A Study Investigating the Efficacy and Safety of ABT-494 given with Methotrexate in Subjects with Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2013-003984-72-LV
• Date of registration: 28/03/2014
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A Study Investigating the Efficacy and Safety of ABT-494 given with Methotrexate in Subjects with Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone.
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 with Background Methotrexate (MTX) in Subjects with Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone.
• Date of first enrolment: 30/05/2014
• Target sample size: 270
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003984-72
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Chile, Czech Republic, European Union, Hungary, Israel, Latvia, Mexico, Puerto Rico, Russian Federation, Serbia, Slovakia, South Africa, Spain, Turkey, Ukraine, United States

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult male or female, at least 18 years old.
2. Diagnosed with RA based on either the 1987-revised ACR classification criteria or the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria for = 3 months.
3. Have active RA as defined by the following minimum disease activity criteria:
• = 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
• = 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• hsCRP > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and anti-CCP at Screening.
4. Subjects must have been receiving oral or parenteral methotrexate therapy = 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study.
5. Except for MTX, subjects must have discontinued all oral DMARDs prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:
• = 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide
• = 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal)
6. Subject has a negative TB Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit.
7. Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone = 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen, tramadol, codeine, hydrocodone and propoxyphene taken PRN are allowed but may not be taken 24 hours prior to any study visit.
8. Subjects must have discontinued high potency opiates including (but not limited to): oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, morphine and meperidine at least 4 weeks prior to Baseline Visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 176
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 94

Exclusion criteria:
1. Female who is pregnant or breastfeeding.
2. Prior exposure to JAK inhibitor (e.g., tofacitinib, baricitinib).
3. Prior exposure to any investigational or approved biologic RA therapy.
4. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Baseline Visit.
5. Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7).
6. Subject has been treated with intra-articular, intramuscular, intravenous, intra-bursa, or intra-tendon sheath administration of corticosteroids in the preceding 8 weeks prior to the Baseline Visit.
7. Screening laboratory values meeting the following criteria:
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN
• Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m2
• Total white blood cell count (WBC) < 3,000/µL
• Absolute neutrophil count (ANC) < 1,200/µL
• Platelet count < 100,000/µL
• Absolute lymphocytes count < 750/ µL
• Hemoglobin < 9 gm/dL


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Rheumatoid Arthritis (RA)
MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: ABT 494 3mg
Pharmaceutical Form: Capsule
INN or Proposed INN: ABT 494
Current Sponsor code: ABT 494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: ABT 494 12mg
Pharmaceutical Form: Capsule
INN or Proposed INN: ABT 494
Current Sponsor code: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): ACR20 response rate.

Main Objective: The primary objective is to compare the safety and efficacy of multiple doses of ABT-494
versus placebo in subjects with moderately to severely active RA on stable background MTX therapy who have not shown an adequate response to MTX alone.

Timepoint(s) of evaluation of this end point: Week 12

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints of this study are ACR50/70 response rates at Week 12, the proportion of subjects achieving low disease activity (LDA) or clinical remission (CR) based on DAS28 [CRP] and CDAI criteria at Week 12, and the proportion of subjects achieving CR based on DAS28 [CRP] and CDAI criteria at Week 12.

Timepoint(s) of evaluation of this end point: Week 12

Secondary ID(s)

M13-537

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 15/07/2016
• Date Completed: 02/07/2015
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-003984-72/results