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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01532869
First received: February 10, 2012
Last updated: August 2, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Sclerosis, Systemic
Drug: Placebo
Drug: tocilizumab [RoActemra/Actemra]
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) [ Time Frame: Baseline, Weeks 24 and 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48 [ Time Frame: Baseline, Weeks 24 and 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48 [ Time Frame: Baseline, Weeks 24 and 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 [ Time Frame: Baseline, Weeks 24 and 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Functional Assessment of Chronic Illness Therapy−Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48 [ Time Frame: Baseline, Weeks 24 and 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in 5-D Itch Scale at Week 24 and Week 48 [ Time Frame: Baseline, Weeks 24 and 48 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in mRSS at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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 Who Maintained or Improved in mRSS From Week 24 to Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Tender Joint Count 28 (TJC28) [ Time Frame: Baseline, Weeks 3, 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    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.

  • Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168) [ Time Frame: Pre-dose, 24, 48, 72, 96, 120 or 144, and 168 hours post dose for Baseline and Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Serum Concentrations of Interleukin (IL)-6 by Visit [ Time Frame: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48 ] [ Designated as safety issue: No ]
    Observed data was presented for this outcome measure.

  • Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit [ Time Frame: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48 ] [ Designated as safety issue: No ]
    Observed data was presented for this outcome measure.

  • Percentage of Participants With Anti-Tocilizumab Antibody [ Time Frame: Baseline, and post-baseline (up to Week 48) ] [ Designated as safety issue: No ]

Enrollment: 87
Study Start Date: March 2012
Study Completion Date: August 2015
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Subcutaneously weekly, Weeks 0-48
Drug: tocilizumab [RoActemra/Actemra]
162 mg subcutaneously weekly, Week 48-96
Experimental: Tocilizumab Drug: tocilizumab [RoActemra/Actemra]
162 mg subcutaneously weekly, Weeks 0-48
Drug: tocilizumab [RoActemra/Actemra]
162 mg subcutaneously weekly, Week 48-96

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01532869

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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01532869     History of Changes
Other Study ID Numbers: WA27788  2011-001460-22 
Study First Received: February 10, 2012
Results First Received: October 8, 2015
Last Updated: August 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 23, 2016