Arthritis, Rheumatoid
Conditions
Keywords
arthritis, rheumatoid, methotrexate, leflunomide
Brief summary
The purpose of this study is to determine the safety and tolerability of PRTX-100 when various doses are given 5 times at weekly intervals to patients with active rheumatoid arthritis that are taking methotrexate or leflunomide. The drug is administered in a physician's office via an intravenous infusion. PRTX-100 may be effective in rheumatoid arthritis by suppressing the immune responses. PRTX-100 is a highly-purified bacterial protein called Staphylococcal Protein A. In this study, cohorts of patients with active RA will receive sequentially higher doses of PRTX-100. There will be an inactive placebo cohort for comparison. Patients who do not attain low RA disease activity, by a commonly used measure, will leave the study at 3 months after their first dose of study drug.
Interventions
DRUGPRTX-100 at 1.5 mcg/kg
DRUGPRTX-100 at 3.0 mcg/kg
DRUGPRTX-100 at 6.0 mcg/kg
DRUGPRTX-100 at 12.0 mcg/kg
DRUGPRTX-100 at 240 mcg
DRUGPlacebo
Placebo administered via infusion once per week for 5 weeks
DRUGPRTX-100 at 420 mcg
Sponsors
Protalex, Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Active RA with disease duration of not less than 6 months * Concomitant stable methotrexate or leflunomide therapy
Exclusion criteria
* Diagnosis of any other inflammatory arthritis * ACR Functional Classification of IV * Significant systemic involvement secondary to RA (except for secondary Sjogren's syndrome) * History of clincally significant hypogammaglobulinemia, common variable immunodeficiency, or humeral immunodeficientncy * History of active tuberculosis, pro-thrombotic disorder, venous thrombosis requiring anti-coagulation, substance abuse, or serious psychiatric condition * History of allergy or hypersensitivity to aspirin or non-steroidal cyclooxygenase inhibitors, Staphylococcal protein A * History or presence of malignancy (except for surgically treated basal or squamous cell carcinoma of the skin at least 3 months prior to the start of study medication) * Uncontrolled diabetes or Type 1 diabetes * Unstable ischemic heart disease * Serious active or recurrent infection, hepatic cirrhosis, or other medically unstable condition * Systemic autoimmune diseases other than RA (such as systemic lupus erythematosus, scleroderma, inflammatory bowel disease, inflammatory myopathy) * Positive for HIV, hepatitis B surface antigen, or hepatitis C antibody * Pregnant or nursing females * Inadequate hepatic, renal, or hematologic function * Receipt of live vaccine within 5 weeks of start of study medication * Concomitant administration of other biologic or non-biologic DMARDS, corticosteroids, or anti-CD20 antibodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Screening up to 53 Weeks | Number, severity and attribution of relatedness of Adverse Events |
| Vital Signs and Physical Examinations | Screening up to 25 Weeks | Change from baseline in blood pressure, heart rate, body temperature, and physical examination parameters |
| ECG | Screening, first dose, 5th dose, 9 weeks, and 25 weeks | Change from baseline in heart rate, PR interval, QT/QTc interval and QRS duration |
| Clinical Laboratory Testing | Screening up to 25 weeks | Change from baseline in blood chemistry, hematology, and urinalysis values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | Prior to first dose, and at 4 weeks, 9 weeks, and 25 weeks | Proportion of patients sero-positive and/or with titers \> 512 at Week 4 and Week 9, the correlation between anti-product antibody and product clearance, and association between anti-product antibodies and adverse events. |
| Pharmacokinetics | Prior to first dose up to 72 hours after last dose of PRTX-100 | Plasma Cmax, AUC0-n, clearance and Vd. |
| Disease activity | Screening up to 53 weeks | Number and percentage of patients attaining an ACR20, ACR50 and ACR70 response at Week 13. Change from baseline in CDAI, RAPID 3, and DAS28-CRP scores. |
Countries
United States
Outcome results
None listed