E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
This disease is characterized by scaring of the skin and internal organs. This leads to tightening and thickening of the skin and can lead to problems with other internal organ functions. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To assess the efficacy of treatment with TCZ 162 mg SC versus placebo SC given every week to patients with SSc, at Week 24 using the mRSS
•To assess the safety of treatment with TCZ 162 mg SC versus placebo SC given every week
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E.2.2 | Secondary objectives of the trial |
•To assess the efficacy of TCZ 162 mg SC versus placebo on improvement of physical function (as measured by the Scleroma Health Assessment Questionaire-Disability Index [SHAQ-DI])
•To assess the efficacy of TCZ 162 mg SC versus placebo on patient’s global assessment
•To assess the efficacy of TCZ 162 mg SC versus placebo on improvement of the clinician's global assessment
•To assess the efficacy of TCZ 162 mg SC versus placebo on fatigue (as measured by Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue] score)
•To assess the efficacy of TCZ 162 mg SC versus placebo as measured on Pruritus 5-D Itch Scale (5-D Itch Scale)
•To assess the efficacy of TCZ 162 mg SC versus placebo at Week 48 on skin thickness using the mRSS
•To assess the proportion of patients with maintenance of mRSS response from Week 24 to Week 48
•To characterize the PK and PD profile of TCZ 162 mg SC
•To assess the immunogenicity of TCZ 162 mg SC |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To determine the pharmacokinetics of TCZ in SSc patients, additional PK samples following the first SC dose at baseline and the Week 16 dose will be drawn from approximately 24 patients at selected sites. |
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E.3 | Principal inclusion criteria |
•Ability and willingness to give written informed consent and comply with the requirements of the study protocol
•Diagnosis of SSc, as defined using ACR criteria
•Disease duration of ≤ 60 months (defined as time from the first non-Raynaud phenomenon manifestation)
•Age ≥ 18 years
•≥ 15 and ≤ 40 mRSS units at the screening visit
•Uninvolved skin at injection sites
•Active disease
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E.4 | Principal exclusion criteria |
•Rheumatic autoimmune disease other than SSc, including but not limited to, RA, systemic lupus erythematosis, mixed connective tissue disorder, polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjögren syndrome and eosinophilic myalgia syndrome
•Skin thickening (scleroderma) limited to areas distal to the elbows or knees at screening
•History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
•Evidence of moderately severe concomitant nervous system, renal, endocrine or GI disease, as determined by the Principal Investigator
•Pulmonary disease with FVC ≤ 50% of predicted or a DLCO (hemoglobin corrected) ≤ 40% of predicted |
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E.5 End points |
E.5.1 | Primary end point(s) |
modified Rodnan Skin Score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Change in HAQ-DI score from baseline at week 24 and week 48
•Change in patient’s global assessment from baseline at week 24 and week 48
•Change in clinician’s global assessment from baseline at week 24 and week 48
•Change in FACIT-F score from baseline at week 24 and week 48
•Change in Pruritus 5-D Itch scale from baseline at week 24 and week 48
•Change in mRSS from baseline at week 48
•Proportion of patients with mRSS at week 48 ≥ mRSS at week 24
•Change in VAS scores from baseline (intestinal, breathing, Raynaud’s, finger ulcers, overall disease VAS scores from SHAQ-DI) at Weeks 24 and 48
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity assessment |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
48-week blinded period followed by a 48-week open-label period |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study will occur when the last participating patient completes the last scheduled visit or when the Sponsor decides to discontinue the study or development program. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |