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Arthritis, RheumatoidPhase 2NCT00718718

A Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

A Phase 2 study testing CNTO 136 100 mg, CNTO 136 50 mg and CNTO 136 25 mg in people with Arthritis, Rheumatoid, run by Centocor, Inc. at 38 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the effectiveness and safety of subcutaneous (under the skin) administration of anti-interleukin-6 monoclonal antibody (CNTO 136) in reducing signs and symptoms of participants with active rheumatoid arthritis (RA) with methotrexate (MTX) therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
CNTO 136 100 mg, CNTO 136 50 mg and CNTO 136 25 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
187 participants
Where
38 sitesin 7 countries
Study dates
11 Aug 2008to 3 Mar 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosed with rheumatoid arthritis (RA) for at least 4 months prior to screening
  • Have been treated and having an inadequate response with the tolerated dose of methotrexate (MTX) (at least 15mg/week) for at least 4 months prior to screening. MTX doses of 10 or 12.5 mg/week are allowed if participant had intolerance of 15 mg/week
  • MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the start of the study medication
  • Have active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints, at the time of screening and baseline, and either anti-cyclic citrullinated peptide antibody-positive or rheumatoid factor positive at screening
  • C-reactive protein greater than or equal to 1.0 mg/dL (10 mg/L)
  • Agree to use one of the contraception methods defined in the protocol

Who cannot join

  • Have inflammatory diseases other than RA that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis
  • Family history of/ have long QT syndrome; or a history of second or third-degree heart block
  • Received systemic immunosuppressives or disease modifying antirheumatic drug other than MTX, sulfasalazine, hydroxychloroquine or chloroquine within 4 weeks prior to the start of study medication
  • Received intra articular (into joints), intramuscular, or intravenous corticosteroids within 4 weeks prior to the start of study medication
  • Positive human immunodeficiency virus test, hepatitis B or hepatitis C
  • History of / have chronic or recurrent infectious disease, history of / active tuberculosis
  • Have serious infection within 2 months prior to start of study medication

Trial locations and contacts

38 sites in 7 countries.

38 sites in 7 countries

United States8 sites

  • Study site

    Anderson, South Carolina

  • Study site

    Aventura, Florida

  • Study site

    Charlotte, North Carolina

  • Study site

    Duncansville, Pennsylvania

  • Study site

    Frederick, Maryland

  • Study site

    Kalamazoo, Michigan

  • Study site

    Lexington, Kentucky

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Japan8 sites

  • Study site

    Goshogawara

  • Study site

    Hitachi

  • Study site

    Kawagoe

  • Study site

    Kitakyushu

  • Study site

    Miyazaki

  • Study site

    Sasebo

  • Study site

    Shinjuku-Ku

  • Study site

    Tomigusuku

Other trials in Japan

Poland8 sites

  • Study site

    Bialystok

  • Study site

    Bydgoszcz

  • Study site

    Elblag

  • Study site

    Gdynia

  • Study site

    Krakow

  • Study site

    Lublin

  • Study site

    Poznan

  • Study site

    Warsaw

Other trials in Poland

Russia4 sites

  • Study site

    Kemerovo

  • Study site

    Moscow

  • Study site

    Novosibirsk

  • Study site

    Saint Petersburg

Other trials in Russia

South Korea4 sites

  • Study site

    Busan

  • Study site

    Daegu

  • Study site

    Daejeon

  • Study site

    Seoul

Other trials in South Korea

Hungary3 sites

  • Study site

    Budapest

  • Study site

    Győr

  • Study site

    Kecskemét

Other trials in Hungary

Mexico3 sites

  • Study site

    Guadalajara

  • Study site

    México

  • Study site

    Mexico City

Other trials in Mexico

About this study

Official title: A Phase 2, 2-Part, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Proof-of-concept, Dose-finding Study Evaluating the Efficacy and Safety of CNTO 136 Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy

The purpose of this study is to evaluate the effectiveness and safety of subcutaneous (under the skin) administration of anti-interleukin-6 monoclonal antibody (CNTO 136) in reducing signs and symptoms of participants with active rheumatoid arthritis (RA) with methotrexate (MTX) therapy.

Read the detailed description

This is a multicenter, double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study) study. This study will be conducted in 2 parts (Part A and Part B). Each part consists of 3 phases: screening (approximately 1 month prior to the start of study medication), treatment phase (Part A: 22 weeks and Part B: 24 weeks), and follow-up phase (approximately 4 months after the last administration of study medication). In Part A, participants will be randomly assigned to 2 groups to receive CNTO 136 100 mg and placebo for 22 weeks. All participants in Part A, will be crossed over at Week 12 from placebo to CNTO 136 (for Group 1) and from CNTO 136 to placebo (for Group 2). In Part B, participants will be randomly assigned to 5 groups to receive placebo and/or 1 of 3 doses of CNTO 136 (100mg, 50mg or 25mg) for 24 weeks. Participants in Part B, Group 1 will be crossed over at Week 12 from placebo to CNTO 136. All participants should be maintained on a stable dose of MTX for at least 6 weeks prior to the start of study medication through Week 24. Safety will be evaluated by the assessment of adverse events, vital signs, clinical findings, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be approximately 42 weeks.

Being tested
CNTO 136 100 mg, CNTO 136 50 mg, CNTO 136 25 mg, Placebo, Methotrexate
Keywords
Arthritis, Rheumatoid, Rheumatoid Arthritis, Active Rheumatoid Arthritis, CNTO 136, Interleukin-6, Anti-interleukin-6 monoclonal antibody, Methotrexate, Placebo
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CNTO 136 100 mgDrug

    Also called Sirukumab

    CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm.

  • CNTO 136 50 mgDrug

    Also called Sirukumab

    CNTO 136 50 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.

  • CNTO 136 25 mgDrug

    Also called Sirukumab

    CNTO 136 25 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24.

  • PlaceboDrug

    Placebo will be adminstered subcutaneously as per the appropriate randomized arm.

  • MethotrexateDrug

    Stable dose of methotrexate will be maintained through Week 24.

Study groups in NCT00718718
Study groupRoleWhat they receive
Part A, Group 1ExperimentalParticipants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate
Part A, Group 2ExperimentalParticipants will receive CNTO 136 100 mg (Week 0 to Week 10) and later placebo (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate
Part B, Group 1ExperimentalParticipants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate
Part B, Group 2ExperimentalParticipants will receive CNTO 136 100 mg (Week 0 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 100 mg; Drug: Methotrexate
Part B, Group 3ExperimentalParticipants will receive CNTO 136 100 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6, 10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 100 mg; Drug: Placebo; Drug: Methotrexate
Part B, Group 4ExperimentalParticipants will receive CNTO 136 50 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 50 mg; Drug: Placebo; Drug: Methotrexate
Part B, Group 5ExperimentalParticipants will receive CNTO 136 25 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.
Receives: Drug: CNTO 136 25 mg; Drug: Placebo; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 (Part B)

    An American College of Rheumatology (ACR) 50 response is defined as greater than or equal to (>=) 50 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: participant's assessment of pain using Visual Analogue Scale (Score) VAS (0-10 scale, 0=no pain and 10=worst possible pain), participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and serum C-reactive protein (CRP).

    Measured: Week 12

Secondary outcomes (5)

  1. Change From Baseline in Disease Activity Index Score 28 (DAS28) Based on C-reactive Protein (CRP) at Week 12 (Part A and Part B)

    The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. A negative change from baseline in DAS28 (CRP) (that is, a decrease from baseline) indicates improvement from baseline.

    Measured: Baseline, Week 12

  2. Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 12 (Part A)

    An ACR 50 response is defined as >= 50% improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP.

    Measured: Week 12

  3. Serum Sirukumab Concentrations Through Week 38 (Part A)

    Sirukumab Concentrations in serum were measured.

    Measured: Week 0, Day 2, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 10, Week 10 Day 4, Week 10 Day 7, Week 12, Week 14, Week 18, Week 22, Week 24, and Week 38

  4. Serum Sirukumab Concentrations Through Week 38 (Part B)

    Sirukumab Concentrations in serum were measured.

    Measured: Week 0, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 24 Day4, Week 24 Day7, Week 26, Week 28, Week 30, Week 34 and Week 38

  5. Percent Improvement From Baseline in Serum C-Reactive Protein (CRP) At Week 2 (Part A and Part B)

    Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement.

    Measured: Baseline, Week 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2008 (estimated)
  2. Study start11 Aug 2008
  3. Primary completion3 Mar 2011
  4. Study completion3 Mar 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
187 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00718718
Sponsor's protocol ID
CR015214
Other IDs
C1377T04, 2007-006603-20
Status last verified
Dec 2017
First submitted
17 Jul 2008
Last updated
23 Jan 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes

Publications

  • Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014 Sep;73(9):1616-25. doi: 10.1136/annrheumdis-2013-205137. Epub 2014 Apr 3.

    PubMed 24699939

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CNTO 136 100 mg, CNTO 136 50 mg and CNTO 136 25 mg in people with Arthritis, Rheumatoid, run by Centocor, Inc. at 38 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Japan, Poland, Russia, South Korea and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 (Part B) (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00718718, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.

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