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

NCT01999192 | Terminated Phase 2 Results DMC

• 3 other identifiers: 986_TREAT 2b2013-000114-38BT986
• Study Type: interventional
• Target: 321
• Locations: 14 countries
• Sites: 84

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.

Conditions

Rheumatoid Arthritis

Keywords

inadequate response to MTX; Methotrexate; rheumatoid Arthritis; Phase 2b

Outcome Measures

Primary Outcomes (1)

• The Proportion of Subjects Who Achieve an ACR20 at Week 12 Following Treatment With Tregalizumab + MTX Compared With Subjects Treated on Placebo + MTX

  The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS.

  Week 12

Secondary Outcomes (11)

• Proportions of Subjects With an ACR 20 Response.

  Week 24

• Proportions of Subjects With an ACR 50 & 70 Response.

  Week 12 & Week 24

• Proportions of Subjects With an Disease Activity Score DAS28 <2.6

  Week 12 & Week 24

• Proportions of Subjects With Low Disease Activity DAS28 ≤3.2

  Week 12 & Week 24

• ACR Score

  up to 48 weeks

Other Outcomes (2)

• Pharmacokinetics

  up to 48 weeks

• Evaluation of Safety, Patient Reported Outcomes & Blood Tests.

  up to 48 weeks

Study Arms (4)

Dose Level 1 Tregalizumab

EXPERIMENTAL

25mg Tregalizumab s.c. weekly

Drug: Tregalizumab

Dose Level 2 Tregalizumab

EXPERIMENTAL

100mg Tregalizumab s.c. weekly

Drug: Tregalizumab

Dose Level 3 Tregalizumab

EXPERIMENTAL

200mg Tregalizumab s.c. weekly

Drug: Tregalizumab

Placebo

PLACEBO COMPARATOR

Placebo s.c. weekly

Drug: Placebo

Interventions

Tregalizumab DRUG

humanized anti-CD4 mAb

Also known as: BT061

Dose Level 1 Tregalizumab; Dose Level 2 Tregalizumab; Dose Level 3 Tregalizumab

Placebo DRUG

identical end formulation buffer

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• Subject is ≥18 and ≤75 years of age.
• Subject has a body mass index ≥18 and ≤35 kg/m².
• Subject receives treatment with corticosteroids ≤10 mg prednisone equivalent, stable for at least 4 weeks prior to baseline and during the study, if applicable.
• 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.
• Female subjects of childbearing potential: has both a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
• 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).
• Subject has a cluster of differentiation 4 (CD4) cell count of \> 400/µl at screening.

You may not qualify if:

• 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.
• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Biotest: lead
• AbbVie: collaborator

Study Sites (84)

Study Site 07

Paradise Valley, Arizona, 85253, United States

Location

Study Site 01

Springfield, Illinois, 62704, United States

Location

Study Site 03

Lincoln, Nebraska, 68516, United States

Location

Study Site 02

Clifton, New Jersey, 07012, United States

Location

Study Site 04

North Charleston, South Carolina, 29406, United States

Location

Study Site 05

Jackson, Tennessee, 38305, United States

Location

Study Site 09

Houston, Texas, 77004, United States

Location

Study Site 10

Katy, Texas, 77450, United States

Location

Study Site 01

Plovdiv, Bulgaria

Location

Study Site 06

Plovdiv, Bulgaria

Location

Study Site 02

Sofia, Bulgaria

Location

Study Site 04

Sofia, Bulgaria

Location

Study Site 07

Sofia, Bulgaria

Location

Study Site 05

Stara Zagora, Bulgaria

Location

Study Site 03

Varna, Bulgaria

Location

Study Site 02

Rimouski, Quebec, Canada

Location

Study Site 01

Saint-Jérôme, Quebec, Canada

Location

Study Site 03

Bruntál, Czechia

Location

Study Site 05

Ostrava, Czechia

Location

Study Site 01

Prague, Czechia

Location

Study Site 04

Prague, Czechia

Location

Study Site 08

Prague, Czechia

Location

Study Site 09

Prague, Czechia

Location

Study Site 02

Uherské Hradiště, Czechia

Location

Study Site 07

Uherské Hradiště, Czechia

Location

Study Site 06

Zlín, Czechia

Location

Study Site 01

Tallinn, Estonia

Location

Study Site 03

Berlin, Germany

Location

Study Site 04

Frankfurt, Germany

Location

Study Site 06

München, Germany

Location

Study Site 02

Ratingen, Germany

Location

Study Site 01

Zerbst, Germany

Location

Study Site 03

Balatonfüred, Hungary

Location

Study Site 02

Budapest, Hungary

Location

Study Site 04

Budapest, Hungary

Location

Study Site 05

Budapest, Hungary

Location

Study Site 06

Gyula, Hungary

Location

Study Site 01

Veszprém, Hungary

Location

Study Site 01

Kaunas, Lithuania

Location

Study Site 02

Vilnius, Lithuania

Location

Study Site 06

León, Guanajuato, Mexico

Location

Study Site 05

Mexico City, Mexico City, Mexico

Location

Study Site 08

Mexico City, Mexico City, Mexico

Location

Study Site 02

Chihuahua City, Mexico

Location

Study Site 03

Distrito Federal, Mexico

Location

Study Site 08

Bialystok, Poland

Location

Study Site 05

Bydgoszcz, Poland

Location

Study Site 10

Elblag, Poland

Location

Study Site 04

Gdynia, Poland

Location

Study Site 02

Katowice, Poland

Location

Study Site 03

Krakow, Poland

Location

Study Site 06

Krakow, Poland

Location

Study Site 09

Poznan, Poland

Location

Study Site 01

Warsaw, Poland

Location

Study Site 07

Warsaw, Poland

Location

Study Site 08

Kemerovo, Russia

Location

Study Site 11

Kemerovo, Russia

Location

Study Site 04

Kursk, Russia

Location

Study Site 03

Moscow, Russia

Location

Study Site 07

Moscow, Russia

Location

Study Site 10

Moscow, Russia

Location

Study Site 05

Omsk, Russia

Location

Study Site 09

Saratov, Russia

Location

Study Site 06

Smolensk, Russia

Location

Study Site 01

Tomsk, Russia

Location

Study Site 02

Yaroslavl, Russia

Location

Study Site 01

Belgrade, Serbia

Location

Study Site 02

Belgrade, Serbia

Location

Study Site 04

Belgrade, Serbia

Location

Study Site 03

Niška Banja, Serbia

Location

Study Site 03

Bratislava, Slovakia

Location

Study Site 04

Kosice - Saca, Slovakia

Location

Study Site 05

Lučenec, Slovakia

Location

Study Site 02

Považská Bystrica, Slovakia

Location

Study Site 01

Rimavská Sobota, Slovakia

Location

Study Site 08

Donetsk, Ukraine

Location

Study Site 01

Kharkiv, Ukraine

Location

Study Site 02

Kharkiv, Ukraine

Location

Study Site 03

Kyiv, Ukraine

Location

Study Site 04

Kyiv, Ukraine

Location

Study Site 05

Vinnytsia, Ukraine

Location

Study Site 06

Vinnytsia, Ukraine

Location

Study Site 07

Vinnytsia, Ukraine

Location

Study Site 09

Zaporizhzhia, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 29343509 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tregalizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Due to the lack of efficacy the Extension Phase of the study was terminated early.

Results Point of Contact

• Title: Xuefei Zhou Manager Strategy & Development
• Organization: Biotest AG

xuefei_zhou@biotest.de

+496103801

Study Officials

• Ronald van Vollenhoven, Prof. MD

  Karolinska Universitetssjukhuset, Solna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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 17, 2013
• First Posted: December 3, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 24, 2017
• Results First Posted: August 24, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

RU (11); SL (5); UA (9); BU (7); SE (4); CZ (9); HU (6); US (8); ES (1); CA (2); DE (5); ME (5); PL (10); LI (2)