A Study of Subcutaneous (SC) Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis (RA) and Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

NCT02046616 | Completed Phase 3 Results

• 2 other identifiers: ML286912013-002007-34
• Study Type: interventional
• Target: 133
• Locations: 4 countries
• Sites: 27

Brief Summary

This Phase IIIb, open-label, single-arm study will evaluate the safety, efficacy, and tolerability of SC tocilizumab (RoActemra/Actemra) in monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active RA who are naive to tocilizumab. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously weekly (QW) for 24 weeks.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12

  CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.

  Baseline, Week 12

Secondary Outcomes (16)

• Change From Baseline in Disease Activity Score 28 (DAS28)-Erythrocyte Sedimentation Rate (ESR) Score

  Baseline and Weeks 2, 4, 8, 12, 16, 20, 24

• Percentage of Participants With American College of Rheumatology (ACR) Response

  Weeks 2, 4, 8, 12, 16, 20, 24

• Percentage of Participants With European League Against Rheumatism (EULAR) Response

  Weeks 2, 4, 8, 12, 16, 20, 24

• Change From Baseline in CDAI at Weeks 2, 4, 8, 16, 20, and 24

  Baseline and Weeks 2, 4, 8, 16, 20, 24

• Change From Baseline in Simplified Disease Activity Index (SDAI)

  Baseline and Weeks 2, 4, 8, 12, 16, 20, 24

Study Arms (1)

Tocilizumab Alone or Combined with Methotrexate or Other DMARD

EXPERIMENTAL

All participants will receive tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs, irrespective of body weight, for 24 weeks.

Drug: Tocilizumab; Drug: Methotrexate; Drug: Non-Biologic DMARDs

Interventions

Tocilizumab DRUG

Tocilizumab 162 mg will be administered subcutaneously QW.

Also known as: RoActemra, Actemra

Tocilizumab Alone or Combined with Methotrexate or Other DMARD

Methotrexate DRUG

Methotrexate dosing is not specified by the protocol and will be given as per standard practice. Participants must be at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab Alone or Combined with Methotrexate or Other DMARD

Non-Biologic DMARDs DRUG

Participants will receive non-biologic DMARDs (same non-biologic DMARD that participant was receiving at time of study entry). Dosing is not specified by the protocol and will be given as per standard practice. Participants must be at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab Alone or Combined with Methotrexate or Other DMARD

Eligibility Criteria

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

You may qualify if:

• Active RA according to the revised ACR (1987) criteria or EULAR/ACR (2010) criteria
• Moderate to severe RA with a DAS28-ESR score \>3.2 points
• Inadequate response and/or intolerance to MTX or other non-biologic DMARDs and/or where MTX or other non-biologic DMARDs are inappropriate
• Oral corticosteroids (less than or equal to \[\</=\] 10 mg per day prednisolone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) permitted if on stable dose regimen for greater than or equal to \[\>/=\] 4 weeks prior to baseline
• Permitted non-biologic DMARDs allowed if at stable dose for \>/=4 weeks prior to baseline
• Receiving treatment on an outpatient basis, not including tocilizumab
• Agreement to use reliable means of contraception as defined by protocol, among females of childbearing potential and males with female partners of childbearing potential

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
• Rheumatic autoimmune disease other than RA
• Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
• Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
• Prior history of or current inflammatory joint disease other than RA
• Exposure to tocilizumab or any other biologic DMARDs at any time prior to baseline
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
• Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Evidence of serious concomitant disease or disorder
• Known active current or history of recurrent infection
• Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
• Active tuberculosis requiring treatment within the previous 3 years
• Positive for hepatitis B or hepatitis C
• History of or current active primary or secondary immunodeficiency

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (27)

Aalborg Universitetshospital Nord, Reumatologisk Afdeling

Aalborg, 9000, Denmark

Location

Glostrup Hospital, Reumatologisk Afdeling, Ambulatoriet

Glostrup Municipality, 2600, Denmark

Location

Gentofte Hospital, Medicinsk Afd. C, Klinik for Gigt- og Rygsygdomme

Hellerup, 2900, Denmark

Location

Holbæk Sygehus, Medicinsk Afd., Reumatologisk Amb.15-2

Holbæk, 4300, Denmark

Location

Sjællands Universitetshospital, Køge; Reumatologisk Afdeling

Køge, 4600, Denmark

Location

Odense Universitetshospital, Reumatologisk Afdeling C, Ambulatoriet

Odense, 5000, Denmark

Location

Svendborg Sygehus, Reumatologisk Ambulatorium

Svendborg, 5700, Denmark

Location

Helsinki University Central Hospital; Rheumatology Clinic

Helsinki, 00290, Finland

Location

Kiljavan Lääketutkimus Oy

Hyvinkää, 05800, Finland

Location

Central Hospital of Pohjois-Karjala; Outpatient Clinic of Rheumatology

Joensuu, 80210, Finland

Location

Keski-Suomen Keskussairaala; Sisätautien Klinikka

Jyväskylä, 40620, Finland

Location

Lappeenranta Central Hospital; Outpatient Clinic of Internal Medicine

Lappeenranta, 53130, Finland

Location

Oulu University Hospital; Rheumatology

Oulu, 90220, Finland

Location

Ålesund Sykehus; Revmatologisk Avdeling

Ålesund, 6017, Norway

Location

Haukeland Universitetssykehus; Revmatologisk Avdeling

Bergen, 5053, Norway

Location

Drammen sykehus Vestre Viken HF, Revmatologisk avd.

Drammen, 3004, Norway

Location

Diakonhjemmet; Reumatolgisk Avdeling

Oslo, 0370, Norway

Location

St. Olavs Hospital; Revmatologisk avdeling

Trondheim, 7030, Norway

Location

Länssjukhuset Ryhov; Ortoped- och Reumatolog kliniken

Jönköping, 551 85, Sweden

Location

Uni Hospital Linkoeping; Dept. of Rheumatology

Linköping, 58185, Sweden

Location

Skånes Universitetssjukhus Lund; Reumatologkliniken

Lund, 221 85, Sweden

Location

Skånes Universitetssjukhus Malmö; Reumatologkliniken

Malmo, 205 02, Sweden

Location

Örebro Uni Hospital; Rheumatology

Örebro, 70185, Sweden

Location

Simrishamns Sjukhus

Simrishamn, 272 81, Sweden

Location

Karolinska Sjukhuset; Reumatologkliniken D2-1

Stockholm, 171 76, Sweden

Location

Akademiska sjukhuset, Reumatologkliniken

Uppsala, 75185, Sweden

Location

Västmanlands sjukhus Västerås, Reumatologkliniken

Västerås, 72189, Sweden

Location

Related Publications (4)

• Hammer HB, Jensen Hansen IM, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission. Rheumatol Adv Pract. 2021 May 14;5(2):rkab030. doi: 10.1093/rap/rkab030. eCollection 2021.

  PMID: 34131623 DERIVED

• Hammer HB, Hansen I, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis. Scand J Rheumatol. 2021 Jul;50(4):262-270. doi: 10.1080/03009742.2020.1845394. Epub 2021 Jan 19.

  PMID: 33464147 DERIVED

• Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.

  PMID: 30649524 DERIVED

• Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.

  PMID: 29244149 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Methotrexate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: January 28, 2014
• Study Start: May 28, 2014
• Primary Completion: September 13, 2016
• Study Completion: September 13, 2016
• Last Updated: April 13, 2018
• Results First Posted: April 13, 2018

Record last verified: 2018-04

Locations

DK (7); NO (5); SE (9); FI (6)