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NCT03961204

Long-Term Outcomes and Durability of Effect Following Treatment With Cladribine Tablets for MS (CLASSIC-MS)

Completed Phase 4 Results posted Last updated 31 October 2023
What this trial tests

Phase 4 trial testing Data Collection in Multiple Sclerosis (MS) in 662 participants. Completed in 13 May 2021.

Timeline
15 August 2019
Primary endpoint
27 February 2021
13 May 2021

Quick facts

Lead sponsorEMD Serono Research & Development Institute, Inc.
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeother
Enrollment662
Start date15 August 2019
Primary completion27 February 2021
Estimated completion13 May 2021
Sites99 locations across Italy, Finland, Poland, South Korea, Lebanon, Croatia, Tunisia, Russia

Drugs / interventions tested

Conditions studied

Sponsor

EMD Serono Research & Development Institute, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with Multiple Sclerosis (MS). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Using Wheelchair or Being Bedridden Assessed by Expanded Disability Status Scale (EDSS) Score 7.0 or Higher Primary · 3 months prior to study visit 1. Retrospectively from end of parent study (NCT00213135, NCT00641537 and NCT00725985) to study visit 1 (study visit 1 occurred up to 3 months from screening)

EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory \& cerebral functions, as well as walking ability. EDDS is a scale from 0-10 that evaluates a person with Multiple Sclerosis (MS) disability/neurologic function level where 0=normal and 10=death due to MS. Score of 7.0 is defined as unable to walk beyond approximately 5 meters even with aid, essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day. Score of 8.0 is defined as Essent

GroupValue95% CI
Cohort A8.26.2 – 10.6
Percentage of Participants With Expanded Disability Status Scale (EDSS) Score 6.0 or Higher Secondary · At study visit 1. Retrospectively after last IMP administration from parent study (NCT00213135, NCT00641537 and NCT00725985) to study visit 1 (study visit 1 occurred up to 3 months from screening)

EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory \& cerebral functions, as well as walking ability. EDDS is a scale from 0-10 that evaluates a person with MS disability/neurologic function level where 0= normal and 10= death due to MS. Score of 6.0 is defined as "intermittent or unilateral constant assistance (cane, crutch and brace) required to walk about 100 meters with or without resting".

GroupValue95% CI
Cohort A13.911.4 – 16.8
Clinical and Demographic Characteristic: Age, Disease Duration Secondary · At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

Clinical and demographic characteristics including age and disease duration is reported in the form of long term responders and non-responder. Here long term responder is defined as study participants not requiring disease modifying drug (DMD) 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.

Long-term responders: Age at study visit 1
GroupValue95% CI
Cohort A50.5± 10.65
Non-responders: Age at study visit 1
GroupValue95% CI
Cohort A47.1± 9.47
Long term responder: Disease duration
GroupValue95% CI
Cohort A19.82± 9.161
Non-responder: Disease duration
GroupValue95% CI
Cohort A16.82± 8.321
Number of Participants in Each Category of Clinical and Demographic Characteristics Secondary · At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

Clinical and demographic characteristics included gender, race, disease classification (relapsing remitting multiple sclerosis \[RRMS\], Secondary Progressive Multiple Sclerosis \[SPMS\], unknown \& no MS disease), Prior use of DMDs \& high-disease activity (HAD) status, education level and employment status. Number of participants in each category of clinical and demographic characteristics were reported in form of long term responders \& non-responder. Here long term responder is defined as participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-

Long term responder: Sex (Female)
GroupValue95% CI
Cohort A251
Non-responder: Sex (Female)
GroupValue95% CI
Cohort A171
Long-term responder: Sex (Male)
GroupValue95% CI
Cohort A127
Non-responder: Sex (Male)
GroupValue95% CI
Cohort A78
Long term responder: Race (White)
GroupValue95% CI
Cohort A368
Non-responder: Race (White)
GroupValue95% CI
Cohort A244
Long term responder: Race (Black or African American)
GroupValue95% CI
Cohort A1
Non-responder: Race (Black or African American)
GroupValue95% CI
Cohort A0
Clinical Characteristic: Expanded Disability Status Scale (EDSS) Score Secondary · At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory \& cerebral functions, as well as walking ability. EDSS scores range from 0.0 (normal) to 10.0 (dead). Clinical characteristics of EDSS score in form of long-term responders \& non-responder was reported for at parent study baseline (based on retrospective data collection \[based on chart review\] at study visit 1) \& study visit 1. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in pare

Long-term responders: EDSS score at parent study baseline
GroupValue95% CI
Cohort A2.44± 1.292
Non-responders: EDSS score at parent study baseline
GroupValue95% CI
Cohort A2.38± 1.251
Long term responder: EDSS score at study visit 1
GroupValue95% CI
Cohort A3.23± 2.121
Non-responder: EDSS score at study visit 1
GroupValue95% CI
Cohort A3.32± 2.102
Clinical Characteristic: Number of Relapses Secondary · At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

Relapse was defined as participant-reported symptoms \& objectively observed signs typical of an acute inflammatory demyelinating event in CNS, developing acutely or sub-acutely with duration of at least 24 hours, in absence of fever or infection. Clinical characteristics of number of relapses during last year before enrollment of parent study (it is reported based on retrospective data collection \[based on chart review\] at study visit 1) in the form of long-term responders \& non-responder was reported. Here long term responder is defined as study participants not requiring DMD 4 years or l

Long-term responders: number of relapses during last year before enrollment of parent study
GroupValue95% CI
Cohort A1.3± 0.64
Non-responders: number of relapses during last year before enrollment of parent study
GroupValue95% CI
Cohort A1.3± 0.56
Number of Total T1-weighted (T1-W) Lesions Secondary · At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

Total number of T1-W lesion were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.

Long-term responder
GroupValue95% CI
Cohort A12.7± 8.97
Non-responder
GroupValue95% CI
Cohort A16.1± 10.90
Number of Total T2-weighted (T2-W) Lesions Secondary · At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

Total number of T2-W lesion were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.

Long-term responder
GroupValue95% CI
Cohort A20.2± 18.67
Non-responder
GroupValue95% CI
Cohort A25.1± 18.17
T1-weighted (T1-W) Lesion Volume Secondary · At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

T1-W lesion volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.

Long-term responder
GroupValue95% CI
Cohort A1.655± 1.3953
Non-responder
GroupValue95% CI
Cohort A6.773± 6.4788
T2-weighted (T2-W) Lesion Volume Secondary · At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

T2-W lesion volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.

Long-term responder
GroupValue95% CI
Cohort A4.920± 6.7665
Non-responder
GroupValue95% CI
Cohort A14.664± 13.8109
Total Brain Volume Secondary · At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

Brain volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.

Long-term responder
GroupValue95% CI
Cohort A1472.559± 59.9500
Non-responder
GroupValue95% CI
Cohort A1417.431± 109.8668

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to study visit 2 (Up to approximately 6 months and Retrospective AEs data collection based on chart review of participants from end of parent studies; NCT00213135, NCT00641537 and NCT00725985). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A
Serious: 1/662 (0%)
Deaths: 0/662

Serious adverse events (1 terms)

ReactionSystemCohort A
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (7 terms — click to expand)

ReactionSystemCohort A
LymphopeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
NasopharyngitisInfections and infestations
Autoimmune thyroid disorderEndocrine disorders
Hepatic enzyme increasedInvestigations
FlushingVascular disorders

Most-reported serious reactions: Prostate cancer.

Data from ClinicalTrials.gov NCT03961204 adverse events section.

Sponsor's own description

The objective of this study was to collect data both retrospectively and prospectively in order to evaluate the long-term outcomes, durability of effect, and real-world treatment patterns following treatment with Cladribine Tablets or placebo in participants with multiple sclerosis (MS) who were previously participated in the parent studies (ORACLE MS and CLARITY/CLARITY-EXT).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician's Review.
    Giovannoni G, Mathews J. · · 2022 · cited 43× · PMID 35318617 · DOI 10.1007/s40120-022-00339-7
  2. Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension cohort of CLASSIC-MS: An ambispective study.
    Giovannoni G, Boyko A, Correale J, Edan G, et al · · 2023 · cited 27× · PMID 37012898 · DOI 10.1177/13524585231161494
  3. The assessment of efficient representation of drug features using deep learning for drug repositioning.
    Moridi M, Ghadirinia M, Sharifi-Zarchi A, Zare-Mirakabad F. · · 2019 · cited 8× · PMID 31726977 · DOI 10.1186/s12859-019-3165-y
  4. Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis.
    Allen-Philbey K, De Trane S, MacDougall A, Adams A, et al · · 2023 · cited 6× · PMID 37954917 · DOI 10.1177/17562864231200627
  5. Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.
    Guo X, Liu H, Song YJ, Wang JH, et al · · 2026 · cited 2× · PMID 41583906 · DOI 10.1002/mco2.70497
  6. Cladribine Use in Relapsing Multiple Sclerosis After 8-10 Years: Two Case Reports of Patients From the ORACLE-MS Study.
    Hernandez MA, Abreu Rodriguez R, Contreras Martin Y. · · 2024 · cited 1× · PMID 39735079 · DOI 10.7759/cureus.74671

Verify or expand the search:

Other trials of Data Collection

Trials testing the same drug.

Other recruiting trials for Multiple Sclerosis (MS)

Currently open trials in the same condition.

Other EMD Serono Research & Development Institute, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03961204.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing