Systemic Sclerosis MedDRA version: 19.0 Level: PT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age>=18 years at baseline (Day 1) - Diagnosis of SSc, as defined using the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria (2013) - SSc disease duration of =10 and =3 units compared with the most recent assessment performed within the previous 6 months; Involvement of one new body area and an increase in mRSS of >=2 units compared with the most recent assessment performed within the previous 6 months; Involvement of two new body areas within the previous 6 months; Presence of at least one tendon friction rub - Presence of at least one of the following at screening: C reactive protein (CRP)>=0.6 milligrams (mg) per deciliter (dL) (>=6 mg/Liter [L]); erythrocyte sedimentation rate (ESR)>=28 millimeter per hour (mm/hr); Platelet count>=330 x 10^9/L (330,000/microliter) - Uninvolved or mildly thickened skin at one of the following possible injection site locations: Front, middle region of the thigh; Abdomen, except for the 2-inch area directly around the navel; Outer area of the upper arm (if a patient caregiver is giving the injection) - For women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: - Pregnant or lactating, or intending to become pregnant during the study - Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 12 months following randomization - Skin thickening (scleroderma) limited to the face or areas distal to the elbows or knees at screening - Rheumatic autoimmune disease other than SSc, including but not limited to rheumatoid arthritis (RA) (diagnosed using ACR/EULAR criteria), systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjögren's syndrome, and eosinophilic myalgia syndrome, as determined by the investigator - History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies - Evidence of moderately severe concurrent nervous system, renal, endocrine, or gastrointestinal (GI) disease not related to SSc, as determined by the investigator Pulmonary disease with FVC <=55% of predicted (best of three measurements) or diffusion capacity of the lung for carbon monoxide [DLCO] (hemoglobin corrected) <=45% of predicted (best of three measurements) - Class II or higher pulmonary arterial hypertension (PAH), as defined by the World Health Organization - Evidence of other moderately severe pulmonary disease (e.g., asthma, emphysema), as determined by the investigator - Cardiovascular disease with significant arrhythmia, congestive heart failure (New York Heart Association Class II-IV), unstable angina, uncontrolled hypertension, cor pulmonale, or symptomatic pericardial effusion - History of myocardial infarction in the last 6 months prior to screening - Current liver disease, as determined by the investigator - History of diverticulitis or chronic ulcerative lower GI disease, such as Crohn disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations - Known active current or significant history of recurrent bacterial, viral, fungal, mycobacterial, or other infections, including but not limited to atypical mycobacterial disease, hepatitis B or C, herpes zoster, infected digital ulcers, and osteomyelitis - Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening - Significant history of recurrent tuberculosis (TB), active TB requiring treatment within the previous 3 years, or untreated latent TB. Patients should be screened for latent TB, and, if positive, will be eligible for the study after treatment per local standard practices - History of or currently active primary or secondary immunodeficiency - Evidence of malignant disease, or malignancies diagnosed within the previous 5 years (with the exception of local basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured) - Neuropathies or other conditions that might interfere with pain evaluation, as determined by the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of tocilizumab (TCZ) compared with placebo on skin sclerosis, as measured by modified Rodnan Skin Score (mRSS) at Week 48; Secondary Objective: •To evaluate the efficacy of TCZ on pulmonary function, patient-reported outcomes, Physician's Global Assessment and time to treatment failure up to Week 48 •To evaluate the safety of TCZ, focusing on the nature, frequency, and severity of serious and non-serious adverse events, the frequency of SSc-related complications, and effects on vital signs, physical findings, and clinical laboratory results, and by assessing the number of digital ulcers •To assess the long-term safety of TCZ •To characterize the immunogenic potential of TCZ and to assess the potential relationship between development of anti TCZ antibodies and efficacy, safety, or pharmacokinetic (PK) outcome measures •To compare changes in levels of pharmacodynamic biomarkers following treatment with TCZ versus placebo •To characterize the pharmacokinetics of TCZ and evaluate potential relationships between PK parameters for TCZ and efficacy, safety, or immunogenicity outcome measures ;Primary end point(s): Change in mRSS from baseline to Week 48;Timepoint(s) of evaluation of this end point: Baseline and up to Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportions of patients with >= 20%, >= 40%, and >= 60% improvement in mRSS at Week 48 compared with baseline 2. Change in FVC from baseline to Week 48 3. Change in HAQ-DI from baseline to Week 48 4. Change in Patient's Global Assessment from baseline to Week 48 5. Change in Physician's Global Assessment from baseline to Week 48 6. Time to treatment failure, defined as the time from randomization to the time of one of the following events (whichever occurs first) during the 48-week double-blind treatment period: death, decline in percentpredicted FVC > 10% relative to baseline, or > 20% increase in mRSS and an increase in mRSS of >= 5 points occurrence of a predefined SSc-related complication as adjudicated by the Clinical Adjudication Committee 7. Frequency of deaths 8. Nature, frequency, and severity of adverse events 9. Incidence of specific laboratory abnormalities 10. Change from baseline in digital ulcer count 11. Incidence of anti-TCZ antibodies during the study relative to the prevalence of anti TCZ antibodies at baseline 12. Correlation between anti-TCZ antibody status and efficacy, safety, or PK outcome measures 13. Predose ESR and serum IL-6, sIL-6R, and CRP levels at baseline and at subsequent timepoints after initiation of study drug 14. Predose serum TCZ concentration at baseline and at specified timepoints thereafter 15. Correlation between PK parameters for TCZ and efficacy, safety, or immunogenicity outcome measures ; Timepoint(s) of evaluation of this end point: 1. Baseline and Week 48 2-5. Baseline until Week 48 6. Up to Week 48 7-12. Up to 2 years 13. Baseline (BL), Week (WK) 4, WK 8, WK 16, WK 24, WK 36, WK 4 | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Lithuania, Mexico, Netherlands, Poland, Portugal, Romania, South Africa, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed