Aminopterin Dose Finding Treatment for Methotrexate-Naïve Rheumatoid Arthritis

NCT01724931 | Completed Phase 2

• 1 other identifier: Syntrix-AMT-RA-202
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to determine whether aminopterin is effective in the treatment of rheumatoid arthritis (RA).

Conditions

Rheumatoid Arthritis

Keywords

antifolate; antiinflammatory; autoimmune disease; hematological treatment; rheumatic disease; folic acid antagonist; enzyme inhibitor

Outcome Measures

Primary Outcomes (1)

• ACR20

  The primary efficacy endpoint, determined at study day 84 or last observation carried forward (LOCF), is the percent of subjects who obtain ACR20 in the 3 mg/week LD-AMT dose compared to placebo.

  Study Day 84

Secondary Outcomes (1)

• ACR20

  Study Day 84

Other Outcomes (1)

• Adverse Event

  Study Day 126

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo once weekly

Drug: placebo

3 mg LD-Aminopterin

EXPERIMENTAL

3 mg LD-aminopterin once weekly

Drug: LD-aminopterin

1 mg LD-aminopterin

EXPERIMENTAL

1 mg LD-aminopterin once weekly

Drug: LD-aminopterin

Interventions

LD-aminopterin DRUG

1 mg LD-aminopterin; 3 mg LD-Aminopterin

placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 years of age.
• A diagnosis of RA established by the ACR/EULAR 2010 criteria applied to patients who: 1) have \>1 joint with definite clinical synovitis (swelling); 2) with the synovitis not better explained by another disease.
• Add scores of categories A-D; a score \>6/10 is required for study entry.
• A. Joint involvement:
• large joint=0; 2-10 large joints=1; 1-3 small joints (with or without involvement of large joints=2; 4-10 small joints (with or without involvement of large joints)=3; \>10 joints (at least 1 small joint)=5.
• B. Serology (at least 1 test result is needed for classification):
• Negative RF and negative ACPA=0; Low-positive RF or low-positive ACPA=2; High-positive RF or high-positive ACPA=3.
• C. Acute-phase reactants (at least 1 test result is needed for classification):
• Normal CRP and normal ESR=0; Abnormal CRP or abnormal ESR=1.
• D. Duration of symptoms:
• less than 6 weeks=0; 6 weeks or greater=1.
• \. Class I, II or III functional according to the ACR 1992 revised criteria for the classification of global functional status in RA.
• \. RA is active, defined as ≥ 6 swollen joints and ≥ 6 tender joints.
• \. Ability to understand and sign written informed consent.
• \. For sexually active men and for women of childbearing potential, an adequate form of contraception.

You may not qualify if:

• Known history of hepatitis, HIV infection, interstitial lung disease.
• Alcohol consumption on a regular basis and unwilling, or unable, to discontinue this consumption during the study period.
• Prior methotrexate or aminopterin therapy.
• Prior biologic drug therapy (e.g., etanercept, adalimumab, infliximab).
• Within 2 weeks prior to Study Day 0, or on Study Day 0, or at any time during the study, use of any of the following medications that may result in drug/drug interactions with AMT: trimethoprim with or without sulfamethoxazole; sulfonamides; sulfonylureas; pyrimethamine; triamethamine; dipyridamole; colchicine; probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e., leucovorin).
• At Study Day 0 use of DMARDs and biologics (except antimalarials) including oral or injectable gold, azathioprine, penicillamine, sulfasalazine or cyclosporine. Subjects previously treated with any of these medications are eligible provided a 28 day wash-out is completed prior to Study Day 0. Antimalarial can be continued at the same dose if they have been administered at the same dose for 8 weeks before Study Day 0, and they will be administered at the same dose throughout the study. NSAIDs or corticosteroid (≤ 10 mg prednisone or equivalent/day) may be continued at the same dose if they have been used at a stable dose for two weeks prior to Study Day 0, and will be continued at the same doses throughout the study.
• Use of corticosteroids in excess of 10 mg prednisone or equivalent/day.
• Known concurrent malignancy except basal or squamous cell skin carcinoma, or cervical carcinoma in situ.
• Concurrent participation in another clinical trial involving experimental treatment within 30 days of Study Day 0.
• Current and uncontrolled infection, cardiovascular, renal, pulmonary, hepatic or GI conditions that will interfere with the conduct of the trial or pose a morbid risk.
• Investigator's opinion that a concurrent disease or condition impairs the subject's ability to complete the trial: includes psychological, familial, sociological, geographical or medical conditions.

Sponsors & Collaborators

• Syntrix Biosystems, Inc.: lead

Study Sites (15)

Centre of Immunobiologic Therapy, State Institution "Institute of Emergency and Reconstructive Surgery

Donets'k, 83045, Ukraine

Location

Department of Hospital Therapy #1, Regional Clinical Hospital for occupational diseases 104

Donetsk, 83059, Ukraine

Location

Communal Establishment of Health Protection, Regional Hospital of Veterans of War, Rheumatology Department

Kharkiv, 61137, Ukraine

Location

Department of Rheumatology, Communal Establishment of Health Protection "Kharkiv City Clinical Hospital #8"

Kharkiv, 61178, Ukraine

Location

National Scientific Center "M.D. STRAZHESKO INSTITUTE OF CARDIOLOGY, MAS OF UKRAINE"

Kyiv, 03151, Ukraine

Location

Department of Rheumatology and Allergology, Kyiv Regional Clinical Hospital №1

Kyiv, 04107, Ukraine

Location

Lviv Regional Clinical Hospital, Department of Rheumatology

Lviv, 79010, Ukraine

Location

Department of Cardio-Rheumatology, Communal Institution "Odesa Regional Clinical Hospital"

Odesa, 65025, Ukraine

Location

Crimean State Medical University n.a. S.I. Georgievsky based on Rheumatology Department of Crimean Republic Institution "Clinical Territorial Medical Association "University Clinic"

Simferopol, 95017, Ukraine

Location

Railway Clinical Hospital of Uzhorod Station of Lviv Railroad Administration, Therapeutic Department

Uzhhorod, 88009, Ukraine

Location

Department of Rheumatology, Vinnytsya Regional Clinical Hospital n.a. M.I

Vinnytsa, 21018, Ukraine

Location

Zaporizhzhya City Multiple Discipline Clinical Hospital #9, Department of Therapy

Zaporizhzhya, 69065, Ukraine

Location

Department of Rheumatology, Zaporizhzhia Regional Clinical Hospital

Zaporizhzhya, 69600, Ukraine

Location

Department of Therapy, City Clinical Hospital № 6

Zaporizhzhya, Ukraine

Location

Department of Therapy, City Hospital № 7

Zaporizhzhya, Ukraine

Location

Related Publications (1)

• Menter A, Thrash B, Cherian C, Matherly LH, Wang L, Gangjee A, Morgan JR, Maeda DY, Schuler AD, Kahn SJ, Zebala JA. Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter. J Pharmacol Exp Ther. 2012 Sep;342(3):696-708. doi: 10.1124/jpet.112.195479. Epub 2012 May 31.

  PMID: 22653877 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid; Autoimmune Diseases; Rheumatic Diseases

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Study Officials

• Stuart Kahn, MD, MS

  Syntrix Biosystems, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2012
• First Posted: November 12, 2012
• Study Start: February 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: February 1, 2015
• Last Updated: May 20, 2015

Record last verified: 2015-05

Locations

UA (15)