GLPG0259 in Methotrexate-refractory Rheumatoid Arthritis

NCT01211249 | Completed Phase 2 DMC

• 2 other identifiers: GLPG0259-CL-2012009-015898-12
• Study Type: interventional
• Target: 30
• Locations: 5 countries
• Sites: 32

Brief Summary

Part A: 30 patients suffering from active rheumatoid arthritis despite continued treatment with methotrexate will receive once daily two capsules containing either GLPG0259 (25 mg/capsule) or matching placebo, for 12 weeks. In the course of the study the patients will be examined for severity of disease, as well as for any adverse effects that may occur. If needed, dosing may be split to one capsule twice daily, or reduced to one capsule of 25 mg. Part B: If results of Part A suggest test medication to have a therapeutic advantage over placebo and to be well-tolerated, more patients will be recruited for Part B, where various dosages will be assessed. These dosages will be established based on results from Part A.

Conditions

Rheumatoid Arthritis

Keywords

Methotrexate-refractory

Outcome Measures

Primary Outcomes (1)

• Efficacy

  The primary efficacy endpoint will be the number and percentage of subjects in each GLPG0259 dose group and placebo group achieving an American College of Rheumatology (ACR)20 (ACR20 response rate) at Week 12.

  12 weeks

Secondary Outcomes (3)

• Efficacy

  intermediate timepoints for 12 weeks

• Safety

  12 weeks

• Pharmacokinetics

  12 weeks

Study Arms (4)

GLPG0259 (Part A)

EXPERIMENTAL

Drug: GLPG0259 oral capsule

Placebo (Part A)

PLACEBO COMPARATOR

Drug: Placebo

GLPG0259 (Part B)

EXPERIMENTAL

Drug: GLPG0259 (Part B)

Placebo (Part B)

PLACEBO COMPARATOR

Drug: Placebo (Part B)

Interventions

GLPG0259 oral capsule DRUG

Two capsules, each containing 25 mg of GLPG0259 (i.e. 50 mg/day), to be given once daily; in case of adverse events the dose may be split over two administrations, or reduced to 25 mg/day (one single capsule)

GLPG0259 (Part A)

Placebo DRUG

Placebo capsules; two capsules to be taken in the morning, in case of adverse events the dose may be split over two administrations, or reduced to one single capsule

Placebo (Part A)

GLPG0259 (Part B) DRUG

Capsule, dosage to be established based on results of Part A

GLPG0259 (Part B)

Placebo (Part B) DRUG

Capsules, dosage to be established after Part A, and matching GLPG0259 (Part B)

Placebo (Part B)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have active RA (≥5 tender or painful joints on motion and ≥5 joints swollen AND a C-reactive protein (CRP) concentration ≥1.5 mg/dL).
• Must have been on methotrexate for ≥6 months at a stable dose of 7.5-25 mg/week for ≥12 weeks, to be continued throughout study;
• If on oral steroids, these should be at a dose ≤10 mg/day of prednisone eq and stable for ≥4 weeks prior to screening;
• If on NSAIDs, these must be at a stable dose for ≥2 weeks prior to screening;
• Women must have negative pregnancy test unless surgically sterile or post-menopausal for ≥1 year;
• Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for ≥12 weeks after the last dose of study drug.
• Informed consent

You may not qualify if:

• Must not have received treatment with DMARDs, other than background methotrexate;
• Must not be receiving or have received RA treatment with a biological agent, except if administered in a clinical study ≥six months prior to screening (12 months for rituximab or other B cell depleting agents);
• Must not have received any treatment with a cytotoxic agent, other than methotrexate, before screening (e.g. chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents);
• Must not have received intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
• Must not regularly be using aspirin or any other anti-coagulant medication;
• Must not have a known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator, such as anaphylaxis, requiring hospitalization;
• Must not have positive serology for human immunodeficiency virus (HIV)1 or 2 or hepatitis B or C, or any history of HIV or hepatitis from any cause with the exception of hepatitis A;
• Must not have a history of any inflammatory rheumatological disorders other than RA;
• Must not have undergone (or planned) surgical treatments for RA;
• Must not have symptoms of clinically significant illness other than RA (including but not limited to cardiopulmonary, renal, metabolic, hematologic, or psychiatric disorders) within three months prior to screening;
• Must not have a history of active infections requiring intravenous antibiotics within the past four weeks;
• Must not have a history of malignancy within the past five years (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence);
• Must not have a history of tuberculosis (TB) infection as determined by a positive diagnostic TB test result (defined as a positive QuantiFERON TB Gold test), AND a recent chest radiograph (both posterior-anterior and lateral views), read by a qualified radiologist, with evidence of current active TB or old inactive TB.
• Must not have been administered a live vaccine within four weeks prior to screening;
• Must not have participated in any investigational drug/device clinical study within four weeks prior to screening, in biological agents clinical studies within six months prior to screening, and B cell-depleting agent clinical studies within 12 months prior to screening;

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (32)

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

KU Leuven

Leuven, 3000, Belgium

Location

AZ Alma

Sijsele-Damme, 8340, Belgium

Location

UMC Leiden

Leiden, 2300RC, Netherlands

Location

Specjalistyczne Centrum Medyczne NZOZ NOWOMED

Krakow, 30-349, Poland

Location

"Linea Corporis" - Chirurgia Plastyczna Sp. z o.o.

Warsaw, 00-235, Poland

Location

Mokotowskie Centrum Osteoporozy S.C.

Warsaw, 02-620, Poland

Location

Synexus SCM Sp. z o.o.

Wroclaw, 50-088, Poland

Location

Akademia Medyczna im. Piastów Śląskich we Wroclawiu Katedra i Klinika Reumatologii i Chorób Wewnętrznych UM we Wrocławiu

Wroclaw, 50-556, Poland

Location

State Educational Institution of Higher Professional Education "Moscow State Medico-Stomatological University of Roszdrav" State Healthcare Institution of City Moscow "City Clinical Ordena Trudovogo Krasnogo Znameny Hospital #23 n.a. "Medsantrud"

Moscow, 109240, Russia

Location

State Healthcare Institution of city Moscow "City Clinical Ordena Trudovogo Krasnogo Znameny Hospital #23 n.a. "Medsantrud"

Moscow, 109240, Russia

Location

State Educational Institution of Higher Professional Education "Russian State Medical University of Roszdrav" State Healthcare Institution of City Moscow "City Clinical Hospital #15 n.a. O.M. Filatov"

Moscow, 111539, Russia

Location

State Healthcare Institution of City Moscow "City Clinical Hospital #4"

Moscow, 115093, Russia

Location

State Healthcare Institution of City Moscow "City Clinical Hospital #7"

Moscow, 115446, Russia

Location

Institution Russian Academy of Medical Sciences Scientific Research Institution of Rheumatology RAMN

Moscow, 115522, Russia

Location

State Healthcare Institution of City Moscow "City Clinical Hospital #1 n.a. Pirogov"

Moscow, 119049, Russia

Location

State Educational Institution of Higher Professional Education "Moscow State Medico-Stomatological University of Roszdrav" at the State Healthcare Institution of city Moscow "City Clinical Ordena Trudovogo Krasnogo Znameny hospital #23 n.a. "M

Moscow, 121374, Russia

Location

Saint-Petersburg State Healthcare Institution "City Hospital #26"

Moscow, 196247, Russia

Location

Saint-Petersburg State Healthcare Institution "City Pokrovskaya Hospital"

Saint Petersburg, 119106, Russia

Location

Saint-Petersburg State Healthcare Institution "City Mariinskiy Hospital"

Saint Petersburg, 191104, Russia

Location

Institution of Russian Academy of Sciences Saint-Petersburg Clinical Hospital RAN

Saint Petersburg, 194017, Russia

Location

State Educational Institution of Higher Professional Education "Saint-Petersburg State Pediatric Medical Academy of Roszdrav"

Saint Petersburg, 194100, Russia

Location

Chernivtsi Regional Clinical Hospital

Chernivtsi, 58000, Ukraine

Location

Donetsk City Hospital No5

Donetsk, 83000, Ukraine

Location

Kharkiv City Clinical Hospital No.27

Kharkiv, 61002, Ukraine

Location

Kharkiv City Clinical Hospital No.8

Kharkiv, 61176, Ukraine

Location

Kyiv City Clinical Hospital No.3

Kyiv, 02125, Ukraine

Location

Central Pool-type Clinical Hospital MoH of Ukraine

Kyiv, 04053, Ukraine

Location

Institute of Gerontology AMS of Ukraine

Kyiv, 04114, Ukraine

Location

University Clinic, Crimean Medical University

Simferopol, 95006, Ukraine

Location

Vinnytsia Regional Hospital

Vinnytsia, 21018, Ukraine

Location

Zaporizhzhia Regional Hospital

Zaporizhzhya, 69600, Ukraine

Location

Related Publications (1)

• Westhovens R, Keyser FD, Rekalov D, Nasonov EL, Beetens J, Van der Aa A, Wigerinck P, Namour F, Vanhoutte F, Durez P. Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial. Ann Rheum Dis. 2013 May;72(5):741-4. doi: 10.1136/annrheumdis-2012-202221. Epub 2012 Nov 17.

  PMID: 23161899 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

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

Study Officials

• Johan Beetens, PhD

  Galapagos NV

  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

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: September 29, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 26, 2011

Record last verified: 2011-04

Locations

NL (1); BE (3); UA (10); RU (13); PL (5)