A Study of Two Doses of MRC375 in Moderate to Severe Rheumatoid Arthritis Patients

This study is currently recruiting participants.
Verified November 2012 by Molecular Research Center, Inc.
Sponsor:
Collaborators:
Camargo Pharmaceutical Services
Clin Data Services
Harrison Clinical Research
BARC Global Central Laboratory
Bilcare Global Clinical Supplies
Information provided by (Responsible Party):
Molecular Research Center, Inc.
ClinicalTrials.gov Identifier:
NCT01408602
First received: August 2, 2011
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

This study will treat moderate to severe rheumatoid arthritis with MRC375 (either 75 mg 3 times a day, 150 mg 3 times a day or placebo 3 times a day)in patients 18 years of age or older that can be currently on low doses of methotrexate or can stop treatment of current RA medications to enter the study. Safety of MRC375 will also be evaluated. There are up to 8 clinic visits over 24 weeks.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: MRC375
Drug: Matching Placebo
Drug: MRC375 150mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 24-week, Phase 2, Double-blind, Placebo-controlled, Randomized Study to Assess the Safety and Efficacy of 2 Doses of MRC375 in Patients With Moderate to Severe Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Molecular Research Center, Inc.:

Primary Outcome Measures:
  • Efficacy evaluated of both doses of MRC375 compared to placebo after 24 weeks of treatment as measured by the rate of achievement of 20% improvement in ACR criteria [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    evaluate efficacy of both doses of MRC375 compared to placebo after 24 weeks of treatment, as measured by a rate of achievement of 20% improvement in American College of Rheumatology (ACR) criteria (ACR20) at Week 24


Secondary Outcome Measures:
  • Safety and tolerability of both doses of MRC375 [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    evaluate the safety and tolerability of both doses of MRC375 tablets

  • Compare the Efficacy of two doses of MRC375 when compared to a placebo for the change from baseline screening in each of the individual ACR components measuring RA after 24 weeks of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    compare the efficacy of 2 doses of MRC375 tablets (75 mg tid and 150 mg tid) when compared to placebo for the change from baseline screening in each of the individual ACR components measuring rheumatoid arthritis (RA) after 24 weeks of treatment.


Estimated Enrollment: 300
Study Start Date: November 2011
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MRC375 75 mg
MRC375 (enteric coated Tetracycline) 75 mg 3 times a day
Drug: MRC375
MRC 375 (enteric coated Tetracycline) 75mg 3 times a day for 24 weeks.
Experimental: MRC375 150mg
MRC375 (enteric coated Tetracycline) 150mg 3 times a day for 24 weeks.
Drug: MRC375 150mg
MRC375 (enteric coated Tetracycline) 150mg 3 times a day for 24 weeks
Placebo Comparator: Placebo
Placebo
Drug: Matching Placebo
Matching Placebo 3 times a day for 24 weeks. Early escape at week 16,20.

Detailed Description:

This is a double-blind, randomized, placebo-controlled study to assess the safety and efficacy of MRC375 at 75 mg or 150 mg with matching placebo (taken tid with meal or light snack) in patients with moderate to severe RA. Patients will be randomized to one of the following study arms for 24 weeks:

  • Treatment 1, Placebo: 2 tablets taken tid
  • Treatment 2, MRC375: 1 tablet of 75 mg tetracycline HCL plus 1 matching placebo tablet taken tid. Total daily dose = 225 mg.
  • Treatment 3, MRC375: 2 tablets of 75 mg tetracycline HCL taken tid. Total daily dose = 450 mg.

Study medication should be taken within 30 minutes of a meal or light snack (either before or after).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is 18 years of age
  2. Is diagnosed with moderate to severe adult onset RA > = 6 months duration, as defined by the 1987 ACR classification criteria
  3. Has moderate to severe RA as defined by:

    • ≥4 tender joints/painful (28 joint count) at screening
    • ≥4 swollen joints (28 joint count) at screening
  4. Has a Health Assessment Questionnaire (HAQ) of >0
  5. Has a physician global assessment (Likert scale) of >0
  6. Has a patient global assessment of pain (Likert scale) of >0
  7. Has a patient assessment of pain (Likert scale) of >0
  8. Has stable doses of the following allowable medications during the study, if applicable:

    • Stable dose of NSAIDs or other analgesics for at least 2 weeks prior to administration of study drug at regulatory approved doses
    • Stable dose of methotrexate 7.5 mg to 25 mg/day once weekly for at least 6 weeks prior to administration of study drug (no changes in dosing regimen for 4 weeks prior to screening)
    • Stable dose of hydroxychloroquine either monotherapy or in combination with methotrexate 8 weeks prior to administration of study drug
  9. Is a non-pregnant, non-lactating female who is postmenopausal, naturally or surgically sterile, or who agree to use effective contraceptive methods throughout the course of the study. Postmenopausal is defined as at least 12 months natural spontaneous amenorrhea
  10. If female of childbearing potential, must agree to use one of the following acceptable birth control methods:

    • Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to screening, hysterectomy, or bilateral oophorectomy);
    • Intrauterine device (IUD) in place for at least 3 months prior to first dose of study drug;
    • Abstinence (not having sexual intercourse);
    • Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening and through study completion;
    • Stable hormonal contraceptive for at least 3 months prior to study and through study completion
  11. If female of childbearing potential, has a negative serum hCG pregnancy test at screening
  12. Is able to swallow whole tablets of orally administered medication
  13. Is able to understand and provide signed informed consent.

Exclusion Criteria:

  1. Has been diagnosed with any other inflammatory arthritis (eg, psoriatic arthritis)
  2. Has a secondary type of arthritis (eg, osteoarthritis) that would interfere with study evaluations
  3. Has taken the following drugs within the timeframe specified below:

    • Infliximab, etanercept, adalimumab, abatacept, or other biological therapies (except rituximab) - Within 12 weeks prior to the administration of study drug;
    • Rituximab - Within 12 months prior to the administration of study drug;
    • Disease-modifying antirheumatic drugs (DMARDs) or other anti-rheumatic therapies not specified above including but not limited to: sulfasalazine, gold, leflunomide, penicillamine, dapsone, azathioprine, 6-mercaptopurine, chlorambucil, cyclophosphamide, cyclosporin, mycophenolate mofetil - Within 12 weeks prior to the administration of study drug;
    • Any steroids (glucocorticoids); glucocorticoids must be discontinued for at least 4 weeks prior to administration of study drug. Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to administration of study drug.
    • Note: Use of probiotics is allowed and is NOT an exclusion criterion.
  4. Has a uncontrolled symptoms of fibromyalgia with sufficient symptoms requiring treatment (NOTE: patients on a stable dose of treatment for symptoms of fibromyalgia ≥ 4 weeks will be allowed in the study.)
  5. Has a history of allergic reaction to tetracycline or other related drugs
  6. Had major surgery or trauma within 28 days prior to screening
  7. Is concurrently using minocycline or doxycycline (washout of 4 weeks required before the administration of study drug)
  8. Patients who are on chronic antibiotics or who are on antibiotics for GI infections (such as Clostridium difficile)
  9. Has clinically significant ECG abnormalities
  10. Has any clinically significant abnormal laboratory test results found during medical screening including: AST or ALT > 2 x upper limit of normal or serum creatinine > 2.0 mg/dL
  11. Has clinically significant history or presence of any gastrointestinal pathology (eg, chronic diarrhea, inflammatory bowel disease, acute diverticulitis), irritable bowel syndrome, unresolved gastrointestinal symptoms (eg. diarrhea, vomiting, symptoms of acute diverticulitis), liver or kidney disease, gastric bypass, gastric stapling, use of Lap-Band®, or other conditions known to or which might interfere with the absorption, distribution, metabolism, or excretion of the drug
  12. Has any historical or active neurological, endocrine, cardiovascular, pulmonary, hematological, psychiatric, or metabolic disease that is considered clinically significant by the Investigator
  13. Has known history of HIV, hepatitis B or C (patients that have positive hepatitis B serology due to prior vaccination will be allowed in the study)
  14. Has an active malignancy of any type or history of malignancy. Patients who have a history of a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma (ie. non melanoma skin cancer)and/or localized carcinoma in situ of the cervix are eligible. Patients with a history of other malignancies that have been treated and who have no evidence of recurrence for at least 5 years before study enrollment are also eligible.
  15. Has difficulty swallowing tablets
  16. Is ACR Functional Class IV (limited ability to perform usual self-care, vocational, and avocational activities)
  17. Has known or suspected pregnancy, planned pregnancy, or lactation (for female patients)
  18. Has clinically significant mental illness (to be determined by the Investigator)
  19. Has a history in the last 2 years or current evidence of abuse of illicit drugs, prescription medications, or alcohol that, in the opinion of the Investigator, would interfere with adherence to study requirements. Has exposure to any investigational agent within 30 days prior to study entry.
  20. Was previously enrolled in this study
  21. Has recent history of bacterial intestinal tract infection (gastroenteritis, colitis, diverticulitis, appendicitis)
  22. Has a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the patient at undue risk
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01408602

Contacts
Contact: Cynthia Phurrough 513-618-0337 cphurrough@camargopharma.com

Locations
United States, Alabama
Mobile Diagnostic Center Rheumatology Terminated
Mobile, Alabama, United States, 36608
United States, California
Valerius Medical Group Recruiting
Long Beach, California, United States, 90806
Contact: Michelle Pratt       michelle@valeriusmedical.com   
Principal Investigator: Nathaniel Neal, MD         
Trial Concierge/Pacific Clinical Studies Recruiting
Los Alamitos, California, United States, 90720
Principal Investigator: Etsegenet Ayele, MD         
Axis Clinical Trials Terminated
Los Angeles, California, United States, 90036
United States, Florida
Riverside Clinical Research Recruiting
Edgewater, Florida, United States, 32132
Principal Investigator: Susan Hole, DO         
Global Clinical Professionals Recruiting
Miami, Florida, United States, 33156
Principal Investigator: Edgar Marin, MD         
The Arthritis Center Recruiting
Palm Harbor, Florida, United States, 34684
Principal Investigator: Mitchell Lowenstein, MD         
Lakeview Medical Research Recruiting
Summerfield, Florida, United States, 34491
Principal Investigator: Khai Chang, MD         
United States, Kansas
Analan Clinical Research Recruiting
Lenexa, Kansas, United States, 66219
Contact: Rebecca Schulz    913-221-0421    rschulz@analabcr.com   
Principal Investigator: Stephen Maddock, MD, PhD         
United States, Kentucky
Trial Concierge Terminated
Owensboro, Kentucky, United States, 42303
United States, Nebraska
Quality Clinical Research, Inc. Terminated
Omaha, Nebraska, United States, 68114
United States, Nevada
Advanced BioMedical Research of America Recruiting
Las Vegas, Nevada, United States, 89123
Principal Investigator: Vrijendra H Kumar, MD         
Arthritis Center of Reno Recruiting
Reno, Nevada, United States, 89502
Contact: Serafin Herrera    775-786-9100    renojoints@comcast.net   
Principal Investigator: Henry Malin Prupas, MD         
United States, North Carolina
PMG Research of Salisbury Recruiting
Salisbury, North Carolina, United States, 28144
Principal Investigator: Rakesh C Patel, MD         
United States, Ohio
Providence Health Partners Recruiting
Dayton, Ohio, United States, 45439
Principal Investigator: Edward Hubach, MD         
Paramount Medical Research & Consulting, LLC Recruiting
Middleburg Heights, Ohio, United States, 44130
Principal Investigator: Isam Diab, MD         
United States, Virginia
The Center for Excellence in Aging and Geriatric Health Recruiting
Williamsburg, Virginia, United States, 23185
Principal Investigator: Paul E Evans, III, MD         
United States, Washington
Apex Clinical Research Terminated
Kennewick, Washington, United States, 99336
South Puget Sound Clinical Research Center Recruiting
Olympia, Washington, United States, 98502
Principal Investigator: Mark Layton, MD         
Sponsors and Collaborators
Molecular Research Center, Inc.
Camargo Pharmaceutical Services
Clin Data Services
Harrison Clinical Research
BARC Global Central Laboratory
Bilcare Global Clinical Supplies
  More Information

No publications provided

Responsible Party: Molecular Research Center, Inc.
ClinicalTrials.gov Identifier: NCT01408602     History of Changes
Other Study ID Numbers: MRC2011-001
Study First Received: August 2, 2011
Last Updated: November 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Molecular Research Center, Inc.:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tetracycline
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014