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Rheumatoid ArthritisPhase 2NCT01724931

Aminopterin Dose Finding Treatment for Methotrexate-Naïve Rheumatoid Arthritis

A Phase 2 study testing LD-aminopterin in people with Rheumatoid Arthritis, run by Syntrix Biosystems, Inc. at 15 sites in Ukraine.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
LD-aminopterin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
175 participants
Where
15 sitesUkraine
Study dates
Feb 2013to Feb 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • > 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.
  • Joint involvement:
  • 1 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.
  • Serology (at least 1 test result is needed for classification):
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  • Negative RF and negative ACPA=0; Low-positive RF or low-positive ACPA=2; High-positive RF or high-positive ACPA=3.
  • Acute-phase reactants (at least 1 test result is needed for classification):
  • Normal CRP and normal ESR=0; Abnormal CRP or abnormal ESR=1.
  • Duration of symptoms:
  • less than 6 weeks=0; 6 weeks or greater=1.
  • 3. Class I, II or III functional according to the ACR 1992 revised criteria for the classification of global functional status in RA.
  • 4. RA is active, defined as ≥ 6 swollen joints and ≥ 6 tender joints.
  • 5. Ability to understand and sign written informed consent.
  • 6. For sexually active men and for women of childbearing potential, an adequate form of contraception.
  • 7. For pre-menopausal women, a negative pregnancy test, obtained within 1 week prior to first study drug dose.
  • 8. Negative serology for hepatitis B and hepatitis C.
  • 9. The following screening laboratory blood tests must have the following values, or not clinically significant as determined by the PI and Medical Monitor: WBC WNL; absolute neutrophil count > lower limit of normal; platelet count WNL; hemoglobin >10.0 g/dL; AST WNL.
  • 10. Adequate renal function: GFR estimated by Cockcroft-Gault formula >60 ml/min

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Ukraine15 sites

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

    Donets'k, 83045

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

    Donetsk, 83059

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

    Kharkiv, 61137

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

    Kharkiv, 61178

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

    Kyiv, 03151

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

    Kyiv, 04107

  • Lviv Regional Clinical Hospital, Department of Rheumatology

    Lviv, 79010

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

    Odesa, 65025

  • 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

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

    Uzhhorod, 88009

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

    Vinnytsa, 21018

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

    Zaporizhzhya, 69065

  • Department of Rheumatology, Zaporizhzhia Regional Clinical Hospital

    Zaporizhzhya, 69600

  • Department of Therapy, City Clinical Hospital № 6

    Zaporizhzhya

  • Department of Therapy, City Hospital № 7

    Zaporizhzhya

Other trials in Ukraine

About this study

Official title: A Phase 2 Double-Blind, Placebo-Controlled, Randomized Dose Finding Study For The Efficacy And Safety Of Aminopterin In Methotrexate-Naive Rheumatoid Arthritis

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

Read the detailed description

This is a double-blind, randomized, placebo-controlled, dose ranging study that will evaluate the safety, efficacy, and pharmacokinetic properties (the absorption, distribution and excretion) of aminopterin following oral administration by subjects with active rheumatoid arthritis (≥ 6 tender and ≥ 6 swollen joints) who have not been treated with methotrexate (MTX). Subjects are randomized to one of three treatments: placebo, 1 mg of LD-aminopterin, or 3 mg of LD-aminopterin in a 1:1:1 ratio. The study hypothesis is that the 3 mg LD-aminopterin per week is effective at treating rheumatoid arthritis compared to placebo.

Being tested
LD-aminopterin, placebo
Keywords
antifolate, antiinflammatory, autoimmune disease, hematological treatment, rheumatic disease, folic acid antagonist, enzyme inhibitor
Medical subject headings
Arthritis, Rheumatoid, Autoimmune Diseases, Rheumatic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LD-aminopterinDrug

  • placeboDrug

Study groups in NCT01724931
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo once weekly
Receives: Drug: placebo
3 mg LD-AminopterinExperimental3 mg LD-aminopterin once weekly
Receives: Drug: LD-aminopterin
1 mg LD-aminopterinExperimental1 mg LD-aminopterin once weekly
Receives: Drug: LD-aminopterin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Study Day 84

Secondary outcomes (1)

  1. ACR20

    A secondary efficacy endpoint, determined at study day 84 or LOCF, is the percent of subjects who obtain ACR20 in the 1 mg LD-AMT/week dose.

    Measured: Study Day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2012 (estimated)
  2. Study startFeb 2013
  3. Primary completionSep 2014
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01724931
Sponsor's protocol ID
Syntrix-AMT-RA-202
Status last verified
May 2015
First submitted
7 Nov 2012
Last updated
20 May 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 22653877

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LD-aminopterin in people with Rheumatoid Arthritis, run by Syntrix Biosystems, Inc. at 15 sites in Ukraine.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ACR20 (time frame: Study Day 84). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01724931, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2015.

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