Safety Study of PRTX-100 With Methotrexate or Leflunomide to Treat Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation, Safety and Tolerability Study of PRTX-100 in Combination With Methotrexate or Leflunomide in Patients With Active Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: PRTX-100 at 1.5 mcg/kg
* Drug: PRTX-100 at 3.0 mcg/kg
* Drug: PRTX-100 at 6.0 mcg/kg
* Drug: PRTX-100 at 12.0 mcg/kg
* Drug: PRTX-100 at 240 mcg
* Drug: Placebo
* Drug: PRTX-100 at 420 mcg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: 1.5 mcg/kg<br>PRTX-100 at 1.5 mcg/kg administered via infusion once per week for 5 weeks | Drug: PRTX-100 at 1.5 mcg/kg<br> <br> * Other names: SpA;|
| Experimental: 3.0 mcg/kg<br>PRTX-100 at 3.0 mcg/kg administered via infusion once per week for 5 weeks | Drug: PRTX-100 at 3.0 mcg/kg<br> <br> * Other names: SpA;|
| Experimental: 6.0 mcg/kg<br>PRTX-100 at 6.0 mcg/kg administered via infusion once per week for 5 weeks | Drug: PRTX-100 at 6.0 mcg/kg<br> <br> * Other names: SpA;|
| Experimental: 12.0 mcg/kg<br>PRTX-100 at 12.0 mcg/kg administered via infusion once per week for 5 weeks | Drug: PRTX-100 at 12.0 mcg/kg<br> <br> * Other names: SpA;|
| Experimental: 240 mcg<br>PRTX-100 at 240 mcg/dose administered via infusion once per week for 5 weeks then once every four weeks for 16 weeks thereafter. | Drug: PRTX-100 at 240 mcg<br> <br> * Other names: SpA;|
| Placebo Comparator: Placebo<br>Placebo administered via infusion once per week for 5 weeks | Drug: Placebo<br>* Placebo administered via infusion once per week for 5 weeks<br>|
| Experimental: 420 mcg<br>PRTX-100 at 420 mcg/dose administered via infusion once per week for 5 weeks then once every four weeks for 16 weeks thereafter. | Drug: PRTX-100 at 420 mcg<br> <br> * Other names: SpA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number, severity and attribution of relatedness of Adverse Events | Screening up to 53 Weeks | 
| Vital Signs and Physical Examinations | Change from baseline in blood pressure, heart rate, body temperature, and physical examination parameters | Screening up to 25 Weeks | 
| ECG | Change from baseline in heart rate, PR interval, QT/QTc interval and QRS duration | Screening, first dose, 5th dose, 9 weeks, and 25 weeks | 
| Clinical Laboratory Testing | Change from baseline in blood chemistry, hematology, and urinalysis values | Screening up to 25 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease activity | 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. | Screening up to 53 weeks | 
| Immunogenicity | 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. | Prior to first dose, and at 4 weeks, 9 weeks, and 25 weeks | 
| Pharmacokinetics | Plasma Cmax, AUC0-n, clearance and Vd. | Prior to first dose up to 72 hours after last dose of PRTX-100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arthritis, rheumatoid, methotrexate, leflunomide