A 24-week, placebo-controlled, multicenter study to investigate the efficacy and safety of tregalizumab (BT061) in combination with methotrexate in the treatment of subjects with active rheumatoid arthritis who have had an insufficient response to methotrexate alone, followed by a 24-week extension phase: T cell REgulating Arthritis Trial 2b (TREAT 2b)

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2013-000114-38-DE
• Date of registration: 29/05/2013
• Prospective Registration: Yes
• Primary sponsor: Biotest AG
• Public title: A 24-week, placebo-controlled, multicenter study to investigate the efficacy and safety of tregalizumab (BT061) in combination with methotrexate in the treatment of subjects with active rheumatoid arthritis who have had an insufficient response to methotrexate alone, followed by a 24-week extension phase: T cell REgulating Arthritis Trial 2b (TREAT 2b)
• Scientific title: A 24-week phase IIb, randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of tregalizumab (BT061) in combination with methotrexate in the treatment of subjects with active rheumatoid arthritis who have had an inadequate response to methotrexate alone, followed by a 24-week extension phase: T cell REgulating Arthritis Trial 2b (TREAT 2b) - T cell REgulating Arthritis Trial 2b (TREAT 2b)
• Date of first enrolment: 29/11/2013
• Target sample size: 304
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000114-38
• 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: 4

Countries of recruitment

Bulgaria, Canada, Czech Republic, Estonia, Germany, Hungary, Lithuania, Mexico, Poland, Russian Federation, Serbia, Slovakia, Sweden, Ukraine, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Biotest AG

• Name: Clinical Trial Information
• Affiliation: Biotest AG

Key inclusion & exclusion 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 or 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 or 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 >0.4 × 109/L at screening.

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 243
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 61

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 erythemotosus or any arthritis with onset prior to age 17 years). However, subjects may have secondary Sjögren's syndrome.



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

Health Condition(s) or Problem(s) studied

Subjects with active rheumatoid arthritis incompletely controlled on stable MTX doses
MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Product Name: Tregalizumab
Product Code: BT061
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Tregalizumab
Current Sponsor code: BT061
Other descriptive name: A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 12.5-
INN or Proposed INN: Tregalizumab
Current Sponsor code: BT061
Other descriptive name: B
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: Tregalizumab
Current Sponsor code: BT061
Other descriptive name: C
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Tregalizumab
Current Sponsor code: BT061
Other descriptive name: D
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
INN or Proposed INN: Tregalizumab
Current Sponsor code: BT061
Other descriptive name: E
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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

Main Objective: To determine the efficacy and safety of three doses of tregalizumab administered
over 24 weeks, followed by a 24-week extension phase (active treatment only), in
combination with methotrexate (MTX), for the treatment of adult subjects with active
rheumatoid arthritis (RA) who have had an inadequate response to MTX alone
(MTX-IR).

Primary end point(s): The proportion of subjects who achieve an ACR20 at Week 12 following treatment with tregalizumab (25 mg, 100 mg or 200 mg) + MTX compared with subjects treated with placebo + MTX.

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): Proportion of subjects with an ACR20 at Week 24,
Proportion of subjects with an ACR50 at Week 12,
Proportion of subjects with an ACR50 at Week 24
Proportion of subjects with an ACR70 at Week 12
Proportion of subjects with an ACR70 at Week 24
Proportion of subjects with a Disease Activity Score (DAS)28 =2.6 at Week 12
Proportion of subjects with a DAS28 =2.6 at Week 24
Proportion of subjects with low disease activity (DAS28 =3.2, Simplified Disease Activity Index [SDAI] =11, Clinical Disease Activity Index [CDAI] =10) at Week 12
Proportion of subjects with low disease activity (DAS28 =3.2, SDAI =11, CDAI =10) at Week 24
ACR score by visit
DAS28 by visit
EULAR response by visit
ACR and DAS28 score components by visit
-TJC (68 joint count, incl. 28 joint count)
- SJC (66 joint count, incl. 28 joint count)
-CRP
-ESR
- Patient's assessment of pain (Visual Analog Scale [VAS])
- Patient's Global Assessment of Disease Activity (VAS)
- Physician Global Assessment of Disease Activity (VAS)
- Health Assessment Questionnaire Disability Index (HAQ DI)
Morning stiffness by visit
SDAI by visit
CDAI by visit
Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue by visit
Short Form (36)® Health Survey, Version 2.0 (SF 36) by visit
Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis WPAI RA by visit

Timepoint(s) of evaluation of this end point: Screening, Weeks 0, 1, 2, 4, 6, 8, 12, 16, 24, 28, 32, 40, 48 except FACIT-Fatigue, SF-36, WPAI-RA (Screening, Weeks 0, 2, 6, 12, 24, 32, 48)

Secondary ID(s)

986

Source(s) of Monetary Support

Biotest AG