|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Moderate-to-severe Systemic Lupus Erythematosus (SLE)
|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.
|Diseases [C] - Immune System Diseases [C20]
|E.1.2 Medical condition or disease under investigation
|Systemic lupus erythematosus
|System Organ Class
|10028395 - Musculoskeletal and connective tissue disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To compare efficacy of anifrolumab with placebo on overall disease activity in patients with SLE.
|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) OCS use.
To compare the efficacy of anifrolumab with placebo on the onset of first flare.
|Trial contains a sub-study
|Principal inclusion criteria
|1.Patients who have a diagnosis of paediatric 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 coming from clinical components ("Clinical" SLEDAI-2K") at screening. In addition, the following criteria must be met:
Clinical SLEDAI of at least ≥ 4 points at Day 1 (randomization).
Note: The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures: Includes points from the following clinical components: arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, or vasculitis. Excludes points attributed to a fever, an SLE headache, and organic brain syndrome. Clinical SLEDAI-2K points at screening cannot only be due to alopecia and mucosal ulcers.
3.At Screening, BILAG2004 with at least 1 of the following as confirmed by Disease Activity Central Team Review:
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 antimalarials and/or immunosuppressants and glucocorticoids alone or in combination
All fertile males who are sexually active must use condom from Day 1 until at least 16 weeks after receipt of the final dose of study intervention. It is strongly recommended that the female partner of a male patient also use an effective method of contraception from Table 9 throughout this period.
Male patients must not donate sperm during the course of the study and for 16 weeks after the last dose of the study intervention.
Negative serum β-human chorionic gonadotropin (β-hCG) test at screening (females of childbearing potential only).
Women of childbearing potential must have a negative urine pregnancy test at randomisation (Day 1), prior to administration of study intervention.
Woman of non-childbearing potential must be postmenopausal or have been surgically sterilised (for example: bilateral oophorectomy, or complete hysterectomy), which should be documented in the patient's medical records.
Age-specific requirements may apply for a postmenopausal state. Females of childbearing potential must use 1 highly effective method of contraception plus a male condom, from Screening until 16 weeks after the final dose of study intervention, unless the patient is surgically sterile (eg, bilateral oophorectomy, tubal ligation or complete hysterectomy), has a sterile male/non-fertile male partner, is at least 12 months postmenopausal, or practices sustained abstinence consistent with the patient’s customary lifestyle.
Females who have been or are sexually active with an intact cervix must have ocumentation of a cervical cancer screening (Pap smear or human papilloma virus [HPV] tests as per local guidelines) with a normal test result within 2 years prior to randomisation. Any abnormal cervical cancer screening result documented within 2 years prior to randomisation must be repeated to confirm patient eligibility.
Females aged < 25 years, who have never been sexually active or have well-documented HPV vaccination records may not require a cervical cancer screening test.
|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 eg. prolonged hospitalisation [hospitalisation for observational purposes is not exclusionary] or any prior COVID-19 infection with documented long COVID and/or clinically significant unresolved sequelae
Any mild/asymptomatic COVID-19 infection (lab confirmed or suspected based on clinical symptoms) within the last 6 weeks prior to first dosing
8.Lactating, breastfeeding or pregnant females or females who intend to become pregnant or begin
breastfeeding anytime from initiation of Screening until the end of the 16-week safety follow-up period following last dose of study intervention.
|E.5 End points
|Primary end point(s)
|BICLA a composite binary response defined by meeting all of the following criteria:
-Reduction of all baseline 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 B
-No worsening from baseline in 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 PGA VAS
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|1.Proportion of patients who are BICLA responders at Week 52, and have maintained low (or reduced) OCS use through Week 52
•Maintained low (or reduced) OCS use is defined as follows:
-If baseline OCS ≥ 10mg/day an OCS dose of ≤ 7.5mg/day prednisone or equivalent must be achieved by Week 40 and an OCS dose ≤ 7.5mg/day prednisone or equivalent must be maintained form Week 40 to Week 52
-If baseline OCS < 10mg/day, OCS dose at Week 40 must be less than or equal to OCS dose at baseline, with no increase from Week 40 OCS dose between Week 40 and Week 52.
2.The time from first dose of study intervention during the Double-Blind Study Period to first BICLA response sustained through 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.
|Timepoint(s) of evaluation of this end point
|1. at week 52
2. through week 52
2. through week 52
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
|Other trial design description
|an OLE Period; A Follow-up Period;
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|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.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months