Current report 11/2024 – Results of phase II clinical trial for CPL’ 116, a JAK/ROCK dual inhibitor in the treatment of Rheumatoid Arthritis (RA)

In reference to current reports 36/2021 on the successful completion of phase I clinical trial and 47/2021 on submission of an application for consent to commence a phase II trial of an innovative JAK/ROCK inhibitor – CPL 409116 – in the treatment of Rheumatoid Arthritis (RA), the Company’s Management Board hereby informs that on June 17, 2024 the Company has concluded an analysis of the phase II trial findings.

It was a multicentre, randomised, double-blind clinical trial conducted on over 100 patients who have had inadequate therapeutic response to methotrexate. The compound was administered over the course of 12 weeks in 3 doses of 60, 120 and 240 mg BID  as an add-on to methotrexate therapy. The trial was placebo-controlled. The objective of the trial was to determine the dose-dependent response to treatment. The primary endpoint was efficacy determined based on the change (compared to baseline) at week 12, measured as the Disease Activity Score-28 for RA with CRP. (DAS 28-CRP). Other, secondary endpoints included efficacy assessment measured using other scales, remission and safety of use.

Findings: CPL’116 improved the patients’ condition measured with DAS28-CRP in a dose-dependent manner. Change in the DAS28-CRP score in week 12 compared to baseline was 1.702; 2.032; 2.361 and 1.668 for doses of 60, 120, 240 mg and placebo, respectively. Change in the DAS28-CRP score compared to placebo (LS MD) was 0.145 (p=0.67); 0.564 (p=0.10), and 0.887 (p=0.01) for doses of 60, 120 and 240 mg, respectively. Hence the primary endpoint results are statistically significant, the primary endpoint is met.

The response to treatment in the 240 mg dose was fast – a statistically significant benefit over placebo with regard to the DAS28-CRP score was already observed at week 4 of treatment.

The difference of the 240 mg dose compared to placebo was statistically significant in most of the secondary endpoints. The high remission rate observed at this dose throughout the trial (defined as DAS28-CRP<2.6) – which exceeded 45% – is particularly noteworthy.

The 120 mg dose was partially efficacious. Statistically significant differences compared to placebo were observed is some measurements and scales.

The overall tolerability of the compound was good and no unexpected adverse effects previously unknown for these drug classes have been observed.

In the upcoming weeks, the Company will present results of pharmacokinetic and pharmacodynamic analyses for this trial, as well as detailed safety parameter analyses.

The positive outcomes of this trial validate clinical development of CPL’116 as the world's first dual JAK/ROCK inhibitor in a broad spectrum of autoimmune diseases, in particular conditions with an inflammatory and fibrotic component, such as idiopathic pulmonary fibrosis (IPF) or rheumatoid arthritis-associated interstitial lung disease (RA-ILD).