Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis (RA), MBS2320
Brief summary
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.
Interventions
DRUGMBS2320 5 mg
Oral capsule
DRUGMBS2320 20 mg
Oral capsule
DRUGMBS2320 40 mg
Oral capsule
DRUGPlacebo
Oral capsule
Sponsors
Modern Biosciences Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with RA based on either the 1987-revised ACR classification criteria or the 2010 ACR/ EULAR criteria for ≥3 months prior to screening. 2. 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) 3. 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). 4. Except for MTX, must have discontinued all oral DMARDs prior to baseline visit. 5. 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. 6. 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
1. Abnormality in the 12-lead ECG, heart rate or blood pressure at screening. 2. 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. 3. 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. 4. Any other inflammatory or arthritic disease in addition to RA that may interfere with the study. 5. 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. 6. Clinically significant features of arthroses that could interfer with study assessments and objectives. This list contains only key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Successful Composite Clinical Response According to the Criteria for American College of Rheumatology 20% Response (ACR20) | Week 12 | 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: 1. Physician's global assessment of disease activity 2. Participant's global assessment of disease activity 3. Participant's assessment of arthritis pain 4. Health Assessment Questionnaire - Disability Index (HAQ-DI) 5. High-sensitivity C-reactive protein (hsCRP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of MBS2320 | Week 12 | Incidence of all grade adverse events |
Countries
Bosnia and Herzegovina, Bulgaria, Chile, Czechia, Guatemala, Mexico, Poland, Serbia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MBS2320 5 mg MBS2320 5 mg once daily for 12 weeks | 62 |
| MBS2320 20 mg MBS2320 20 mg once daily for 12 weeks | 63 |
| MBS2320 40 mg MBS2320 40 mg once daily for 12 weeks | 61 |
| Placebo Matching placebo capsules were provided containing the same excipients as the MBS2320 capsules but minus the active drug. The dosing instructions were the same as for MBS2320. | 62 |
| Total | 248 |
Baseline characteristics
| Characteristic | MBS2320 5 mg | MBS2320 20 mg | MBS2320 40 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 9 Participants | 7 Participants | 10 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 54 Participants | 54 Participants | 52 Participants | 209 Participants |
| Age, Continuous | 54.0 Years STANDARD_DEVIATION 13.82 | 55.0 Years STANDARD_DEVIATION 12.48 | 53.0 Years STANDARD_DEVIATION 11.26 | 55.5 Years STANDARD_DEVIATION 11.42 | 55.0 Years STANDARD_DEVIATION 12.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 12 Participants | 11 Participants | 11 Participants | 5 Participants | 39 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 7 Participants | 11 Participants | 10 Participants | 39 Participants |
| Race (NIH/OMB) White | 39 Participants | 45 Participants | 39 Participants | 47 Participants | 170 Participants |
| Sex: Female, Male Female | 52 Participants | 59 Participants | 54 Participants | 48 Participants | 213 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 7 Participants | 14 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 62 | 0 / 63 | 0 / 61 |
| other Total, other adverse events | 4 / 62 | 16 / 62 | 8 / 63 | 13 / 61 |
| serious Total, serious adverse events | 0 / 62 | 0 / 62 | 0 / 63 | 2 / 61 |
Outcome results
Primary
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: 1. Physician's global assessment of disease activity 2. Participant's global assessment of disease activity 3. Participant's assessment of arthritis pain 4. Health Assessment Questionnaire - Disability Index (HAQ-DI) 5. High-sensitivity C-reactive protein (hsCRP)
Time frame: Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Successful Composite Clinical Response According to the Criteria for American College of Rheumatology 20% Response (ACR20) | 48.4 percentage of patients |
| MBS2320 5 mg | Percentage of Participants Achieving a Successful Composite Clinical Response According to the Criteria for American College of Rheumatology 20% Response (ACR20) | 49.2 percentage of patients |
| MBS2320 20 mg | Percentage of Participants Achieving a Successful Composite Clinical Response According to the Criteria for American College of Rheumatology 20% Response (ACR20) | 42.4 percentage of patients |
| MBS2320 40 mg | Percentage of Participants Achieving a Successful Composite Clinical Response According to the Criteria for American College of Rheumatology 20% Response (ACR20) | 57.7 percentage of patients |
Secondary
Safety and Tolerability of MBS2320
Incidence of all grade adverse events
Time frame: Week 12