Long term monitoring of multiple sclerosis patients on cladribine treatment
Cladribine: a multicenter, LOng-term efficacy and Biomarker Australian Study in patients with relapsing-remitting multiple sclerosis.
John Hunter Hospital of Hunter New England Local Health District
150 participants
Mar 14, 2019
Interventional
Conditions
Summary
Multiple sclerosis (MS) is the most common non-traumatic neurological disorder that affects young adults. Cladribine tablets (Mavenclad®) is a new oral therapy for MS. The current dosing for cladribine tablets is 2 courses given one year apart. This has been shown to be effective in reducing relapses in 75% of patients for up to 4 years (based on annualised relapse rate). However, re-initiation of treatment after year 4 has not been studied. This will be a multicenter, 6-year, phase IV, low interventional trial. Subjects meeting the eligibility criteria will receive an initial treatment course in year 1 and a continuing treatment course in year 2. After 3 years, patients will have the option for re-initiation of treatment, if clinically indicated or the option to switch to another disease modifying therapy (DMT). This study is testing the hypothesis that patients who receive an additional course of cladribine tablets will experience less disease activity than those who chose to change DMT. During the study we will evaluate blood-based molecules called biomarkers, brain scans and brain function tests. At the end of the study, we will use the results of these tests to determine if there are ways to decide if re-initiation of treatment after the initial 2-year course is appropriate. This may be one test or a combination of several tests. In addition, we determine if these biomarkers can be used at onset of disease to determine if patients will respond to cladribine therapy before they start.
Eligibility
Inclusion Criteria9
- To be eligible for inclusion into this study, the subjects must fulfill all of the following criteria:
- Subjects must be eligible for and already intending to commence cladribine tablets in accordance with the Australian PI.
- Subjects must have the ability to understand the purpose and risks of the study, as outlined in the Patient Informed Consent Form (PICF) and provide signed and informed consent and authorization to use protected health information (PHI) in accordance with nation and local privacy regulations.
- Subjects must meet the McDonald criteria (2017) for the diagnosis of RRMS.
- Male or female subjects aged 18-70 years old
- Be able to provide details for or consent to providing access to a stored minimum dataset (ie demographics, date of diagnosis, relapse information, baseline EDSS)
- Be able and willing to comply with all study procedures, including MRI scanning as per protocol.
- Must agree to use contraception from baseline until 6 months after the last dose of cladribine tablets, unless their partners are infertile or surgically sterile.
- Subjects must be aware of all precautions listed in the PI for Mavenclad® and any subsequent DMD treatment received within this clinical study must be adhered to
Exclusion Criteria11
- To be eligible for inclusion in this study the subjects must not meet any of the following criteria:
- Subjects must not have a concurrent diagnosis of a neurological, psychiatric or other disease which, in the opinion of the investigator, could impair capacity to provide informed consent, interfere with study assessments or impair the participant’s ability to comply with the study protocol.
- Any contra-indication to MRI scanning including:
- Cardiac pacemaker
- Cardiac defibrillator
- Metal fragments in the eye
- Any other non-MRI compatible medical device / implant or medical condition
- Severe claustrophobia
- Subjects who have any contraindication listed on the Australian PI or who have any of the listed precautions listed on the Australian PI.
- Patients who have highly active MS (defined as one relapse in the previous year and at least 1 T1Gd+ lesion or 9 or more T2 lesions, while on therapy with other DMTs. Two or more relapses in the previous year, whether on DMT treatment or not), who also have an EDSS of less than or equal to 5.0) and have not had prior exposure to drugs such as fingolimod, natalizumab, alemtuzumab, mitoxantrone and ocrelizumab.
- The Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the trial.
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Interventions
The standard dose of cladribine is 3.5mg/kg body weight over 2 years, administered as 1 treatment course of 1.75mg/kg per year. Each treatment course normally consists of 2 treatment weeks, one at the beginning of the first month followed by another one 4 weeks later. Each treatment week consists of 4-5 days in which a subject receives 10 or 20 mg as a single daily dose, depending on body weight as per PBS approved dosing. After 24 months, if there is evidence of disease activity (either clinical relapse or MRI activity) the patient will be offered either a third course of treatment (1.75mg/kg body weight, taken as 2 treatment weeks, 4 weeks apart), a switch in treatment, or no change. Further to this, at time points baseline, 3, 7, 12, 18, 24, 36, 48, 60, 72 months and the disease activity time point (clinical deterioration - either relapse or MRI activity) bloods will be taken to assess blood based biomarkers such as Neurofilament light chain levels and lymphocyte proportions. These will be assessed at the end of the study to determine 1) if there are biomarkers for treatment efficacy and 2) if there are biomarkers that indicate the need for a third course.
Locations(9)
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ACTRN12619000257167