Cladribine Tablets for Multiple Sclerosis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Keith Edwards, M.D.
No Placebo Group
Prior Safety Data
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to explore the concept that biomarker sensitivity will detect activity in Multiple Sclerosis (MS) subjects and allow appropriate change in treatment to prevent dysfunction.
Will I have to stop taking my current medications?
The trial requires that certain medications be stopped before participation. Specifically, treatments like ocrelizumab, rituximab, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, interferon, glatiramer acetate, and systemic corticosteroids must be stopped for specified periods before the trial. However, medications for spasticity or neuropathic pain can be continued if they have been stable for at least 30 days before screening.
What makes the drug Cladribine Tablets unique for treating multiple sclerosis?
Cladribine Tablets are unique because they are taken orally and work by selectively targeting and reducing certain immune cells, which helps manage multiple sclerosis. This is different from many other treatments that require injections or infusions.
12345What data supports the effectiveness of the drug Cladribine Tablets for treating multiple sclerosis?
Research shows that Cladribine Tablets, marketed as Mavenclad, are effective in treating relapsing multiple sclerosis, with studies indicating that 75% of patients experienced benefits for up to 4 years with a specific dosing schedule.
6791012Eligibility Criteria
This trial is for adults aged 21-65 with clinically definite Secondary Progressive Multiple Sclerosis (SPMS) who are neurologically stable and have chosen Cladribine Tablets as their treatment. Participants must be healthy otherwise, not pregnant or breastfeeding, agree to use effective contraception, and commit to follow-ups for two years post-study.Inclusion Criteria
I am between 21 and 65 years old.
I have been diagnosed with secondary progressive multiple sclerosis.
I have chosen cladribine tablets as my treatment and signed the consent form.
My disability score is between 2.0 and 7.0.
I am between 21 and 65 years old.
Exclusion Criteria
My kidney function is moderately to severely impaired.
I cannot have a lumbar puncture due to health risks.
I don't have any health conditions that the FDA says should not be treated with this drug.
I have or had severe diabetes, obesity, anorexia, high blood pressure, or high cholesterol.
I am not pregnant, planning to become pregnant, or breastfeeding during the study and for 6 months after.
I have a type of multiple sclerosis that is not primary progressive.
I have never been treated with cladribine.
Participant Groups
The study tests if biomarkers can detect MS activity in patients taking Cladribine Tablets, potentially guiding treatment changes to prevent dysfunction. It involves routine clinic visits and assessments over a two-year period following FDA guidelines.
1Treatment groups
Experimental Treatment
Group I: Cladribine TabletsExperimental Treatment1 Intervention
All participants will receive cladribine tablets according to the current United States Federal Food and Drug Administration (FDA) package guidelines.
Cladribine Tablets is already approved in European Union, United States, Australia, United States for the following indications:
🇪🇺 Approved in European Union as Mavenclad for:
- Relapsing-remitting multiple sclerosis
🇺🇸 Approved in United States as Mavenclad for:
- Relapsing forms of multiple sclerosis, including relapsing-remitting disease and active secondary progressive disease
🇦🇺 Approved in Australia as Mavenclad for:
- Relapsing-remitting multiple sclerosis
🇺🇸 Approved in United States as Leustatin for:
- Hairy cell leukemia
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Multiple Sclerosis Center of Northeastern New York, P.C.Latham, NY
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Who is running the clinical trial?
Keith Edwards, M.D.Lead Sponsor
EMD SeronoIndustry Sponsor
References
Marked inhibitory activity of masked aryloxy aminoacyl phosphoramidate derivatives of dideoxynucleoside analogues against visna virus infection. [2019]Lipophilic masked aryloxyaminoacylphosphoramidate derivatives of 2',3'-dideoxynucleoside (ddN) analogues with potent anti-HIV activity (i.e., stavudine [d4T], azidothymidine [AZT], dideoxycytidine [ddC], 3'thio-2',3'-dideoxy cytidine [3TC], dideoxyadenosine [ddA], and 2',3'-didehydro-2',3'-dideoxyadenosine [d4A]) activity were evaluated for their activity against visna virus (VV) in sheep choroid plexus (SCP) cells. The activity of several prodrug derivatives against VV proved markedly superior to that of the corresponding free ddN analogues. In particular, the d4A and ddA prodrug derivatives were exquisitely inhibitory in this model system (50% effective concentration [EC50],
Synthesis and anti-HIV activity of some novel chain-extended phosphoramidate derivatives of d4T (stavudine): esterase hydrolysis as a rapid predictive test for antiviral potency. [2017]Novel chain-extended nucleoside phosphoramidates of the anti-human immunodeficiency virus (HIV) drug d4T (stavudine) have been prepared as possible membrane-permeable prodrugs of the bio-active free 5'-monophosphates. Phosphorochloridate chemistry gave the target compounds in moderate to high yields, and all materials were fully characterized by spectroscopic and analytical methods. The compounds are related to the previously reported phenyl methoxyalaninyl derivative of d4T, which was shown to be a potent and selective inhibitor of HIV. In this study the amino acid nitrogen and ester moieties were separated by methylene spacers of between two and six carbon atoms. In vitro evaluation of these compounds indicated an almost complete lack of anti-HIV activity, the compounds being several orders of magnitude less potent than the corresponding alpha-amino acid derivatives. The reasons for the virtual lack of anti-HIV activity appear to involve poor enzyme-mediated hydrolysis.
