Evaluating the Long-Term Outcomes and Durability of Effect Following Treatment with Cladribine Tablets for Multiple Sclerosis: An Exploratory Phase IV Ambispective Study of Patients Who Previously Participated in the CLARITY/CLARITY-EXT and ORACLE MS Clinical Trials

• Register: EUCTR
• Last refreshed on: 8 November 2021
• Main ID: EUCTR2019-000069-19-PL
• Date of registration: 27/06/2019
• Prospective Registration: Yes
• Primary sponsor: Merck KGaA
• Public title: Evaluating the Long-Term Outcomes and Durability of Effect Following Treatment with Cladribine Tablets for Multiple Sclerosis: An Exploratory Phase IV Ambispective Study of Patients Who Previously Participated in the CLARITY/CLARITY-EXT and ORACLE MS Clinical Trials
• Scientific title: Evaluating the Long-Term Outcomes and Durability of Effect Following Treatment with Cladribine Tablets for Multiple Sclerosis: An Exploratory Phase IV Ambispective Study of Patients Who Previously Participated in the CLARITY/CLARITY-EXT and ORACLE MS Clinical Trials - CLASSIC-MS
• Date of first enrolment: 08/09/2019
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000069-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Ambispective; data from patients participating to past trials. No IMP treatment during this study; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Estonia, Finland, France, Georgia, Germany, Greece, Italy, Korea, Republic of, Latvia, Lebanon, Lithuania, Morocco, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Sweden, Switzerland, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

Key inclusion & exclusion criteria

Inclusion criteria:
For Main Study and MRI Sub-Study:
1. Patients with MS randomised in CLARITY/CLARITY-EXT clinical trial(s) who have received = 1 course of IMP (Cladribine Tablets or placebo).
or
Patients with their FCDE randomised in ORACLE MS clinical trial who have received
= 1 course of IMP (Cladribine Tablets or placebo).
2. Patients can give signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and this protocol.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 920
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 80

Exclusion criteria:
Main study:
Any condition, including any uncontrolled disease state other than MS, that in the Investigator’s
opinion, constitutes an inappropriate risk or a contraindication for participation in the study or that
could interfere with the study objectives, conduct, or evaluation.
MRI-Substudy:
a. Female study participants who are pregnant
b. Patient is taking Cladribine Tablets as part of another study at the time of the start of
this study (i.e. patients participating in a clinical trial or observational study but do not
receive Cladribine Tablets as part of these studies are allowed to participate in the substudy).




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Multiple Sclerosis
MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: MAVENCLAD
Product Name: Cladribine tablets
Product Code: Not applicable
Pharmaceutical Form: Tablet

Primary Outcome(s)

Primary end point(s): Proportion of study participants using a wheelchair (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) the majority of the time in the 3 month prior to Study Visit 1 for the CLARITY/CLARITY-EXT and ORACLE MS populations, determined via:
• Expanded Disability Status Scale (EDSS)
score of 7.0 or higher (if available), or
• Alternative clinical description data in medical records.

Main Objective: To evaluate long-term mobility after treatment with an investigational medicinal product (IMP; Cladribine
Tablets or placebo) as part of the Phase III ORACLE MS and CLARITY/CLARITY-EXT clinical trials.

Secondary Objective: 1. To assess the long-term disability status after treatment with IMP as part of the Phase III ORACLE MS and CLARITY/CLARITY-EXT clinical trials for the CLARITY/CLARITY-EXT and ORACLE MS populations.
2. To evaluate differences in clinical characteristics between long-term responders and study participants
requiring alternate therapies following treatment with IMP for the CLARITY/CLARITY-EXT and ORACLE
MS populations.
MRI Sub-Study:
3. To evaluate differences in magnetic resonance imaging (MRI) characteristics between long-term responders and study participants requiring alternate therapies following treatment with IMP for the
CLARITY/CLARITY-EXT and ORACLE MS populations.

Timepoint(s) of evaluation of this end point: Study visit 1

Secondary Outcome(s)

Secondary end point(s): 1. Proportion of study participants with 3-month sustained EDSS of 6.0 or higher in the last year prior to enrolment (i.e.ambulatory disability consistent with EDSS on at least 2 clinic visits no less than 3 months apart) as determined by EDSS documentation or corresponding clinical description in medical records for the CLARITY/CLARITY-EXT and ORACLE MS populations
2. Clinical characteristics of long-term responders (defined as study participants who did not demonstrate any evidence of disease reactivation based on Investigator assessment of clinical and imaging outcomes until Year 4 or later following their last dose of IMP and who did not receive disease modifying treatment until Year 4 or later following their last dose of IMP) compared to those of other study participants who started on alternate therapy less than 4 years following their last dose of IMP for the CLARITY/CLARITY-EXT and ORACLE MS populations.
MRI Sub-Study:
3. MRI characteristicsc at Study Visit 2 of longterm responders (defined as study participants who did not demonstrate any evidence of disease reactivation based on Investigator assessment of clinical and
imaging outcomes until Year 4 or later following their last dose of IMP and who did not receive disease modifying treatment until Year 4 or later following their last dose of IMP) compared to those of other study participants who started on alternate therapy less than 4 years following their last dose of IMP for the CLARITY/CLARITY-EXT and ORACLE MS populations.

Timepoint(s) of evaluation of this end point: ad 1. Study Visit 1
ad 2. Study Visit 1
ad 3. Study visit 2

Secondary ID(s)

2019-000069-19-CZ

MS700568_0026

Source(s) of Monetary Support

Merck KGaA

Ethics review

Status: Approved
Approval date: 19/06/2019
Contact: