Cladribine Tablets After Treatment With Natalizumab (CLADRINA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04178005|
Recruitment Status : Active, not recruiting
First Posted : November 26, 2019
Last Update Posted : October 4, 2022
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Drug: Cladribine||Phase 4|
This will be an open label, single arm, multicenter, collaborative phase 4 research study, designed to generate hypotheses regarding the transition to cladribine tablets after treatment with natalizumab in patients with relapsing forms of multiple sclerosis MS, to include relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS).
The total duration of this interventional study will be 2 years, but patients who require additional time (up to 6 months) for recovery of Absolute lymphocyte count (ALC) to 800 cells/ul prior to the second treatment course will be followed for up to 6 additional months in order to have a full second year of follow up after initiation of the second year's treatment course (for a total study duration of up to 30 months in some patients). A total of 40 study participants with relapsing forms of MS, to include RRMS and active SPMS, who meet the criteria for treatment with cladribine tablets as per the approved United States Prescribing Information (USPI) are planned to be enrolled at up to three centers in the United States. All study participants will receive treatment with cladribine 10 mg tablets during year 1 and year 2 according to the approved USPI (EMD Serono, 2019). Cladribine 10 mg tablets will be provided as commercial material. Treatment with cladribine tablets is intended to be initiated approximately 14 days after the last infusion of natalizumab (e.g., a 14-day "washout"), with a maximum permissible washout period of no more than four weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Cladribine Tablets After Treatment With Natalizumab (CLADRINA)|
|Actual Study Start Date :||February 19, 2020|
|Estimated Primary Completion Date :||August 30, 2024|
|Estimated Study Completion Date :||December 2024|
All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI.
Each treatment course is divided into 2 treatment cycles:
The cycle dosage will be administered as 1 or 2 cladribine 10 mg tablets daily over 4 or 5 consecutive days.
All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI
Other Name: Mavenclad
- Absolute and percent change of T cells, B cells, DC subset and NfL levels in blood. [ Time Frame: 24 months ]The absolute and percent change from baseline will be presented for each time point for CD3+ T lymphocytes, CD19+ B lymphocytes, CD11c+ DC subsets, NfL levels in blood, with a two-sided 95% CI and p value. As these data are not expected to be normally distributed, the nonparametric Wilcoxon signed rank test will be used to compare each biomarker at baseline and during treatment. Spearman rank correlations will be used to examine the relationship between biomarkers and clinical/safety endpoints.
- Annualized Relapse Rate (ARR) [ Time Frame: 12 months ]The ARR over the 12- and 24-month periods will be presented, accompanied by the respective 95% CIs. The proportion (and 95% CI) of participants experiencing a relapse over the 12 month and 24-month periods will also be presented.
- The Expanded Disability Status Scale : Neurological disability outcome [ Time Frame: 24 months ]
The Expanded Disability Status Scale (EDSS) will be utilized to measure the accumulation of neurological disability.
The change in EDSS from baseline will be reported at month 12 and month 24. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.
EDSS steps 1.0 to 4.5 refer to people with MS who are able to walk without any aid and is based on measures of impairment in eight functional systems (FS):
muscle weakness or difficulty moving limbs, ataxia, loss of balance, coordination or tremor, problems with speech, swallowing and nystagmus, numbness or loss of sensations, bowel and bladder function, problems with sight, problems with thinking and memory, other A functional system (FS) represents a network of neurons in the brain with responsibility for particular tasks. Each FS is scored on a scale of 0 (no disability) to 5 or 6 (more severe disability).
EDSS steps 5.0 to 9.5 are defined by the impairment to walking.
- Magnetic Resonance imaging (MRI) outcomes [ Time Frame: 24 months ]The mean number of new or new/ enlarging T2 lesions, and the number of gadolinium (Gd)-enhancing lesions.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04178005
|United States, Texas|
|UT Southwestern Medical center|
|Dallas, Texas, United States, 75390|
|Principal Investigator:||Olaf Stuve, MD, PhD||UT Southwestern Medical Center|