Subcutaneous Anifrolumab in Adult Patients with Systemic Lupus Erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

22 Oct 2021 → ongoing

Decision date (initial)

2024-05-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-513031-24-00

EudraCT number

2020-004529-22

ClinicalTrials.gov

NCT04877691

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacodynamic, Therapy, Safety, Others, Pharmacokinetic

To compare efficacy of anifrolumab with placebo on overall disease activity in patients with SLE.

Secondary objectives 3

1. To compare the efficacy of anifrolumab with placebo on improvement in overall disease activity and low (or reduced) OCS use.
2. To compare the efficacy of anifrolumab with placebo on the onset of a sustained reduction in disease activity
3. To compare the efficacy of anifrolumab with placebo on the onset of first flare

Conditions and MedDRA coding

Moderate-to-severe Systemic Lupus Erythematosus (SLE)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

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 a total SLEDAI-2K ≥ 6 points, with ≥ 4 points coming from clinical components (“Clinical” SLEDAI-2K”) at Screening (for additional details see a,b,c,d)
3. At Screening, BILAG-2004 with at least 1 of the following as confirmed by Disease Activity Central Review Team: (a) BILAG-2004 level A disease in ≥ 1 organ system (b) BILAG-2004 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/or anti-Smith positive at Screening.
6. Must be on stable background standard therapy with antimalarials and/or immunosuppressant(s) and glucocorticoids alone or in combination
7. 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.
8. Male patients must not donate sperm during the course of the study and for 16 Weeks after the last dose of the study intervention
9. Negative serum β-human chorionic gonadotropin (β-hCG) test at Screening (females of childbearing potential only).
10. Women of childbearing potential must have a negative urine pregnancy test at randomisation (Day 1), prior to administration of study intervention
11. Women 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
12. Age-specific requirements may apply for a postmenopausal state
13. Females of childbearing potential must use 1 highly effective methods 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/non-fertile male partner, is at least 12 months postmenopausal, or practices sustained abstinence consistent with the patient’s lifestyle
14. Females who have been or are sexually active with an intact cervix must have documentation 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
15. 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.

Exclusion criteria 8

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) or 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 16 Weeks following last dose of study intervention

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. BICLA a composite binary response defined by meeting all criteria as per protocol page 25 and 52

Secondary endpoints 3

1. Proportion of patients who are BICLA responders at Week 52 and have maintained low (or reduced) OSC use through Week 52 maintained low (or reduced) OSC use is defined as per protocol pages 26 and 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Third parties 1

Locations

5 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 197 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications