Phase 2b Study of MBS2320 in Participants With Methotrexate-Refractory RA

Study Overview
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Brief Summary
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Rheumatoid arthritis (RA) affects 1 percent of the population worldwide and up to 40 percent of patients don't respond to current treatments. MBS2320, the drug being tested in this trial, represents a new approach to treating RA, with the potential not only to reduce levels of inflammation but to also directly prevent bone damage. The aim of this project is to test the safety, tolerability and efficacy of MBS2320 in patients with RA in combination with an existing treatment, methotrexate. Approximately 224 participants with moderate to severe active RA who have not responded to treatment with Methotrexate will be enrolled from around 45 to 55 sites around the world. Participants will be randomly assigned to receive 1 of 3 doses of MBS2320 (5 mg, 20 mg, or 40 mg) or placebo (a dummy drug). The maximum duration of study participation for a participant will be 22 weeks, which consists of a Screening Period of up to 4 weeks, Treatment Period of 12 weeks, and a Follow-up Period of 6 weeks. Participants on the study will be asked to attend the hospital or clinic for regular visits during which they will have planned study assessments to evaluate the effectiveness, tolerability and safety of the study drug.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled, Dose-Ranging Phase 2b Study to Investigate the Efficacy & Safety of MBS2320 in Participants With Moderate to Severe Active Rheumatoid Arthritis With Inadequate Response to Methotrexate Alone

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: MBS2320 5 mg
* Drug: MBS2320 20 mg
* Drug: MBS2320 40 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with RA based on either the 1987-revised ACR classification criteria or the 2010 ACR/ EULAR criteria for ≥3 months prior to screening. Has active RA as defined by the following minimum disease activity criteria: ≥6 swollen joints (based on 66 joint counts) ≥6 tender joints (based on 68 joint counts) hsCRP > upper limit of normal reference range (ULN) Considered to be inadequately responding to oral or parenteral MTX therapy for ≥3 months and <10 years prior to screening and to be tolerating a dose of 15 to 25 mg per week. Participants should also be on a stable dose of folic acid (or equivalent). Except for MTX, must have discontinued all oral DMARDs prior to baseline visit. If participants are taking NSAIDs or acetaminophen for stable medical conditions, they should be receiving these medications at a stable dose for at least 4 weeks prior to baseline visit and the doses of the medications should be kept stable throughout the study. If participants are taking oral corticosteroids (equivalent to prednisolone ≤10 mg), or inhaled corticosteroids, they should be receiving these medications at a stable dose for at least 4 weeks prior to baseline visit for stable medical conditions. This list contains only key inclusion criteria. Exclusion Criteria: Abnormality in the 12-lead ECG, heart rate or blood pressure at screening. Any clinically significant neurological, GI, renal, hepatic, CV, psychiatric, respiratory, metabolic, endocrine, haematological, ophthalmic, or other major disorder which, in the opinion of the Investigator, would put the participant at risk by participating in the study. Any current malignancy or a history of malignancy within 5 years prior to screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Any other inflammatory or arthritic disease in addition to RA that may interfere with the study. Active infection that is clinically significant in the Investigator's opinion, or any infection requiring hospitalisation or treatment with intravenous antimicrobials ≤60 days of screening, or any infection requiring oral antimicrobial therapy ≤2 weeks of the baseline visit. Clinically significant features of arthroses that could interfer with study assessments and objectives. This list contains only key exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral capsule<br>|
| Experimental: MBS2320 5 mg<br> | Drug: MBS2320 5 mg<br>* Oral capsule<br>|
| Experimental: MBS2320 20 mg<br> | Drug: MBS2320 20 mg<br>* Oral capsule<br>|
| Experimental: MBS2320 40 mg<br> | Drug: MBS2320 40 mg<br>* Oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a successful composite clinical response according to the criteria for American College of Rheumatology 20% response (ACR20) | Achieving clinical response according to the criteria for ACR20: ≥20% improvement in 68-Tender Joint Count; ≥20% improvement in 66-SJC; and ≥20% improvement in at least 3 of the 5 following parameters: Physician's global assessment of disease activity Participant's global assessment of disease activity Participant's assessment of arthritis pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores | Difference in mean change from baseline in each RAMRIS score (synovitis, bone oedema, and bone erosion scores measured with MRI). | Week 12 | 
| Percentage of participants achieving clinical response according to the criteria for American College of Rheumatology 50% response (ACR50) | Achieving clinical response according to the criteria for ACR50: ≥50% improvement in 68-Tender Joint Count; ≥50% improvement in 66-SJC; and ≥50% improvement in at least 3 of the 5 following parameters: Physician's global assessment of disease activity Participant's global assessment of disease activity Participant's assessment of arthritis pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP) | Week 12 | 
| Percentage of participants achieving clinical response according to the criteria for American College of Rheumatology 70% response (ACR70) | Achieving clinical response according to the criteria for ACR70: ≥70% improvement in 68-Tender Joint Count; ≥70% improvement in 66-SJC; and ≥70% improvement in at least 3 of the 5 following parameters: Physician's global assessment of disease activity Participant's global assessment of disease activity Participant's assessment of arthritis pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP) | Week 12 | 
| Percentage of participants achieving DAS28-hsCRP remission | Difference in mean change from baseline in DAS28-hsCRP. DAS28-hsCRP is a composite score that includes 4 variables: tender and swollen joint counts (based on 28 joints each), participant's global assessment of disease activity, and hsCRP. | Week 12 | 
| Change in cartilage loss (CARLOS) scores | Change in cartilage loss in the hand and wrist from baseline measured with MRI and scored using a validated 9-point scale with 0.5 increments where 0.0 is no cartilage loss and 4.0 is complete ankylosis. | Week 12 | 
| Safety and tolerability of MBS2320 | Incidence of all grade adverse events | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis (RA), MBS2320