Rheumatoid Arthritis MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Revolo Biotherapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A participant must meet the following criteria to be eligible for inclusion in the study: Demographic and Laboratory Assessments: 1. Participants are men or women ages = 18 and = 75 years. 2. Participant must have laboratory values meeting the criteria listed below within the screening period prior to the first dose of study drug. Outofrange laboratory parameters may be rechecked one time, after consultation with the sponsor or its designee, before the participant is considered a screen failure. a. Serum alanine transaminase (ALT) 3000/µL c. Absolute neutrophil count (ANC) > 1500/µL d. Platelet count > 100,000/µL e. Absolute lymphocyte count > 800/µL f. Hemoglobin > 10 g/dL 3. Participant must have a negative test result for hepatitis A virus immunoglobulin M (HAVIgM), hepatitis B surface antigen (HBsAg), HBcAb (participants who have been vaccinated against hepatitis B [HB] and are HBsAb positive may be enrolled), hepatitis C virus (HCV) antibody (if hepatitis C RNA level is undetectable at Screening, the participant can participate in this study), and human immunodeficiency virus (HIV) Ab at Screening. 4. Participant must have a negative tuberculosis (TB) test: QuantiFERON TB-Gold In-Tube test (or equivalent if compliant with local TB guidelines) or purified protein derivative (PPD). Participants who have previously received an adequate course of therapy as per local standard of care for latent TB do not require TB test. 5. Participant is able and willing to provide written informed consent and comply with the requirements of the study protocol. Diagnosis and Disease Activity: 6. Participant has a clinical diagnosis of RA for > 3 months based on the 1987 ACR classification criteria or 2010 ACR/European League against Rheumatism (EULAR) criteria. 7. Participant has moderately to severely active RA defined as: = 6 swollen joints (from a SJC66) and = 6 tender joints (from a TJC68) at both Screening and Baseline/Day 1. 8. Participant has a high-sensitivity C-reactive protein (hsCRP) = 3 mg/L at Screening. 9. Participant has an incomplete response to MTX. Participants must have been on oral or parenteral MTX therapy = 3 months and on a stable prescription of 15 to 25 mg/week (or = 10 mg/week in participants intolerant of methotrexate at doses = 15 mg/week) for = 4 weeks prior to the first dose of study drug. Participant must be expected to be able to continue on a stable dose of MTX for the duration of study participation. Dose adjustments are only permitted for the management of toxicity. 10. Prior treatment with additional conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is allowed; however, the participant must be on MTX only at Baseline/Day 1 and an appropriate washout needs to be satisfied, as specified in the protocol (Section 9.2) to be eligible for the study. 11. Participants must have discontinued all biologic DMARD (bDMARD) and targeted synthetic DMARD (tsDMARD) therapy prior to the first dose of study drug. The washout period of these agents prior to the first dose of study drug is specified below or should at least 5 times the mean terminal elimination half-life of a drug: a. = 4 weeks for etanercept, adalimumab, infliximab, certolizumab, golimumab, tocilizumab, and abatacept b. prior rituximab treatment is not allowed c. = 4 weeks for any tsDMARD (including but not limited to upadacitinib, tofacitinib, barici
Exclusion criteria
Exclusion criteria: A participant who meets any of the following criteria will be ineligible to participate in this study: Participant History 1. Participant has a history of persistent chronic or active infection(s) requiring hospitalization or treatment with parenteral anti-infectives within 30 days, or oral anti-infectives within 14 days prior to the first dose of study drug administration. 2. Participant has a history or evidence of active TB. 3. Participant has a history of malignancy within 5 years prior to Screening, except completely treated in situ carcinoma of the cervix and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin. 4. Participant has a history of clinically significant medical conditions or any other reason (eg, clinically significant drug or alcohol abuse) that the investigator determines would interfere with the participant's participation in this study or would make the participant an unsuitable candidate to receive study drug. 5. Participant has known hypersensitivity to IRL201805 or its excipients (ie, penicillin). 6. Participant is currently enrolled in another clinical study and/or has previously been enrolled in the current study. Diagnosis and Disease Activity: 7. Participant has a history of being exposed to > 1 biologic (bDMARD) or targeted synthetic (tsDMARD) therapy for RA. Participants with exposure to 1 bDMARD and 1 tsDMARD are not eligible. Concomitant Medications: 8. Participant is taking systemic glucocorticoids (GCs) > 7.5 mg/day prednisone equivalent. Stable dose of GC (= 7.5 mg/day prednisone equivalent) started at least 4 weeks prior to the Baseline/Day 1 visit is permitted. 9. Participant has been treated with an investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug. 10. Participant has been treated with intra-articular, intramuscular, IV, trigger point or tender point, intrabursa, or intratendon sheet corticosteroids in the preceding 4 weeks prior to the first dose of the study drug. 11. Participant has received a live vaccine within 4 weeks prior to the first dose of study drug or expects to need a live vaccination during study participation. Contraception: 12. Participant is a female who has a positive pregnancy test at Screening or Baseline/Day 1. 13. Participant is a female who is breastfeeding or considering becoming pregnant during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess increasing doses of IRL201805 on the treatment of rheumatoid arthritis (RA) as measured by change from baseline in the disease activity score at Week 12 compared with placebo treatment in patients.;Secondary Objective: To evaluate the efficacy of IRL201805 compared to placebo based on the Clinical Disease Activity Index (CDAI) To evaluate the efficacy of IRL201805 compared to placebo on other markers of RA disease activity over time To evaluate the effects of IRL201805 compared to placebo on blood markers of RA To evaluate the generation of potential anti-drug antibodies (ADAs) To evaluate the efficacy of IRL201805 compared to placebo on protocol-defined patient reported outcome (PRO) and clinician reported outcome (CRO) questionnaires;Primary end point(s): Primary Endpoint: •Change from baseline in DAS28-CRP at Week 12 ;Timepoint(s) of evaluation of this end point: Screening, Baseline/Day1, Week 4, Week 8, Week 12, Week 12, Week 18, Week 24/EoT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: • Change from baseline in CDAI and SDAI over time through Week 24 • Proportion of participants achieving implied clinical remission (CR) at Week 12. CR is defined as DAS28-CRP < 2.6 • Proportion of participants achieving implied low disease activity (LDA) at Week 12. LDA is defined as DAS28-CRP = 3.2 • Proportion of participants achieving LDA or CR based on CDAI criteria over time through Week 24 • ACR20/50/70 response rates determined based on 20%/50%/70% or greater improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and = 3 of the 5 measures of Patient's Assessment of Pain (Visual Analog Scale [VAS]), Patient's Global Assessment of Disease Activity (PtGA), Physician’s Global Assessment of Disease Activity (PhGA), Health Assessment Questionnaire Disability Index (HAQDI), and acute phase reactant (hsCRP or erythrocyte sedimentation rate [ESR]) as assessed over time through Week 24 • Change from baseline in individual components of ACR response over time through Week 24 • Change from baseline in DAS28-CRP and DAS28–ESR over time through Week 24 • Measurement of the following serologic markers: circulating levels of immunoglobulin (IG), titre anti-citrullinated protein/peptide antibody (ACPA), hsCRP, and ESR, rheumatoid factor over time through Week 24 • Measurement of plasma concentrations of IRL201805 • Measurement of any ADA response • Change from baseline for the following outcome (ie, PRO or CRO) instruments: Health Assessment Questionnaire – Disability Index (HAQDI); pain VAS; 36Item ShortForm Survey (SF-36). The use of Global Assessments: Patient Global Assessment, Physician Global Assessment, and fatigue (Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F]) over time through Week 24 ;Timepoint(s) of evaluation of this end point: Please refer to protocol. | — |
Countries
Bulgaria, Czechia, Czech Republic, Georgia, Germany, Hungary, Latvia, Poland, Spain, United Kingdom
Contacts
Public ContactBeth Alley
Revolo Biotherapeutics Ltd
Outcome results
None listed