Clinical trial NCT04756687: Real World Analysis on Lymphocyte Reconstitution After Lymphopenia in Participants Treated by Tecfidera
Official title: A Retrospective Analysis in Real World on Lymphocyte Reconstitution After Lymphopenia in Patients Treated by Tecfidera and Description of Management Strategies in France
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2021-02-16
Enrollment: 1507
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All RRMS participants treated with DMF who fulfil the inclusion criteria are eligible to participate in the study.

Brief summary: The primary objective of the study is to describe absolute lymphocyte count (ALC) reconstitution after Dimethyl fumarate (DMF) discontinuation, in Relapsing-Remitting Multiple Sclerosis (RRMS) participants with lymphopenia.

The secondary objectives of the study are characterization of lymphopenia in overall population; characterization of lymphopenia in participant with DMF discontinuation ; description of the evolution of ALC during DMF treatment; description of the time to reach a discontinuation of DMF treatment; exploration of the time to reach clinical outcomes (Expanded Disability Status Scale \[EDSS\] and relapse) according to lymphopenia; description of the event rate of the serious or opportunistic infections in overall population from DMF initiation and according to DMF discontinuation and lymphopenia; description of the event rate of serious and opportunistic infections in overall population from DMF initiation and according to lymphopenia; estimation of the associations between the baseline demographic and clinical characteristics and the risk to reach a lymphopenia; estimation of the associations between the baseline demographics and clinical characteristics and the risk to reach an ALC reconstitution after DMF discontinuation in participants with lymphopenia; and investigation of the changes of absolute cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) count in overall population on DMF if available.

Detailed description: The study will select participants initiating treatment from 01 Jan 2016 to 15 Dec 2020.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of RRMS at DMF initiation
* Minimum of 3 months of continuous treatment with DMF\*
* Initiation of DMF between January 1st, 2016 and December 15th, 2020
* Minimum of 2 ALC assessments:

  1. 1 ALC at DMF initiation (or within 6 months before DMF initiation); or under DMF treatment
  2. 1 ALC before the database extraction (15/06/2021).

     * to avoid the early DMF discontinuations for reasons other than lymphopenia.

Exclusion Criteria:

* Participants will be excluded from the study entry if they express their opposition to collect the data upon the information.

Primary outcomes:
measure: Time to ALC Reconstitution After DMF Discontinuation
timeFrame: Up to end of study (121 days)
Secondary outcomes:
measure: Time From DMF Initiation to Lymphopenia Initiation Assessed in Participants With and Without DMF Discontinuation
timeFrame: Up to end of study (121 days)
measure: Time From DMF Initiation to Lymphopenia Assessed at Time of DMF Discontinuation
timeFrame: Up to end of study (121 days)
measure: Percent Change in ALC Over Time From DMF Initiation to DMF Discontinuation or End of Study
timeFrame: Up to end of study (121 days)
measure: Time From DMF Initiation to DMF Discontinuation
timeFrame: Up to end of study (121 days)
measure: Percentage of Participants with Discontinuation of DMF Treatment
timeFrame: Up to end of study (121 days)
measure: Time to DMF Discontinuation to the First Relapses and/or an EDSS Progression
timeFrame: Up to end of study (121 days)
measure: Percentage of Participants With Serious or Opportunistic Infections in Overall and According to DMF On-going or not and in Lymphopenic Population
timeFrame: Up to end of study (121 days)
measure: Percentage of Participants With Serious and Opportunistic Infections in Overall and in Lymphopenic Population
timeFrame: Up to end of study (121 days)
measure: Time to Occurrence of Lymphopenia During DMF Treatment Assessed in Association Between Demographic and Clinical Characteristics
timeFrame: Up to end of study (121 days)
measure: Time to Lymphocyte Reconstitution After DMF Discontinuation Assessed in Association Between Demographic and Clinical Characteristics
timeFrame: Up to end of study (121 days)
measure: Percent Change from Baseline in Absolute CD4+ Count
timeFrame: Up to end of study (121 days)
measure: Percent Change from Baseline in Absolute CD8+ Count
timeFrame: Up to end of study (121 days)
measure: Percent Change from Baseline in Absolute CD4+/CD8+ Ratio
timeFrame: Up to end of study (121 days)
Other outcomes:
Locations:
city: Amiens
country: France
facility: Research Site
city: Besançon
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Clermont-Ferrand
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Grenoble
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Limoges
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nancy
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Nîmes
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Saint-Etienne
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Île-de-France - Bicêtre
country: France
facility: Research Site
city: Île-de-France - Créteil
country: France
facility: Research Site
city: Île-de-France - Poissy St-Germain
country: France
facility: Research Site
city: Île-de-France - Pontoise
country: France
facility: Research Site
city: Île-de-France - Rothschild
country: France
facility: Research Site
city: Île-de-France - Saint-Antoine
country: France
facility: Research Site
city: Île-de-France - Saint-Denis
country: France
facility: Research Site
city: Île-de-France - Salpêtrière
country: France
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: