NCT01034137

Brief Summary

This randomized, double-blind, placebo-controlled study will compare the efficacy with regard to sustained remission and safety of tocilizumab and methotrexate, in combination or as monotherapy, in treatment-naïve patients with early rheumatoid arthritis. Patients will be randomized to receive either tocilizumab (8mg/kg iv every 4 weeks) plus weekly methotrexate (po in ascending doses), or tocilizumab (8mg/kg iv every 4 weeks) plus placebo, or methotrexate plus placebo. Anticipated time on study treatment is 2 years, and target sample size is 300.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
317

participants targeted

Target at P50-P75 for phase_3 rheumatoid-arthritis

Timeline
Completed

Started Jan 2010

Longer than P75 for phase_3 rheumatoid-arthritis

Geographic Reach
1 country

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 16, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 17, 2009

Completed
15 days until next milestone

Study Start

First participant enrolled

January 1, 2010

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

July 11, 2016

Completed
Last Updated

July 11, 2016

Status Verified

June 1, 2016

Enrollment Period

4.7 years

First QC Date

December 16, 2009

Results QC Date

January 29, 2016

Last Update Submit

June 1, 2016

Conditions

Rheumatoid Arthritis

Keywords

Treat-to-target, tight control, strategy study, TCZ, MTX

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants Achieving Sustained Remission Rate At Week 104

    Sustained remission rate (SRR) is defined as Disease Activity Score 28 (DAS28) \<2.6 during ≥ 23 weeks and no more than 4 swollen joints (28 joint count) due to RA at Week 24 of remission, with the exception of up to 2 in-between DAS28 values which could be between 2.6 and 3.2. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission.

    Week 104

Secondary Outcomes (41)

  • Median Time to First Sustained Remission

    Up to Week 104

  • Mean Duration of First Sustained Remission

    Up to Week 104

  • Number of Participants Achieving Disease Activity Score 28 Remission at Weeks 12, 24, 52, and 104

    Weeks 12, 24, 52, and 104

  • Median Time to First Disease Activity Score 28 Remission

    Up to Week 104

  • Percentage of Participants With Cumulative Remission Rate at Weeks 12, 24, 52, and 104

    Weeks 12, 24, 52, and 104

  • +36 more secondary outcomes

Study Arms (3)

Tocilizumab + Methotrexate

EXPERIMENTAL

Participants will receive intravenous (IV) TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + oral capsules of MTX 10-30 mg/week in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week. The weekly dose of MTX will be taken on one particular day of the week.

Drug: methotrexateDrug: tocilizumab [RoActemra/Actemra]

Tocilizumab + Placebo Methotrexate

ACTIVE COMPARATOR

Participants will receive IV TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + weekly oral matching placebo MTX capsules in climbing dosages. The weekly dose of placebo MTX will be taken on one particular day of the week.

Drug: placebo MTXDrug: tocilizumab [RoActemra/Actemra]

Methotrexate + Placebo Tocilizumab

ACTIVE COMPARATOR

Participants will receive weekly oral MTX in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week + matching placebo TCZ IV 8 mg/kg every four week for a maximum of 26 infusions. The weekly dose of MTX will be taken on one particular day of the week.

Drug: methotrexateDrug: placebo TCZ

Interventions

methotrexateDRUG

orally weekly in ascending dosages, starting at 10mg/week

Methotrexate + Placebo TocilizumabTocilizumab + Methotrexate
placebo MTXDRUG

orally weekly

Tocilizumab + Placebo Methotrexate
placebo TCZDRUG

iv every 4 weeks

Methotrexate + Placebo Tocilizumab
tocilizumab [RoActemra/Actemra]DRUG

8mg/kg iv every 4 weeks

Tocilizumab + MethotrexateTocilizumab + Placebo Methotrexate

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • adult patients, \>/=18 years of age
  • early rheumatoid arthritis (disease symptoms \<1 year) according to ACR criteria
  • disease activity DAS28 \>2.6
  • body weight \</=110kg, BMI \</=36

You may not qualify if:

  • rheumatic autoimmune disease other than RA
  • current inflammatory joint disease other than RA
  • previous treatment with any DMARD or biologic drug used in the treatment of RA
  • intra-articular, parenteral or oral glucocorticoids used for the arthritis

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Unknown Facility

Alkmaar, 1815 JD, Netherlands

Location

Unknown Facility

Amersfoort, 3818 ES, Netherlands

Location

Unknown Facility

Amsterdam, 1056 AB, Netherlands

Location

Unknown Facility

Apeldoorn, 7300 DS, Netherlands

Location

Unknown Facility

Breda, 4819 EV, Netherlands

Location

Unknown Facility

Den Helder, 1782GZ, Netherlands

Location

Unknown Facility

Emmeloord, 8300 GA, Netherlands

Location

Unknown Facility

Gorinchem, 4204 AA, Netherlands

Location

Unknown Facility

Gouda, 2803 HH, Netherlands

Location

Unknown Facility

Groningen, 9700RB, Netherlands

Location

Unknown Facility

Haarlem, 2035 RC, Netherlands

Location

Unknown Facility

Heerlen, 6419 PC, Netherlands

Location

Unknown Facility

Hilversum, 1213 HX, Netherlands

Location

Unknown Facility

Hoofddorp, 2134 TM, Netherlands

Location

Unknown Facility

Leeuwarden, 8934 AD, Netherlands

Location

Unknown Facility

Leiden, 2333 ZA, Netherlands

Location

Unknown Facility

Nieuwegein, 3430 EM, Netherlands

Location

Unknown Facility

Nijmegen, 6522 JV, Netherlands

Location

Unknown Facility

Sneek, 8601 ZK, Netherlands

Location

Unknown Facility

Utrecht, 3584 CX, Netherlands

Location

Unknown Facility

Woerden, 3447 GN, Netherlands

Location

Related Publications (7)

  • Gosselt HR, Verhoeven MMA, de Rotte MCFJ, Pluijm SMF, Muller IB, Jansen G, Tekstra J, Bulatovic-Calasan M, Heil SG, Lafeber FPJG, Hazes JMW, de Jonge R. Validation of a Prognostic Multivariable Prediction Model for Insufficient Clinical Response to Methotrexate in Early Rheumatoid Arthritis and Its Clinical Application in Evidencio. Rheumatol Ther. 2020 Dec;7(4):837-850. doi: 10.1007/s40744-020-00230-7. Epub 2020 Sep 14.

    PMID: 32926395DERIVED

  • Teitsma XM, Yang W, Jacobs JWG, Petho-Schramm A, Borm MEA, Harms AC, Hankemeier T, van Laar JM, Bijlsma JWJ, Lafeber FPJG. Baseline metabolic profiles of early rheumatoid arthritis patients achieving sustained drug-free remission after initiating treat-to-target tocilizumab, methotrexate, or the combination: insights from systems biology. Arthritis Res Ther. 2018 Oct 15;20(1):230. doi: 10.1186/s13075-018-1729-2.

    PMID: 30322408DERIVED

  • Teitsma XM, Jacobs JWG, Welsing PMJ, de Jong PHP, Hazes JMW, Weel AEAM, Petho-Schramm A, Borm MEA, van Laar JM, Lafeber FPJG, Bijlsma JWJ. Inadequate response to treat-to-target methotrexate therapy in patients with new-onset rheumatoid arthritis: development and validation of clinical predictors. Ann Rheum Dis. 2018 Sep;77(9):1261-1267. doi: 10.1136/annrheumdis-2018-213035. Epub 2018 May 14.

    PMID: 29760159DERIVED

  • Teitsma XM, Jacobs JWG, Welsing PMJ, Petho-Schramm A, Borm MEA, van Laar JM, Lafeber FPJG, Bijlsma JWJ. Radiographic joint damage in early rheumatoid arthritis patients: comparing tocilizumab- and methotrexate-based treat-to-target strategies. Rheumatology (Oxford). 2018 Feb 1;57(2):309-317. doi: 10.1093/rheumatology/kex386.

    PMID: 29095992DERIVED

  • Teitsma XM, Jacobs JWG, Welsing PMJ, Petho-Schramm A, Borm MEA, Hendriks L, Denissen NHAM, van Laar JM, Lafeber FPJG, Bijlsma JWJ. Patient-reported outcomes in newly diagnosed early rheumatoid arthritis patients treated to target with a tocilizumab- or methotrexate-based strategy. Rheumatology (Oxford). 2017 Dec 1;56(12):2179-2189. doi: 10.1093/rheumatology/kex319.

    PMID: 29029185DERIVED

  • Teitsma XM, Jacobs JWG, Mokry M, Borm MEA, Petho-Schramm A, van Laar JM, Bijlsma JWJ, Lafeber FPJ. Identification of differential co-expressed gene networks in early rheumatoid arthritis achieving sustained drug-free remission after treatment with a tocilizumab-based or methotrexate-based strategy. Arthritis Res Ther. 2017 Jul 20;19(1):170. doi: 10.1186/s13075-017-1378-x.

    PMID: 28728565DERIVED

  • Bijlsma JWJ, Welsing PMJ, Woodworth TG, Middelink LM, Petho-Schramm A, Bernasconi C, Borm MEA, Wortel CH, Ter Borg EJ, Jahangier ZN, van der Laan WH, Bruyn GAW, Baudoin P, Wijngaarden S, Vos PAJM, Bos R, Starmans MJF, Griep EN, Griep-Wentink JRM, Allaart CF, Heurkens AHM, Teitsma XM, Tekstra J, Marijnissen ACA, Lafeber FPJ, Jacobs JWG. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016 Jul 23;388(10042):343-355. doi: 10.1016/S0140-6736(16)30363-4. Epub 2016 Jun 7.

    PMID: 27287832DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexatetocilizumab

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

AminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Roche Trial Information Hotline
Organization
F. Hoffmann-La Roche AG
global.trial_information@roche.com
+41 616878333

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 16, 2009

First Posted

December 17, 2009

Study Start

January 1, 2010

Primary Completion

September 1, 2014

Study Completion

September 1, 2014

Last Updated

July 11, 2016

Results First Posted

July 11, 2016

Record last verified: 2016-06

Data Sharing

IPD Sharing
Will share

Locations

NL(21)