Efficacy and Safety Study Comparing CPL409116 to Placebo in Participants With Active Rheumatoid Arthritis

NCT05374785 | Completed Phase 2

• 1 other identifier: 03JAK2021
• Study Type: interventional
• Target: 106
• Locations: 2 countries
• Sites: 10

Brief Summary

The purpose of the following phase II clinical trial is to determine safety and effectiveness of Janus kinases and Rho-kinases inhibitor (JAK/ROCKi) in patients with Rheumatoid arthritis after oral administration of investigational medicinal product (IMP) called CPL409116. JAK inhibitors are a new class of small molecule drugs that modulate inflammatory pathways by blocking one or more JAK receptors. In recent years, JAK inhibitors have emerged as a new option for the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, skin disorders and others. CPL409116 inhibits JAK1 and JAK3 with less inhibitory activity against JAK2 and Tyk2. Inhibition of these kinases decreases inflammatory cytokine release which in turn decreases lymphocyte activation and proliferation. Moreover, CPL409116 blocks Rho-kinases (ROCKs), which are involved in diverse cellular processes including actin cytoskeleton organization, cell adhesion and motility, proliferation, apoptosis as well as smooth muscle contraction. ROCKs signalling is one of the major pathways implicated in the pathogenesis of cardiovascular, renal as well as fibrotic diseases. However recent data indicate their role in immune cell regulation and inflammatory disease development. CPL409116 was designed predominantly for the therapy of immune-related diseases: rheumatoid arthritis (RA) or psoriasis but the unique mode of action of this compound may be beneficial for patients suffering from fibrotic complications developing on the basis of autoimmune diseases. RA is a chronic systemic autoimmune disease characterised by persistent joint inflammation leading to loss of joint function as well as cartilage and bone damage. Chronic, progressive course of the disease results in disability, reduced quality of life, as well as higher comorbidity and mortality rates. It is well documented that JAK kinases play a pivotal role in cytokine receptor signalling to phosphorylate and activate signal transducer and activator of transcription (STAT) proteins. Several of these JAK-controlled cytokine receptor pathways are immediately involved in the initiation and progression of RA pathogenesis. After preclinical studies conducted by Celon Pharma, CPL409116 could have been classified as a good clinical candidate for the treatment of patients with RA and next, results obtained after the phase I clinical trial in healthy volunteers confirmed its safety and a good pharmacokinetic profile.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; JAK inhibitors; Phase II

Outcome Measures

Primary Outcomes (1)

• Change in Disease Activity Score 28 joint count C reactive protein (DAS28(CRP)).

  Change from baseline in Disease Activity Score 28 joint count C reactive protein (DAS28(CRP)) score at Week 12 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28- (CRP) will be calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, CRP \[mg/L\] and patient global assessment of disease activity on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Score interpretation: \<2.6 suggests disease remission. 2.6-3.2 suggests low disease activity \>3.2-5.1 suggests moderate disease activity \>5.1 suggest high disease activity

  Baseline to Week 12

Secondary Outcomes (21)

• Proportion of patients with remission over time assessed by Disease Activity Score 28 joint count C reactive protein (DAS28(CRP)).

  Baseline through Week 12

• Proportion of patients achieving American College of Rheumatology (ACR) ACR20/50/70/90 response over time

  Baseline through Week 12

• Change in the Tender/Painful and Swollen Joint Count

  Baseline through Week 12

• Change in the Physician's Global Assessment (PhGA) of Arthritis

  Baseline through Week 12

• Incidence and severity of adverse events, serious adverse events, and withdrawals due to adverse events

  Baseline through Week 16

Other Outcomes (1)

• MFI (median fluorescence intensity) or percentage of phosphorylated proteins

  on Day 1; 29; 57 and 85

Study Arms (4)

CPL409116 60mg

EXPERIMENTAL

60 mg BID of CPL409116

Drug: CPL409116

CPL409116 120mg

EXPERIMENTAL

120 mg BID of CPL409116

Drug: CPL409116

CPL409116 240mg

EXPERIMENTAL

240 mg BID of CPL409116

Drug: CPL409116

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

CPL409116 DRUG

CPL409116 contained in the tablet called PG242 (60 mg)

CPL409116 120mg; CPL409116 240mg; CPL409116 60mg

Placebo OTHER

Tablets without CPL409116 as an active substance

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75 years at the time of signing informed consent;
• Meets ACR/EULAR 2010 RA Classification Criteria with a duration of RA disease of ≥6 months at time of screening and participant not diagnosed before 16 years of age;
• Must have active disease at both screening and baseline, as defined by having all three listed below:
• ≥ 6/68 tender/painful joints (TJC);
• ≥ 6/66 swollen joints (SJC);
• DAS28\> 3,2.
• NOTE: If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC for enrolment purposes.
• Must have a C-reactive protein (CRP) measurement ≥7 mg/L at screening;
• Must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA;
• Must have inadequate response, despite currently taking Methotrexate (MTX): weekly 15-25 mg oral or injected (subcutaneous or intramuscular) for at least 12 weeks prior to Screening, and with no change in dosage and route of administration for at least 8 weeks prior to Day 1/ baseline. A lower dose of ≥10 mg/week is acceptable if reduced for reasons of side effects or intolerance to MTX, e.g. nausea/vomiting, hepatic or hematologic toxicity (there must be clear documentation in the medical record);
• If using oral GCS must be on stable dose (equivalent to ≤10mg/day of prednisone) for at least 4 weeks prior to Day 1/ baseline;
• If using NSAIDs must be on stable dose for at least 4 weeks prior to Day 1/ baseline;
• A woman must be either:
• Not of childbearing potential:
• postmenopausal (\>45 years of age with amenorrhea for at least 12 months, without using exogenous hormonal contraception and with FSH ≥ 40 IU/L);

You may not qualify if:

• Has had a serious infection (e.g. sepsis, pneumonia, pyelonephritis or any other serious infection as per Investigator's judgement), or has been hospitalized or received intravenous antibiotics for an infection within 3 months prior to Day 1/ baseline;
• Any active infection including localized infections within 2 weeks prior to baseline;
• History of opportunistic or recurrent (3 or more of the same infection requiring anti-infective treatment in any rolling 12-month period) infection;
• History of chronic infections requiring anti-infective treatment within 6 months prior to Screening;
• Subjects with a high risk of infection in the Investigator's opinion (e.g. subjects with leg ulcers, indwelling urinary catheter);
• History of infected joint prosthesis or other implanted device with the retention of prosthesis or device in situ;
• Symptomatic herpes zoster within 3 months prior to Screening;
• History of disseminated herpes simplex infection or disseminated/complicated herpes zoster;
• Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency;
• Known infection with human immunodeficiency virus (HIV) or positive test at Screening;
• Presence of any of the following laboratory abnormalities at Screening:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥1.5 x the upper limit of normal (ULN);
• Absolute neutrophil count of \<1.5 x 10\^9/L (\<1500/mm\^3);
• Absolute lymphocyte count of \<0.75 x 10\^9/L (\<750/mm\^3);
• Absolute white blood cell (WBC) count of \< 3.0 x 10\^9 /L (\<3000/mm\^3);

Sponsors & Collaborators

• Celon Pharma SA: lead
• National Center for Research and Development, Poland: collaborator

Study Sites (10)

MICS Centrum Medyczne Bydgoszcz

Bydgoszcz, 85-065, Poland

Location

Centrum Nowoczesnych Terapii Sp. z o.o. "Dobry Lekarz"

Krakow, 31-011, Poland

Location

AMICARE Centrum Medyczne Sp. z o. o., Spółka Komandytowa

Lodz, 90-644, Poland

Location

Medyczne Centrum Hetmańska

Poznan, 60-218, Poland

Location

Samodzielny Publiczny Zespół Opieki Zdrowotnej w Tomaszowie Lubelskim

Tomaszów Lubelski, 22-600, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, 04-141, Poland

Location

PCS Sp. z o. o.

Łady, 05-090, Poland

Location

Medical center of the limited liability company "Medical center "Consilium Medical"

Kyiv, 04050, Ukraine

Location

Polyclinic of the center of medical services and rehabilitation JSC "Company of aviation and rocket technology manufacture"

Kyiv, 04050, Ukraine

Location

Communal enterprise "Hospital No. 1" of the Zhytomyr City Council, consulting and treatment department "Research Center"

Zhytomyr, 10002, Ukraine

Location

Related Publications (1)

• Wieczorek M, Kisiel B, Wlodarczyk D, Leszczynski P, Kurylchyk IV, Vyshnyvetskyy I, Kierzkowska I, Pankiewicz P, Kaza M, Banach M, Kogut J. Dual JAK and ROCK inhibition with CPL'116 in patients with rheumatoid arthritis with inadequate response to methotrexate: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Rheumatol. 2025 Sep;7(9):e629-e641. doi: 10.1016/S2665-9913(25)00060-8. Epub 2025 Jun 11.

  PMID: 40516565 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: In all treatment arms the investigated product/ placebo is to be administered orally in a blinded fashion. In order to maintain the blind and minimize bias, all subjects will receive the same number and types of tablets each day of treatment (4 tablets BID)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 16, 2022
• Study Start: May 1, 2022
• Primary Completion: May 27, 2024
• Study Completion: May 27, 2024
• Last Updated: January 23, 2025

Record last verified: 2025-01

Locations

UA (3); PL (7)