Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis

NCT ID: NCT01999192

Last Updated: 2017-08-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 321 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-07-31

Brief Summary

The purpose of this study is to determine the efficacy and safety of three different Tregalizumab doses in combination with Methotrexate (MTX) in subjects who have active rheumatoid arthritis and an inadequate response to MTX alone.

The overall study duration is 24 weeks followed by a 24 week extension phase.

Detailed Description

The planned clinical study 986 (TREAT 2b) is a 24-week study in patients with Active rheumatoid arthritis (RA) who have had an inadequate response to Methotrexate (MTX) alone. The main phase of this study is followed by a 24-week extension phase for subjects meeting the respective entry criteria. Patients will be randomized to one of three different Active treatment groups or Placebo. The primary efficacy variable is the proportion of subjects with an ACR20 response after 12 weeks of double blinded treatment with the study medication based on observed cases in the FAS.

At Week 12, all subjects who had a minimum improvement of at least 20% (from baseline) in their tender joint count (TJC) and swollen joint count (SJC) continued on the same treatment. Subjects who had not demonstrated an improvement of at least 20% of TJC and SJC were assessed as non-responders. Non-responders who received placebo were randomized to an active treatment dose in a blinded manner. Non-responders who received active treatment were rolled up to the next highest dose in a blinded manner, apart from those already on the highest dose. These subjects remained on the highest dose.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dose Level 1 Tregalizumab

25mg Tregalizumab s.c. weekly

Group Type: EXPERIMENTAL

Tregalizumab

Intervention Type: DRUG

humanized anti-CD4 mAb

Dose Level 2 Tregalizumab

100mg Tregalizumab s.c. weekly

Group Type: EXPERIMENTAL

Tregalizumab

Intervention Type: DRUG

humanized anti-CD4 mAb

Dose Level 3 Tregalizumab

200mg Tregalizumab s.c. weekly

Group Type: EXPERIMENTAL

Tregalizumab

Intervention Type: DRUG

humanized anti-CD4 mAb

Placebo

Placebo s.c. weekly

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

identical end formulation buffer

Interventions

Tregalizumab

humanized anti-CD4 mAb

Intervention Type: DRUG

Placebo

identical end formulation buffer

Intervention Type: DRUG

Other Intervention Names

BT061

Eligibility Criteria

Inclusion Criteria

1. Subject demonstrates active RA according to the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA with functional class I-III for ≥6 months.

2. Subject receives oral or parenteral MTX treatment for ≥12 weeks (overall), with an unchanged mode of application and stable MTX dose of ≥15 mg per week (or ≥12.5 mg per week in case of MTX intolerance), but no more than the highest locally approved dose for RA, for ≥8 weeks prior to baseline. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons. If applicable, the dose of folic acid must be unchanged for ≥8 weeks prior to baseline.

3. Subject meets the following two criteria at both screening and baseline: - At least 6 swollen joints at 28-joint assessment. - At least 6 tender joints at 28-joint assessment.

4. Subject has an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) above the upper limit of normal (ULN) at screening. These tests may be repeated once during the screening period at the discretion of the investigator.

5. Subject is ≥18 and ≤75 years of age.

6. Subject has a body mass index ≥18 and ≤35 kg/m².

7. Subject receives treatment with corticosteroids ≤10 mg prednisone equivalent, stable for at least 4 weeks prior to baseline and during the study, if applicable.

8. Subject receives treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable for at least 2 weeks prior to baseline and during the study, if applicable.

9. Female subjects of childbearing potential: has both a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.

10. Subject is judged to be in good general health as determined by the investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (within 3 months before screening date is acceptable), and 12-lead electrocardiogram (ECG).

11. Subject has a cluster of differentiation 4 (CD4) cell count of > 400/µl at screening.

Exclusion Criteria

1. Subject has previous exposure to any systemic biologic therapy (e.g., etanercept, adalimumab, rituximab, abatacept, tocilizumab), to Janus kinase (JAK) or spleen tyrosine kinase (SYK) inhibitors, or to Tregalizumab. Previous treatment with an anti-TNF agent is allowed only, if all of the following criteria apply: - treatment was stopped for reasons other than lack of efficacy or adverse events (AEs) - treatment was stopped at least 12 weeks or five half-lives of the compound prior to baseline (whichever is longer), and - the treatment period did not exceed 6 weeks.

2. Subject received treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) apart from MTX in the 12 weeks prior to baseline, and for DMARD leflunomide in the 24 weeks prior to baseline (except where specific leflunomide wash-out procedures were completed, following applicable guidelines).

3. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to baseline. Inhaled corticosteroids for stable medical conditions are allowed.

4. Subject has undergone joint surgery in the 12 weeks prior to baseline (at joints to be assessed within the study) or has undergone major surgery (e.g., abdominal surgery) in the 8 weeks prior to baseline.

5. Subject has a history of acute inflammatory joint disease of an origin other than RA or subject has any other rheumatic disease other than RA (e.g., mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter's syndrome, fibromyalgia, systemic lupus erythematosus or any arthritis with onset prior to age 17 years). However, subjects may have secondary Sjögren's syndrome.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Biotest

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald van Vollenhoven, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Universitetssjukhuset, Solna

Locations

Study Site 07

Paradise Valley, Arizona, United States

Study Site 01

Springfield, Illinois, United States

Study Site 03

Lincoln, Nebraska, United States

Study Site 02

Clifton, New Jersey, United States

Study Site 04

North Charleston, South Carolina, United States

Study Site 05

Jackson, Tennessee, United States

Study Site 09

Houston, Texas, United States

Study Site 10

Katy, Texas, United States

Study Site 01

Plovdiv, , Bulgaria

Study Site 06

Plovdiv, , Bulgaria

Study Site 02

Sofia, , Bulgaria

Study Site 04

Sofia, , Bulgaria

Study Site 07

Sofia, , Bulgaria

Study Site 05

Stara Zagora, , Bulgaria

Study Site 03

Varna, , Bulgaria

Study Site 02

Rimouski, Quebec, Canada

Study Site 01

Saint-Jérôme, Quebec, Canada

Study Site 03

Bruntál, , Czechia

Study Site 05

Ostrava, , Czechia

Study Site 01

Prague, , Czechia

Study Site 04

Prague, , Czechia

Study Site 08

Prague, , Czechia

Study Site 09

Prague, , Czechia

Study Site 02

Uherské Hradiště, , Czechia

Study Site 07

Uherské Hradiště, , Czechia

Study Site 06

Zlín, , Czechia

Study Site 01

Tallinn, , Estonia

Study Site 03

Berlin, , Germany

Study Site 04

Frankfurt, , Germany

Study Site 06

München, , Germany

Study Site 02

Ratingen, , Germany

Study Site 01

Zerbst, , Germany

Study Site 03

Balatonfüred, , Hungary

Study Site 02

Budapest, , Hungary

Study Site 04

Budapest, , Hungary

Study Site 05

Budapest, , Hungary

Study Site 06

Gyula, , Hungary

Study Site 01

Veszprém, , Hungary

Study Site 01

Kaunas, , Lithuania

Study Site 02

Vilnius, , Lithuania

Study Site 06

León, Guanajuato, Mexico

Study Site 05

Mexico City, Mexico City, Mexico

Study Site 08

Mexico City, Mexico City, Mexico

Study Site 02

Chihuahua City, , Mexico

Study Site 03

Distrito Federal, , Mexico

Study Site 08

Bialystok, , Poland

Study Site 05

Bydgoszcz, , Poland

Study Site 10

Elblag, , Poland

Study Site 04

Gdynia, , Poland

Study Site 02

Katowice, , Poland

Study Site 03

Krakow, , Poland

Study Site 06

Krakow, , Poland

Study Site 09

Poznan, , Poland

Study Site 01

Warsaw, , Poland

Study Site 07

Warsaw, , Poland

Study Site 08

Kemerovo, , Russia

Study Site 11

Kemerovo, , Russia

Study Site 04

Kursk, , Russia

Study Site 03

Moscow, , Russia

Study Site 07

Moscow, , Russia

Study Site 10

Moscow, , Russia

Study Site 05

Omsk, , Russia

Study Site 09

Saratov, , Russia

Study Site 06

Smolensk, , Russia

Study Site 01

Tomsk, , Russia

Study Site 02

Yaroslavl, , Russia

Study Site 01

Belgrade, , Serbia

Study Site 02

Belgrade, , Serbia

Study Site 04

Belgrade, , Serbia

Study Site 03

Niška Banja, , Serbia

Study Site 03

Bratislava, , Slovakia

Study Site 04

Kosice - Saca, , Slovakia

Study Site 05

Lučenec, , Slovakia

Study Site 02

Považská Bystrica, , Slovakia

Study Site 01

Rimavská Sobota, , Slovakia

Study Site 08

Donetsk, , Ukraine

Study Site 01

Kharkiv, , Ukraine

Study Site 02

Kharkiv, , Ukraine

Study Site 03

Kyiv, , Ukraine

Study Site 04

Kyiv, , Ukraine

Study Site 05

Vinnytsia, , Ukraine

Study Site 06

Vinnytsia, , Ukraine

Study Site 07

Vinnytsia, , Ukraine

Study Site 09

Zaporizhzhia, , Ukraine

Countries

United States; Bulgaria; Canada; Czechia; Estonia; Germany; Hungary; Lithuania; Mexico; Poland; Russia; Serbia; Slovakia; Ukraine

References

van Vollenhoven RF, Keystone EC, Strand V, Pacheco-Tena C, Vencovsky J, Behrens F, Racewicz A, Zipp D, Rharbaoui F, Wolter R, Knierim L, Schmeidl R, Zhou X, Aigner S, Dalken B, Wartenberg-Demand A; TREAT2b study team. Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial. Ann Rheum Dis. 2018 Apr;77(4):495-499. doi: 10.1136/annrheumdis-2017-212478. Epub 2018 Jan 17.

Reference Type: DERIVED

PMID: 29343509 (View on PubMed)

Other Identifiers

2013-000114-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BT986

Identifier Type: OTHER

Identifier Source: secondary_id

986_TREAT 2b

Identifier Type: -

Identifier Source: org_study_id