Phase 3 trial of oral cladribine for generalized MG doses first patient
Study will test if short courses better at easing symptom severity than placebo
The first patient has been dosed in a Phase 3 clinical trial that’s assessing the safety and efficacy of oral cladribine for treating generalized myasthenia gravis (gMG).
The study, called MyClad (NCT06463587), is intended to test whether short courses of cladribine treatment can outperform a placebo at easing gMG symptom severity. A total of 240 adult gMG patients recruited from the U.S., Japan, and South Korea are participating.
Cladribine capsules have the potential to become the first oral treatment for gMG, according to Merck Kgaa, the company developing the therapy.
“This treatment approach holds the promise of achieving a high degree of disease activity control, offering greatly improved convenience, and ultimately enabling patients to live their lives as normally as possible,” Jan Klatt, head of development unit neurology and immunology for the healthcare business of Merck, said in a company press release.
Myasthenia gravis (MG) occurs when the immune system mistakenly attacks proteins involved in nerve-muscle communication, leading to muscle weakness and fatigue. An important component of this attack is the production of harmful self-reactive antibodies driven by B-cells and T-cells, two types of immune cells. Cladribine targets and kills off the cells, reducing the antibodies that drive MG.
Merck Kgaa, known as Emd Serono in North America, markets a short-course oral tablet form of cladribine, known as Mavenclad, for relapsing forms of multiple sclerosis, another autoimmune disorder that affects the nervous system. Merck acquired the rights to develop cladribine as a possible gMG therapy at the end of 2021.
“Cladribine capsules have the potential to tackle the disease at the root course,” Klatt said in an email to Myasthenia Gravis News, adding “such an approach could allow for slowing the disease progression.”
A small study involving 13 patients with refractory, or difficult to treat, MG showed cladribine could ease symptoms and reduce the need for high-dosage corticosteroids.
Testing oral cladribine in gMG
The ongoing MyClad trial is divided into three periods. In the first period, known as the double-blind placebo control pivotal period, participants will be randomly assigned to two oral courses of either a low or high dose of cladribine, or a placebo, separated by four weeks.
This will be followed by a blinded extension period, wherein the participants first given a placebo will receive either a low or high dose of cladribine and vice versa, again in the form of two short courses separated by four weeks.
In the final period, participants requiring re-treatment with either a low or high dose of cladribine will be re-treated if the supplemental dose is deemed clinically justified. This period will last until the end of the trial at week 144, or slightly more than 2.5 years.
“The short course oral dosing scheme that can be taken at home with a very low number of capsules is very convenient and has the potential to increase adherence to treatment which is necessary for longer-term beneficial outcomes,” Klatt said.
The first period will let researchers assess the efficacy of the new oral cladribine formulation in treating gMG by evaluating changes in the scores of the MG Activities of Daily Living, a scale used to assess MG symptom severity, from the study’s start to week 24, or about six months. This will be the trial’s main goal.
The two other periods will let researchers evaluate if the therapy has sustained efficacy, requires re-treatment, and is safe long term. The pharmacological properties of the new formulation will also be assessed.
“Given our extensive experience in addressing patients’ needs in immune-driven neurological conditions, we believe that cladribine capsules represent a highly differentiated potential therapeutic option for gMG,” Klatt said.
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