E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
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E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus Erythematosus |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
● To determine whether treatment with LY3471851 Q2W is superior to placebo in reducing the signs and symptoms of SLE as measured by SLEDAI-4 |
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E.2.2 | Secondary objectives of the trial |
● To determine whether treatment with LY3471851 Q2W is superior to placebo in reducing other measures of signs and symptoms of SLE |
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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 |
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of LY3471851 (NKTR-358) in Adults with Systemic Lupus Erythematosus Approval Date: 27-Mar-2020 Objectives: The data collected via this addendum will be used, in combination with data collected via the main protocol, for exploratory analyses ● to characterize the PK profile of LY3471851 and the dose-response and/or exposure-response as related to PD markers, and ● to compare LY3471851 dose levels with respect to adverse events, including ISRs. During the required screening period for the main study, participants will be given the opportunity to consent to the procedures described in this addendum. Participation in this addendum is optional. |
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E.3 | Principal inclusion criteria |
- Have received a clinical diagnosis of SLE at least 24 weeks before the screening visit (Visit 1). - Have documentation of having met at least 4 of the 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 ACR (Tan et al. 1982; Hochberg 1997) before randomization. - Have a positive ANA (titer ≥1:80) and/or a positive anti-dsDNA and/or positive anti-Sm antibody test at screening (Visit 1) as assessed by the central laboratory - Have a SLEDAI-2K score ≥6 at screening (Visit 1) and clinical SLEDAI-2K score ≥4 at randomization (Visit 2). - Have active arthritis and/or active rash as defined by the SLEDAI-2K at screening and at randomization.
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E.4 | Principal exclusion criteria |
- Are currently receiving oral corticosteroids at doses >20 mg per day of prednisone (or equivalent) or have adjusted the dosage of corticosteroids within 2 weeks before randomization (Visit 2). - Have received topical corticosteroids, other than stable doses of Class VI (mild, such as desonide) or Class VII (least potent, such as hydrocortisone), within 8 weeks before randomization (Visit 2). - Have received parenteral (that is, intravenous or intramuscular) corticosteroids within 12 weeks before randomization (Visit 2) or are expected to require parenteral corticosteroids during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary comparison of interest is the difference in proportion of participants who achieve SLEDAI-4 response at Week 24.
The primary comparison will be assessed using a composite estimand where the intercurrent events of premature discontinuation and use of prohibited medication are part of the response definition.
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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) |
Secondary comparisons of interest are the difference in proportion of participants who at Week 24 achieve: ● BILAG-based Composite Lupus Assessment (BICLA) response ● SRI-4 response ● Lupus Low Disease Activity State (LLDAS)
Secondary objectives will be assessed using a composite estimand (as described above). |
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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 | No |
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 | Yes |
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) | No |
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 | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Argentina |
Australia |
Canada |
Czech Republic |
Germany |
Hungary |
India |
Israel |
Japan |
Korea, Republic of |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 15 |