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

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

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90036
      • Protalex Investigative Site
  • Florida
    • Sarasota, Florida, United States, 34239
      • Protalex Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Protalex Investigational Site
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Protalex Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Protalex Investigational Site
  • North Carolina
    • Salisbury, North Carolina, United States, 28144
      • Protalex Investigational Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Protalex Investigational Site
  • Texas
    • Allen, Texas, United States, 75013
      • Protalex Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.5 mcg/kg; PRTX-100 at 1.5 mcg/kg administered via infusion once per week for 5 weeks	Drug: PRTX-100 at 1.5 mcg/kg; Other Names: SpA; Staphylococcal Protein A
Experimental: 3.0 mcg/kg; PRTX-100 at 3.0 mcg/kg administered via infusion once per week for 5 weeks	Drug: PRTX-100 at 3.0 mcg/kg; Other Names: SpA; Staphylococcal Protein A
Experimental: 6.0 mcg/kg; PRTX-100 at 6.0 mcg/kg administered via infusion once per week for 5 weeks	Drug: PRTX-100 at 6.0 mcg/kg; Other Names: SpA; Staphylococcal Protein A
Experimental: 12.0 mcg/kg; PRTX-100 at 12.0 mcg/kg administered via infusion once per week for 5 weeks	Drug: PRTX-100 at 12.0 mcg/kg; Other Names: SpA; Staphylococcal Protein A
Experimental: 240 mcg; 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; Other Names: SpA; Staphylococcal Protein A
Placebo Comparator: Placebo; Placebo administered via infusion once per week for 5 weeks	Drug: Placebo; Placebo administered via infusion once per week for 5 weeks
Experimental: 420 mcg; 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; Other Names: SpA; Staphylococcal Protein A

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Protalex, Inc.
• Investigators: Study Director: William E Gannon, M.D., Protalex, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 12, 2012
• First Posted (Estimate): December 17, 2012

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: methotrexate; arthritis; leflunomide; rheumatoid
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: PRTX-100-104