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Sclerosis, SystemicPhase 3NCT01532869

A Study of RoActemra/Actemra (Tocilizumab) Versus Placebo in Patients With Systemic Sclerosis

A Phase 3 study testing tocilizumab [RoActemra/Actemra] in people with Sclerosis, Systemic, run by Hoffmann-La Roche at 50 sites in 5 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

This multicenter, randomized, double-blind, placebo-controlled, two-arm, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in participants with systemic sclerosis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sclerosis, Systemic
What is being tested?
tocilizumab [RoActemra/Actemra]
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
87 participants
Where
50 sitesin 5 countries
Study dates
Mar 2012to Aug 2015
Phase
Phase 3
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

  • Adult patients, >/= 18 years of age
  • Systemic sclerosis, as defined by American College of Rheumatology (1980) criteria
  • Disease duration of </= 60 months (defined as time from first non-Raynaud phenomenon manifestation)
  • >/= 15 and </= 40 mRSS units at screening
  • Active disease, as defined by protocol
  • Uninvolved skin at injection sites
  • Negative pregnancy test for a female subject of childbearing potential

Who cannot join

  • Major surgery (including joint surgery) within 8 weeks prior to and/or during study enrollment
  • Rheumatic autoimmune disease other than systemic sclerosis
  • Skin thickening (scleroderma) limited to areas distal to the elbows or knees at screening
  • Previous treatment with tocilizumab
  • History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
  • Severe cardiopulmonary disease
Show all 10Show fewer
  • Known active current or history of recurrent infections
  • Use of any investigational, biologic, or immunosuppressive therapies including intra-articular or parenteral corticosteroids prior to study enrollment as specified in the protocol
  • As specified in the protocol, any current or past medical condition or medical history involving but not limited to the nervous, renal, pulmonary, endocrine, and gastrointestinal organ systems determined by the Principal Investigator to pose a significant safety risk to any subject while participating in the study
  • Primary or secondary immunodeficiency

Trial locations and contacts

50 sites in 5 countries.

50 sites in 5 countries

United States21 sites

  • Study site

    Ann Arbor, Michigan, 48109-0934

  • Study site

    Baltimore, Maryland, 21224

  • Study site

    Boston, Massachusetts, 02118

  • Study site

    Charleston, South Carolina, 29425

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Cleveland, Ohio, 44195

  • Study site

    Farmington, Connecticut, 06030

  • Study site

    Houston, Texas, 77030

  • Study site

    Lake Success, New York, 11042

  • Study site

    Los Angeles, California, 90025

  • Study site

    New Brunswick, New Jersey, 08903

  • Study site

    New York, New York, 10021

  • Study site

    Oklahoma City, Oklahoma, 73103

  • Study site

    Philadelphia, Pennsylvania, 19131

  • Study site

    Pittsburgh, Pennsylvania, 15261

  • Study site

    Salt Lake City, Utah, 84132

  • Study site

    San Diego, California, 44122

  • Study site

    Seattle, Washington, 98104

  • Study site

    Stanford, California, 94305-5317

  • Study site

    Toledo, Ohio, 43614

  • Study site

    Washington D.C., District of Columbia, 20007

Other trials in United States

Germany11 sites

  • Study site

    Bad Nauheim, 61231

  • Study site

    Baden-Baden, 76530

  • Study site

    Berlin, 10177

  • Study site

    Bochum, 44791

  • Study site

    Cologne, 50937

  • Study site

    Dresden, 01067

  • Study site

    Erlangen, 91054

  • Study site

    Frankfurt, 60528

  • Study site

    Hamburg, 22763

  • Study site

    Tübingen, 72076

  • Study site

    Ulm, 89081

Other trials in Germany

United Kingdom9 sites

  • Study site

    Cannock, WS11 5XY

  • Study site

    Dundee, DD1 9SY

  • Study site

    Edinburgh, EH4 2XU

  • Study site

    Leeds, LS7 4SA

  • Study site

    Liverpool, L9 7AL

  • Study site

    London, NW3 2QG

  • Study site

    Middlesbrough, TS4 3BW

  • Study site

    Newcastle upon Tyne, NE7 7DN

  • Study site

    Romford, RM7 0AG

Other trials in United Kingdom

France6 sites

  • Study site

    Bordeaux, 33075

  • Study site

    Caen, 14033

  • Study site

    Lille, 59037

  • Study site

    Paris, 75679

  • Study site

    Strasbourg, 67091

  • Study site

    Toulouse, 31000

Other trials in France

Canada3 sites

  • Study site

    London, Ontario, N6A 4V2

  • Study site

    Montreal, Quebec, H3T 1E2

  • Study site

    Toronto, Ontario, M5G 1X5

Other trials in Canada

About this study

Official title: A Phase II/III, Multicenter, Randomized, Double-blind, Placebo-controlled Study To Assess The Efficacy And Safety Of Tocilizumab Versus Placebo In Patients With Systemic Sclerosis

This multicenter, randomized, double-blind, placebo-controlled, two-arm, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in participants with systemic sclerosis. Participants will be randomized to receive either RoActemra/Actemra 162 mg subcutaneously weekly or placebo for 48 weeks. From Week 48 to Week 96, all participants will receive open-label RoActemra/Actemra 162 mg subcutaneously weekly. Anticipated time on study treatment is 96 weeks.

Being tested
Placebo, tocilizumab [RoActemra/Actemra]
Medical subject headings
Scleroderma, Systemic

What participants receive

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

  • PlaceboDrug

    Subcutaneously weekly, Weeks 0-48

  • tocilizumab [RoActemra/Actemra]Drug

    162 mg subcutaneously weekly, Weeks 0-48

  • tocilizumab [RoActemra/Actemra]Drug

    162 mg subcutaneously weekly, Week 48-96

Study groups in NCT01532869
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo; Drug: tocilizumab [RoActemra/Actemra]
TocilizumabExperimentalNot described
Receives: Drug: tocilizumab [RoActemra/Actemra]

What is being measured

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

  1. Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24

    Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.

    Measured: Baseline, Week 24

  2. Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 8 after last dose that were absent before treatment or that worsened relative to pretreatment state.

    Measured: Week 48

Secondary outcomes (13)

  1. Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI)

    SHAQ-DI assessed five scleroderma-specific visual analogue scale (VAS) items to explore the impact of participant's disease. These items were developed to measure the effect of scleroderma on five elements of disease that could have a great impact on a participant's daily activities. Each VAS item was rated separately (0-100 millimeters [mm]), with higher scores indicating more severe disease. The five items were: 1) intestinal disease, 2) breathing problem, 3) Raynaud syndrome, 4) finger ulcers, and 5) overall disease.

    Measured: Baseline, Weeks 24 and 48

  2. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48

    The HAQ-DI scale consisted of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The total score indicated the participant's self-assessed level of disability. There are four possible responses for each component: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The HAQ-DI was the sum of the domain scores, divided by the number of domains that have a score (i.e. the average score), with total range of 0 to 3, higher scores showing larger functional limitation.

    Measured: Baseline, Weeks 24 and 48

  3. Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48

    The Clinician's Global Assessment evaluated the overall impact of SSc on the participant as assessed by the physician on a VAS with scores ranging from 0 to 100 mm, with higher scores indicating worse disease in terms of severity, damage, or overall disease, but there was no standardization for the scale.

    Measured: Baseline, Weeks 24 and 48

  4. Change From Baseline in Patient's Global Assessment at Week 24 and Week 48

    The Patient's Global Assessment was a patient's reported outcome that represented the participant's overall assessment of his or her current SSc on a 100 mm horizontal VAS scale (0 mm to 100 mm), with higher scores indicating worsening disease.

    Measured: Baseline, Weeks 24 and 48

  5. Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48

    This FACIT-Fatigue Scale was a 13-item measure with participants scoring each item on a 5-point scale (0 to 4) up to 52 points. The endpoint measured was fatigue. On this scale, a numerical increase indicated an improvement in the participant's condition.

    Measured: Baseline, Weeks 24 and 48

  6. Change From Baseline in 5-D Itch Scale at Week 24 and Week 48

    The 5-D Itch Scale contained five domains of duration, degree, direction, disability, and distribution. The endpoint of the scale was pruritus. Each domain was scored on a 5-point scale, the scores of each of the five domains were achieved separately and then summed together to obtain a total 5-D score. 5-D scores ranged between 5 (no pruritus) and 25 (most severe pruritus).

    Measured: Baseline, Weeks 24 and 48

  7. Change From Baseline in mRSS at Week 48

    Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.

    Measured: Baseline, Week 48

  8. Percentage of Participants Who Maintained or Improved in mRSS From Week 24 to Week 48

    Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement. Percentage of participants with an improvement in mRSS at Week 24 (change from baseline <0) that maintained or further improved at Week 48 were reported as "Yes" and "No" with Yes = improvers at week 24 that had a change from baseline in mRSS at Week 48 <= change from baseline at Week 24.

    Measured: Week 48

  9. Change From Baseline in Tender Joint Count 28 (TJC28)

    Joint tenderness was evaluated as per assessment of 28 joints. Joints on both sides of the body, including shoulders, elbows, wrists, 10 metacarpal phalangeal (MCP) joints, 10 proximal interphalangeal joint (PIP) joints, and both knees, were assessed. Joints were classified as not tender = 0 or tender = 1. Observed data was presented for this outcome measure.

    Measured: Baseline, Weeks 3, 8, 16, 24, 32, 40, and 48

  10. Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168)

    AUC was a measure of the serum concentration of the drug over time which was measured in micrograms times (*) hour per milliliters (µg*hr/mL). It is used to characterize drug absorption.

    Measured: Pre-dose, 24, 48, 72, 96, 120 or 144, and 168 hours post dose for Baseline and Week 16

  11. Mean Serum Concentrations of Interleukin (IL)-6 by Visit

    Observed data was presented for this outcome measure.

    Measured: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48

  12. Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit

    Observed data was presented for this outcome measure.

    Measured: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48

  13. Percentage of Participants With Anti-Tocilizumab Antibody

    Measured: Baseline, and post-baseline (up to Week 48)

Timeline

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

  1. First posted15 Feb 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionJan 2014
  4. Study completionAug 2015

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01532869
Sponsor's protocol ID
WA27788
Other IDs
2011-001460-22
Status last verified
Aug 2016
First submitted
10 Feb 2012
Last updated
23 Sep 2016
Data monitoring committee
Yes

Publications

  • Gao X, Jia G, Guttman A, DePianto DJ, Morshead KB, Sun KH, Ramamoorthi N, Vander Heiden JA, Modrusan Z, Wolters PJ, Jahreis A, Arron JR, Khanna D, Ramalingam TR. Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis. Cell Rep Med. 2020 Nov 17;1(8):100140. doi: 10.1016/j.xcrm.2020.100140. eCollection 2020 Nov 17.

    PubMed 33294861

  • Stifano G, Sornasse T, Rice LM, Na L, Chen-Harris H, Khanna D, Jahreis A, Zhang Y, Siegel J, Lafyatis R. Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol. 2018 Jun;70(6):912-919. doi: 10.1002/art.40455.

    PubMed 29858547

  • Denton CP, Ong VH, Xu S, Chen-Harris H, Modrusan Z, Lafyatis R, Khanna D, Jahreis A, Siegel J, Sornasse T. Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis. Ann Rheum Dis. 2018 Sep;77(9):1362-1371. doi: 10.1136/annrheumdis-2018-213031. Epub 2018 May 31.

    PubMed 29853453

  • Khanna D, Denton CP, Lin CJF, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, Allanore Y, Pope JE, Riemekasten G, Steen V, Muller-Ladner U, Spotswood H, Burke L, Siegel J, Jahreis A, Furst DE. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018 Feb;77(2):212-220. doi: 10.1136/annrheumdis-2017-211682. Epub 2017 Oct 24.

    PubMed 29066464

  • Khanna D, Denton CP, Jahreis A, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, Allanore Y, Pope JE, Riemekasten G, Steen V, Muller-Ladner U, Lafyatis R, Stifano G, Spotswood H, Chen-Harris H, Dziadek S, Morimoto A, Sornasse T, Siegel J, Furst DE. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet. 2016 Jun 25;387(10038):2630-2640. doi: 10.1016/S0140-6736(16)00232-4. Epub 2016 May 5.

    PubMed 27156934

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing tocilizumab [RoActemra/Actemra] in people with Sclerosis, Systemic, run by Hoffmann-La Roche at 50 sites in 5 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 7 inclusion and 10 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 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in United States, Germany, United Kingdom, France, Canada. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 5 Nov 2015). 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?

Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24 (time frame: Baseline, Week 24). The study lists 2 primary outcomes in all. 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 NCT01532869, which also lists 5 linked publications.

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 Sep 2016.

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