E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-to-severe Systemic Lupus Erythematosus (SLE) |
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E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus Erythematosus is a disease in which the body's own immune system attacks its own cells and tissues, leading to inflammation and damage. |
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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 compare efficacy of anifrolumab with placebo on overall disease activity in patients with SLE. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of anifrolumab with placebo on the onset of a sustained reduction in disease activity.
To compare the efficacy of anifrolumab with placebo on improvement in overall disease activity and low (or reduced) oral corticosteroids (OCS) use.
To compare the efficacy of anifrolumab with placebo on the onset of first flare.
To compare the efficacy of anifrolumab with placebo on early reduction in overall disease activity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients who have a diagnosis of pediatric or adult SLE according to the ACR 1997 revised criteria for ≥ 24 weeks prior to signing the ICF
2.To be eligible a patient must have SLEDAI-2K ≥ 6 points and “Clinical” SLEDAI-2K score ≥4 points at screening
- If a patient’s clinical disease activity is predominantly due to arthritis, the patient must have at least 3 tender and 3 swollen joints
- If a patient’s clinical disease activity is predominantly due to mucocutaneous activity, rash must be present with or without alopecia, mucosal ulcers
3.BILAG2004 with at least 1 of the following:
a.BILAG2004 level A disease in ≥ 1 organ system
b.BILAG2004 level B disease in ≥ 2 organ systems
4.Physician’s Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening
5.Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,
6.Must be on stable background standard therapy with therapy with immunosuppressants and glucocorticoids alone or in combination
7.Contraception Requirements
Male patients:
All males (sterilized or non-sterilized) who are sexually active must use condom (with spermicide where commercially available for contraception) from Day 1 until at least 12 weeks after receipt of the final dose of IP. It is strongly recommended that the female partner of a male patient also use an effective method of contraception from Table 5 (other than a barrier method) throughout this period.
Male patients must not donate sperm during the course of the study and for 12 weeks after the last dose of the IP.
Female patients:
Negative serum β-human chorionic gonadotropin (β-hCG) test at screening (females of childbearing potential only).
Women of child-bearing potential must have a negative urine pregnancy test at randomization (Day 1), prior to administration of IP.
Females of childbearing potential must use 2 effective methods of avoiding pregnancy, only one of which is a barrier method, from Screening until 12 weeks after the final dose of IP, unless the patient is surgically sterile (eg, bilateral oophorectomy or complete hysterectomy), has a sterile male partner, is at least 1 year postmenopausal, or practices sustained abstinence consistent with the patient’s customary lifestyle. Postmenopausal is defined as at least 1 year since last menses and the patient has an elevated follicle-stimulating hormone (FSH) level greater than the central laboratory value of post-menopausal at screening |
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E.4 | Principal exclusion criteria |
1.Active severe or unstable neuropsychiatric SLE
2.Active severe SLE-driven renal disease
3.Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the patient to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at Screening.
4.Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),
5.Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.
6.History of cancer, apart from:
a. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1)
b. Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1)
7.Any history of severe COVID-19 infection or any confirmed or probable COVID-19 infection within 3 months prior to randomization
8.Lactating or pregnant females or females who intend to become pregnant or begin
breastfeeding anytime from initiation of Screening until the end of the 12-week safety follow-up period following last dose of IP |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response, a composite binary response defined by meeting all of the following criteria:
-Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no
BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new
BILAG-2004 A or ≥ 2 new BILAG-2004
-No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of > 0 points in SLEDAI-2K
-No worsening from baseline in patients' lupus disease activity, where worsening is defined by an increase ≥ 0.30 points on a 3 point Physician's Global Assessment (PGA) visual analogue scale (VAS)
-No discontinuation of investigational product (IP)
-No use of restricted medications beyond the protocol allowed threshold before assessment |
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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) |
1.The time from first dose of study treatment to first BICLA response sustained through week 52
2.Proportion of patients who are BICLA responders at Week 52, and have maintained low (or reduced) OCS use Week 52
3.Time to flare through Week 52 where flare is defined as either 1 or more new BILAG-2004 A or 2 or more new BILAG 2004 B items compared to the previous visit.
4.Proportion of patients who are BICLA responders at Week 16 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. through week 52
2. at week 52
3. through week 52
4. at week 16 |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
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
| 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Chile |
Colombia |
Japan |
Mexico |
Peru |
United States |
Poland |
Bulgaria |
Spain |
Germany |
Hungary |
Russian Federation |
Ukraine |
United Kingdom |
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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 is defined as the date of the last scheduled procedure shown in the SoA for the last patient in the study globally. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |