A 12-week study of a new treatment, MBS2320, in Patients with Rheumatoid Arthritis Taking Methotrexate
- Conditions
- Rheumatoid ArthritisMedDRA version: 23.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2016-004038-24-RO
- Lead Sponsor
- Modern Biosciences plc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 108
1. Patients will be:
1.1. males or females (of childbearing or non-childbearing potential) with a diagnosis of RA by ACR/European League against Rheumatism (EULAR) 2010 criteria (or, for those patients diagnosed before 2010, ACR 1987 criteria) for =6 months.
1.2. between 18 and 75 years of age, inclusive.
2. Female patients of childbearing potential must not be pregnant, as documented by a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1, and must not be intending to become pregnant before the end of the study.
3. Patients must have active RA, defined as =6 swollen and/or =6 tender joints on 66/68 joint counts at screening and Day 1 (baseline).
4. Patients must have a high sensitivity CRP (hsCRP) result =1.5 × upper limit of normal (ULN) (0.3 mg/dL) or erythrocyte sedimentation rate (ESR) value =ULN (patients =50 years: 15 mm/hour [male], 20 or 25 mm/hour depending on site [female], >50 years: 20 mm/hour [male], 30 mm/hour [female]) at screening.
5. Patients must have been treated with, and tolerated, oral, SC or intramuscular (IM) MTX for a minimum of 90 days prior to screening, and must have been on a stable MTX dose between 7.5 and 25 mg once weekly for a minimum of 56 days prior to Day 1. Patients receiving MTX doses below 15 mg per week must have previously failed to tolerate a dose of 15 mg per week or higher.
6. Patients must have been treated with, and tolerated, folic acid, at a minimum dose of 5 mg per week, or be able and willing to commence such treatment from the screening visit.
7. Patients will have given their written informed consent to participate in the study and to abide by the study restrictions.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32
Medical conditions:
1. Patients who have an abnormality in heart rate or blood pressure at screening that in the opinion of the Investigator increases the risk of participating in the study.
2. Patients who have an abnormality in the 12-lead ECG at screening that in the opinion of the Investigator increases the risk of participating in the study.
2.1. Specific exclusion criteria are patients with QTc interval corrected for heart rate using Fridericia’s formula (QTcF) of >450 ms (males) or >460 ms (females) and patients with PR interval of >220 ms at screening (1 repeat allowed).
3. Patients who have a significant history of drug allergy, including to MBS2320 or excipients, as determined by the Investigator.
4. Patients who have, or who have a history of, any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, haematological or other major disorder (except for RA, or disorders associated with RA that, in the Investigator’s opinion, do not constitute a risk when taking the study medication and would not interfere with the study objectives) as determined by the Investigator.
5. Patients with 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.
6. Patients who have, or who have a history of, any other inflammatory or arthritic disease in addition to RA that may interfere with the study (such as polymyalgia rheumatica, giant cell arteritis, reactive arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis).
7. Patients who have known history of alcoholic hepatitis or non-alcoholic steatohepatitis.
8. Patients who have known history of opportunistic, chronic or recurrent infections.
Prior/concomitant therapy:
9. Patients who have received:
9.1. a live virus vaccination within the 90 days prior to Day 1 (1 year for bacille Calmette-Guerin [BCG] vaccination) or intend to receive a live virus vaccination during the study or within 28 days after study completion.
9.2. approved or investigational non-biological DMARDs (except MTX, sulfasalazine, chloroquine or hydroxychloroquine) such as tofacitinib, D-penicillamine, oral or parenteral gold salts, leflunomide, azathioprine, cyclosporine, tacrolimus and
mycophenolate mofetil within 30 days or 5 half-lives prior to Day 1, whichever is longer (1 year for leflunomide; unless there has been a washout procedure using cholestyramine or activated charcoal).
9.3. oral bisphosphonates within 6 months prior to Day 1 or once-yearly intravenous (IV) bisphosphonates within 1 year prior to Day 1.
9.4. any prior use of denosumab.
9.5. any prior use of the biological DMARD rituximab.
9.6. any biological DMARD therapy with agents such as abatacept, anakinra, tocilizumab, any therapeutic agent targeted at reducing TNFa such as adalimumab, golimumab, infliximab (or biosimilars thereof), or any approved or investigational monoclonal antibody or recombinant protein therapy or Prosorba column treatment within 60 days prior to Day 1.
9.7. two or more biological DMARD therapy agents where no therapeutic benefit was observed.
9.8. any prior use of cytotoxic agents (including, but not limited to, chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents).
9.9. non-steroidal anti-inflammatory drug (NS
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to determine the safety and tolerability of daily oral dosing of MBS2320 over 12 weeks in patients with active RA.;Secondary Objective: • To investigate whether there is evidence of a clinical benefit of MBS2320 over 12 weeks in patients with active RA, as assessed by the American College of Rheumatology 20% response (ACR20) and Disease Activity Score 28-C-reactive protein (DAS28-CRP).<br><br>• To evaluate the plasma concentrations of MBS2320 over 12 weeks in patients with active RA.;Primary end point(s): 1.Safety outcome measures include adverse events (AEs), vital signs, electrocardiograms (ECGs), clinical laboratory evaluations, physical examinations.<br><br>2. The main efficacy outcome measures are ACR20 and DAS28-CRP.;Timepoint(s) of evaluation of this end point: Throughout the 12 week study.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Exploratory efficacy outcome measures include patient and clinician reported outcomes, MRI of worst affected hand and wrist, DAS28-erythrocyte sedimentation rate, ACR 50% and 70% response (ACR50 and ACR70, respectively), percentage improvement in ACR components and number of patients achieving DAS28-CRP low disease activity.<br><br>2. Exploratory PD outcome measures are biomarkers (e.g. high sensitivity CRP, inflammatory cytokines and biomarkers of bone turnover) and peripheral blood leucocyte phenotype.<br><br>3. The PK outcome measures are MBS2320 and MBS2473 plasma concentrations.;Timepoint(s) of evaluation of this end point: Throughout the 12 week study.