Stavudine: A Review. [2019]Stavudine was the fourth nucleoside analog to be approved in the United States for the management of HIV-1 infections. It is a dideoxy analog of thymidine and is structurally similar to zidovudine. In adults, the usual dose is 40mg twice daily and probably does not have to be altered based on body weight unless the patient shows signs of toxicity from the drug, or has renal insufficiency. Clinical studies indicate that is very well tolerated, and, hematological toxicity is infrequent. Its dose limiting adverse effect is peripheral neuropathy, which is reversible in most cases with dose reduction or discontinuation. It has been shown to have synergistic activity against HIV-1 in vitro when combined with didanosine, lamivudine, nevirapine, and saquinavir. During clinical trials it has been shown that stavudine in combination with other antiviral drugs can reduce the viral load to 2 log(10) copies/ml. Recently it has been observed that Stavudine may have an increased side-effect profile and reduced efficacy when combined with zidovudine, and, therefore, is best used as an alternative to zidovudine in combination drug regimens.
Systematic review of clinical trials evaluating low doses of stavudine as part of antiretroviral treatment. [2019]Stavudine is a nucleoside analogue used for the treatment of HIV-1 infection, as part of highly active antiretroviral treatment. In developing countries, stavudine is used widely, owing to low cost and inclusion in generic fixed-dose combinations. In developed countries, stavudine is now rarely used, although it is highly effective. This is because newer drugs show lower rates of mitochondrial toxicities, such as lipoatrophy, peripheral neuropathy and lactic acidosis. In the development of stavudine, there was evidence that a dosage of 20-30 mg b.i.d. was effective, but the 40-mg b.i.d. dose gained regulatory approval. This review analyses the clinical trials conducted before and after the regulatory approval of stavudine, and shows that the dose of 30 mg b.i.d. has equivalent antiviral efficacy (given the caveats of meta-analysis), with some evidence of lower rates of peripheral neuropathy and lipoatrophy. With limited resources for HIV-1 treatment in developing countries, and only 25% of eligible patients receiving highly active antiretroviral treatment, low-cost treatment options such as stavudine still need to be pursued, if safety can be improved by dose optimisation.
A single-dose, randomized, open-label, two-period crossover bioequivalence study comparing a fixed-dose pediatric combination of lamivudine and stavudine tablet for oral suspension with individual liquid formulations in healthy adult male volunteers. [2013]Lamivudine (CAS 134678-17-4) is a synthetic nucleoside analogue with activity against HIV-1 and HBV. Stavudine (CAS 3056-17-5) is a synthetic thymidine nucleoside analogue, active against the human immunodeficiency virus (HIV). Lamivudine and stavudine in combination with other antiretroviral (ARV) agents are indicated for the treatment of HIV infection. As there are no suitable pediatric ARVs, adult fixed-dose ARVs are commonly used in children. This practice poses concerns about dose inaccuracy, which may lead to resistance or toxicity. A new fixed-dose combination (FDC) tablet for oral suspension, containing lamivudine 40 mg and stavudine 10 mg has been developed. An open-label, balanced, randomised, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study was conducted following administration of a fixed-dose combination of lamivudine and stavudine tablet for oral suspension (test formulation) and innovator products (reference formulations) in healthy, adult, male human subjects under fasting condition. Multiple blood samples were collected up to 36 h post dose. Plasma concentrations of lamivudine and stavudine were assayed using validated high-performance liquid chromatography with mass spectrometry analytical method. Pharmacokinetic parameters were calculated using non-compartmental analysis and bioequivalence was assessed using a mixed effect ANOVA model. The ratio of the least-square means (FDC to individual products) and 90% confidence intervals (CIs) of AUC(0-t), AUC(0-infinity) and C(max) for lamivudine and stavudine were all within 80.00-125.00%, suggesting a similar rate and extent of ARVs exposure in the bloodstream. The FDC and individual products were equally safe and well tolerated. The current FDC of lamivudine and stavudine is expected to provide a similar efficacy/safety profile as co-administration of the individual products, a better adherence to treatment, and considerable cost savings in the treatment of HIV in children.
A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. [2022]Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.
Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. [2022]Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy.
Long-term safety data from the cladribine tablets clinical development program in multiple sclerosis. [2022]Long-term safety data are of particular interest for any newly approved treatment in multiple sclerosis such as cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg), which is approved in Europe and the USA. Here we provide the final report on the integrated analysis of the safety profile of cladribine tablets 3.5 mg/kg from the clinical development program, including final data from the PREMIERE registry.
Efficacy of Cladribine Tablets as a Treatment for People With Multiple Sclerosis: Protocol for the CLOBAS Study (Cladribine, a Multicenter, Long-term Efficacy and Biomarker Australian Study). [2021]Cladribine tablets (marketed as Mavenclad) are a new oral therapy, which has recently been listed on the pharmaceutical benefits scheme in Australia for the treatment of relapsing multiple sclerosis (MS). The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS for up to 4 years in 75% of patients (based on annualized relapse rate). However, the reinitiation of therapy after year 4 has not been studied.
Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients. [2022]Label="OBJECTIVE" NlmCategory="OBJECTIVE">To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients.
A plain language summary of the impact of vaccines against flu and chickenpox in people with multiple sclerosis treated with cladribine tablets. [2023]Label="WHAT IS THIS SUMMARY ABOUT?">This is a summary of an article originally published in the Multiple Sclerosis Journal. Cladribine tablets (MAVENCLAD®) are an oral (taken by mouth) medication, approved for the treatment of people with relapsing forms of multiple sclerosis (MS, with episodes of new or worsening symptoms). They are administered for a maximum of 10 days per year, over a period of 2 years. Cladribine tablets work by temporarily reducing the number of lymphocytes, which are immune cells that help to fight off infections. Because of this, people with MS (also called PwMS) may have concerns about the effect of cladribine tablets on vaccines, as these work via immune cells to build protection against infection.
Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers. [2023]Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS).