He has received personal compensation for steering group activities from Oxford Health Policy Forum and Merck. NM has consulted with Merck. AA is an employee of EMD Serono Research & Development Institute, Inc. Billerica, MA, USA (an affiliate of Merck KGaA). JS was an employee of IQVIA at the time of this study, and is currently an employee of CATO SMS, Durham, NC, USA. IB is an employee of IQVIA, a contract research organization that performs commissioned pharmacoepidemiological studies for several pharmaceutical companies. PK was an employee of IQVIA at the time of this study, and is currently an employee of REWODAT Oy, Lohja, Finland. MS is an employee of Merck Healthcare KGaA, Darmstadt, Germany. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Nicholas Moore, Aida Aydemir, Jaak Sõnajalg, Pasi Korhonen and Meritxell Sabidó were involved in the conception and design of the study whilst all authors were responsible for the analysis/interpretation of data, drafting and revision of the intellectual content and final approval of the paper.

Acknowledgements

Medical writing assistance (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Mark O’Connor and Joseph Ward of inScience Communications, Springer Healthcare Ltd, Chester, UK, and funded by Merck Healthcare KGaA, Darmstadt, Germany.

Data availability statement

Any requests for data by qualified scientific and medical researchers for legitimate research purposes will be subject to the Data Sharing Policy of Merck. All requests should be submitted in writing to the data sharing portal of Merck https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html. When Merck has a co-research, co-development, or co-marketing or co-promotion agreement, or when the product has been out-licensed, the responsibility for disclosure might be dependent on the agreement between parties. Under these circumstances, Merck will endeavour to gain agreement to share data in response to requests.