Digital Therapeutic CT-132 Meets Primary End Point in Phase 3 Study of Preventive Migraine

Shaheen Lakhan, MD, PhD, FAAN

According to an announcement, CT-132 (Click Therapeutics), an investigational prescription digital therapeutic, met its primary end point in the phase 3 ReMMi-D randomized trial (NCT05853900) of patients with episodic migraine, with results revealing a significant reduction in monthly migraine days (MMDs) among treated patients over a 12-week treatment period.¹

ReMMi-D included 568 adults with migraine who were randomly assigned to CT-132 or sham digital control intervention for a 12-week treatment period. The study, a decentralized, double-blind study, enrolled patients on the most commonly prescribed acute and preventive migraine medications. CT-132 delivers a proprietary clinical intervention aimed at reducing brain hypersensitivity implicated in migraine by modulating patient responses to environmental and internal stimuli to help restore patients’ ability to engage fully in daily activities.

After 12 weeks of treatment, results revealed a statistically significant reduction in MMDs relative to sham (–0.9 MMDs; P = .005), with those on active treatment experiencing –3.04 MMDs by end of treatment. Treatment with CT-132 led to observed improvements in Migraine-Specific Quality-of-Life Questionnaire (MSQ) at weeks 8 and 12 (both P <.001 at all time points), with improvements seen as early as week 4. At the conclusion of the treatment period, investigators saw categorical enhancements in the Migraine Disability Questionnaire (MIDAS) among CT-132-treated patients.

"This is a significant milestone for more than one billion people worldwide living with migraine. Click has developed and evaluated a first-in-class digital migraine preventive therapeutic, CT-132, in two separate clinical studies to demonstrate a reduction in monthly migraine days, the gold standard measure,” Shaheen Lakhan, MD, PhD, FAAN, chief medical officer at Click Therapeutics, said in a statement.¹ "We look forward to advancing our FDA Breakthrough Designated asset through regulatory clearance and, if successful, offering a new therapeutic option that can be delivered to any eligible patient with a smartphone, meaningfully enhancing access to care."

ReMMi-D was comprised of those who have at least 1-year history of migraine consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd edition. Coming into the study, patients were managing migraines with at least 1 prescription acute treatment and/or prescription first or second-line preventive medications, as assessed by a physician. The study excluded those taking a prescription anti-calcitonin gene-related peptide (CGRP) for either episodic or chronic migraine.

In the trial, patients in both the intervention and sham groups demonstrated nearly 100% median completion of daily tasks. Within the CT-132 group, there was observed improvements in health, as measured by Patient Global Impression-Change at the end of the 12-week study (P <.001). Above all, the therapy was considered safe and well tolerated, with no treatment-related adverse events.

Stewart Tepper, MD

According to Click, data from its other phase 3 bridging study, ReMMiD-C (NCT06004388), provided supportive information to the pivotal study. ReMMiD-C, a fully remote and decentralized trial, comprised of 110 patients with migraine who were receiving CGRP inhibitor therapy, an emerging class of third line preventive medication. This randomized, double-blind, 12-week trial was used to complement clinical data from ReMMi-D in patients treated with first and second line preventive medications.²

"The design and results of these studies, which are similar to comparable preventive medication migraine trials, support the clinical performance of CT-132," Stewart Tepper, MD, vice president of the New England Institute for Neurology and Headache, said in a statement.¹ "The clinical data demonstrate a successful reduction in monthly migraine days, which was the primary endpoint, as well as improving quality of life and reducing disability. This is the first migraine digital therapeutic to be studied with this degree of rigor, and the availability of CT-132 would be a very useful addition to our migraine armamentarium providing additional benefit to patients on migraine medication and expanding access to non-pharmacological treatment options."

REFERENCES
1. Click Therapeutics Announces CT-132 Met Primary Endpoint for the Reduction of Monthly Migraine Days in ReMMi-D Pivotal Trial. News release. Click Therapeutics. September 4, 2024. Accessed September 6, 2024. https://www.businesswire.com/news/home/20240904512812/en/Click-Therapeutics-Announces-CT-132-Met-Primary-Endpoint-for-the-Reduction-of-Monthly-Migraine-Days-in-ReMMi-D-Pivotal-Trial
2. Click Therapeutics Launches Additional Randomized Clinical Study in Migraine, Conducted in Partnership with Syneos Health. August 2, 2023. Accessed September 6, 2024. https://www.biospace.com/click-therapeutics-launches-additional-randomized-clinical-study-in-migraine-conducted-in-partnership-with-syneos-health