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

Rheumatoid Arthritis Clinical Trial

— 986  

Official 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01999192
• Other study ID #: 986_TREAT 2b
• Secondary ID: 2013-000114-38BT
• Status: Terminated
• Phase: Phase 2
• First received: November 17, 2013
• Last updated: January 11, 2016
• Start date: October 2013
• Est. completion date: July 2015

Study information

• Verified date: January 2016
• Source: Biotest
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Paul-Ehrlich-InstitutBulgaria: Bulgarian Drug AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlEstonia: The State Agency of MedicineHungary: National Institute of PharmacyLithuania: State Medicine Control Agency - Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of Health of the Russian FederationSerbia: Medicines and Medical Devices AgencySlovakia: State Institute for Drug ControlUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 321
• Est. completion date: July 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tregalizumab

• Placebo

Locations

Country	Name	City	State
Bulgaria	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
Canada	Study Site 02	Rimouski	Quebec
Canada	Study Site 01	St-Jérôme	Quebec
Czech Republic	Study Site 03	Bruntal
Czech Republic	Study Site 05	Ostrava
Czech Republic	Study Site 01	Praha
Czech Republic	Study Site 04	Praha
Czech Republic	Study Site 08	Praha
Czech Republic	Study Site 09	Praha
Czech Republic	Study Site 02	Uherske Hradiste
Czech Republic	Study Site 07	Uherske Hradiste
Czech Republic	Study Site 06	Zlin
Estonia	Study Site 01	Tallinn
Germany	Study Site 03	Berlin
Germany	Study Site 04	Frankfurt
Germany	Study Site 06	Muenchen
Germany	Study Site 02	Ratingen
Germany	Study Site 01	Zerbst
Hungary	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	Veszprem
Lithuania	Study Site 01	Kaunas
Lithuania	Study Site 02	Vilnus
Mexico	Study Site 02	Chihuahua
Mexico	Study Site 03	Distrito Federal
Mexico	Study Site 06	Leon	Guanajuato
Mexico	Study Site 05	Mexico	Distrito Federal
Mexico	Study Site 08	Mexico	Distrito Federal
Poland	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	Warszawa
Poland	Study Site 07	Warszawa
Russian Federation	Study Site 08	Kemerovo
Russian Federation	Study Site 11	Kemerovo
Russian Federation	Study Site 04	Kursk
Russian Federation	Study Site 03	Moscow
Russian Federation	Study Site 07	Moscow
Russian Federation	Study Site 10	Moscow
Russian Federation	Study Site 05	Omsk
Russian Federation	Study Site 09	Saratov
Russian Federation	Study Site 06	Smolensk
Russian Federation	Study Site 01	Tomsk
Russian Federation	Study Site 02	Yaroslavl
Serbia	Study Site 01	Belgrade
Serbia	Study Site 02	Belgrade
Serbia	Study Site 04	Belgrade
Serbia	Study Site 03	Niska Banja
Slovakia	Study Site 03	Bratislava
Slovakia	Study Site 04	Kosice - Saca
Slovakia	Study Site 05	Lucenec
Slovakia	Study Site 02	Povazska Bystrica
Slovakia	Study Site 01	Rimavska Sobota
Ukraine	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
United States	Study Site 02	Clifton	New Jersey
United States	Study Site 09	Houston	Texas
United States	Study Site 05	Jackson	Tennessee
United States	Study Site 10	Katy	Texas
United States	Study Site 03	Lincoln	Nebraska
United States	Study Site 04	North Charleston	South Carolina
United States	Study Site 07	Paradise Valley	Arizona
United States	Study Site 01	Springfield	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Biotest	AbbVie

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of pharmacokinetics	AUC, Cmax, Tmax	up to 48 weeks	No
Other	Evaluation of safety, patient reported outcomes & blood tests.		up to 48 weeks	Yes
Primary	The proportion of subjects who achieve an ACR20 at week 12 following treatment with Tregalizumab + MTX compared with subjects treated on placebo + MTX		Week 12	No
Secondary	Proportions of subjects with an ACR 20 response.		Week 24	No
Secondary	Proportions of subjects with an ACR 50 & 70 response.		Week 12 & Week 24	No
Secondary	Proportions of subjects with an Disease Activity Score DAS28 <2.6		Week 12 & Week 24	No
Secondary	Proportions of subjects with low disease activity DAS28 =3.2		Week 12 & Week 24	No
Secondary	ACR score		up to 48 weeks	No
Secondary	Simple Disease Activity Index [SDAI] =11		week 12 & 24	No
Secondary	Clinical Disease Activity Index [CDAI] =10		week 12 & 24	No
Secondary	DAS28		up to 48 weeks	No
Secondary	EULAR response		up to 48 weeks	No
Secondary	ACR score individual components		up to 48 weeks	No
Secondary	DAS28 score individual components		up to 48 weeks	No