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 |
Dermatomyositis is a rare disease that causes muscle inflammation and skin problems (rash and swelling). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012503 |
E.1.2 | Term | Dermatomyositis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous 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 |
PART A To determine the effect of ravulizumab compared with placebo in the treatment of DM based on improvement in Total Improvement Score (TIS) as per 2016 ACR/EULAR Myositis Response Criteria for adult DM (also known as IMACS).
PART B To determine the effect of ravulizumab compared with placebo in the treatment of DM based on improvement in Total Improvement Score (TIS) as per 2016 ACR/EULAR Myositis Response Criteria for adult DM (also known as IMACS) |
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E.2.2 | Secondary objectives of the trial |
PART A To assess the efficacy of ravulizumab compared with placebo in the treatment of DM based on improvement in efficacy endpoints. To characterize the PK/PD and immunogenicity of ravulizumab in adult participants with DM. To characterize the overall safety of ravulizumab in participants with DM.
PART B To assess the efficacy of ravulizumab compared with placebo in the treatment of DM based on improvement in components of IMACS and other myositis activity measures To assess the efficacy of ravulizumab compared with placebo in the treatment of DM based on other efficacy endpoints To characterize the PK/PD and immunogenicity of ravulizumab in adult participants with DM To characterize the overall safety of ravulizumab in participants with DM |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply: 1. 18 years of age or older at the time of signing the informed consent. 2.Body weight ≥ 30 kg at the time of Screening. 3. Male or female. 4. Diagnosis: Meet American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for definite or probable DM (Lundberg, 2017). 5. Participants who have an inadequate response (ie, continued impairment by medical doctor report) or are intolerant to 2 or more DM treatments, including systemic corticosteroids or ISTs (eg, azathioprine, methotrexate, rituximab, IVIg), either in combination or as monotherapy. 6. Vaccinated against Neisseria meningitidis within 3 years prior to, or at the time of, initiating ravulizumab. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics until 2 weeks after the vaccination. 7. Female participants of childbearing potential and male participants must follow specified contraception guidance as described in the protocol. |
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E.4 | Principal exclusion criteria |
1. Cancer-associated myositis, defined as the diagnosis of myositis within 3 years of the diagnosis of cancer (except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 3 months before Screening). 2. Evidence of active malignant disease or malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors). 3. Participants with other forms of myositis 4. Participants with significant muscle damage (eg, severe muscle atrophy, end stage muscle disease) as per investigator opinion. 5. History of Neisseria meningitidis infection. 6. Human immunodeficiency virus (HIV) infection (evidenced by HIV Type 1 or Type 2 antibody titer). 7. Active systemic bacterial, viral, or fungal infection within 14 days prior to ravulizumab administration. 8. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on Day 1. 9. History of hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab. 10. Pregnant, breastfeeding, or intending to conceive during the course of the study. 11. Inability or unwillingness to adhere to the protocol requirements
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E.5 End points |
E.5.1 | Primary end point(s) |
PART A Proportion of participants with a ≥ 20-point improvement response on TIS (TIS20) at Week 26 of the Randomized-Controlled Period
PART B Proportion of participants with a ≥ 20-point improvement response on TIS (TIS20) at Week 50 of the Randomized-Controlled Period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A: Week 26 Part B: Week 50
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E.5.2 | Secondary end point(s) |
PART A • Mean TIS at Week 26 • Mean change from baseline in CDASI Activity Score at Week 26 • Change from baseline of IMACS core set measures at Week 26 • Time to first CDASI Activity Score improvement • Change in Investigator Global Assessment (IGA) at Week 26
PART B • Mean TIS at Week 50 • Mean change from baseline in MMT-8 at Week 50 • Mean change from baseline in extra-muscular disease activity based on MDAAT at Week 50 • Mean change from baseline in CDASI Activity Score at Week 50 • Mean change from baseline in individual 6 CSM used for TIS calculation • Time to first CDASI Activity Score improvement |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.7.1.3.1 | Other trial type description | |
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 | No |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Japan |
Korea, Republic of |
United States |
France |
Germany |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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A participant is considered to have completed the study if the participant has completed all periods (Randomized-Controlled Period and OLE Period) of the study including the last scheduled procedure shown in the SoA (Section 1.3) of the protcol. The end of the study is defined as the date the last participant completes the last visit shown in the SoA.
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 6 |