A Phase III study to investigate the efficacy and safety of anifrolumab in adults with chronic and/or subacute cutaneous 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] - Skin and Connective Tissue Diseases [C17]

Trial duration

25 Sep 2024 → ongoing

Decision date (initial)

2024-09-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca UK

External identifiers

EU CT number

2023-503692-24-00

ClinicalTrials.gov

NCT06015737

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic, Others

To demonstrate the superiority of anifrolumab to placebo on skin manifestations in participants with CLE at Week 24.

Secondary objectives 8

1. To demonstrate the superiority of anifrolumab to placebo on skin manifestations in participants with CLE at Week 24.
2. To demonstrate the superiority of anifrolumab to placebo on the early clinical response of skin manifestations in participants with CLE at Week 12.
3. To assess the efficacy of anifrolumab compared with placebo on skin-related, health-related quality of life in participants with CLE at Week 24.
4. To assess the efficacy of anifrolumab compared with placebo on the onset of reduction in skin manifestations in participants with CLE.
5. To assess the efficacy of anifrolumab compared to placebo on skin manifestations in participants with CLE at Week 24.
6. To describe sustained response in disease activity through Week 52.
7. To evaluate the PK, PD, and immunogenicity of subcutaneously administered anifrolumab in participants with CLE.
8. To evaluate the safety and tolerability of anifrolumab compared with placebo in participants with CLE.

Conditions and MedDRA coding

Cutaneous Lupus Erythematosus

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and/or female participant must be 18 to 70 years of age inclusive, at the time of signing the ICF.
2. Participants must have a confirmed diagnosis of CLE. Diagnosis must be clinically and histologically confirmed with the following: • CLASI-A total score ≥ 10 points at Screening and confirmed at randomization. • Inadequate response or intolerant to antimalarial therapy. - At least one antimalarial agent used for at least 12 weeks (not continuous is acceptable) prior to Screening. Participants must be on a stable dose of antimalarial agent for at least 2 weeks prior to ICF signature. OR - Previously documented discontinuation of antimalarial agents due to poor tolerability and/or side effects. In case an antimalarial treatment had not been initiated due to medical reasons (in particular the presence of medical contraindications), then at least one of the following medications for CLE must have been tried any time before Screening: • Topical calcineurin inhibitors, administered for ≥ 3 months. • Systemic glucocorticoids taken for ≥ 6 weeks. • A conventional immunosuppressant, including, azathioprine, mycophenolate mofetil (or mycophenolic acid), dapsone, or methotrexate administered for ≥ 3 months.
3. Participants should have no medical history or signs or symptoms of active or prior tuberculosis infection (TB) and the same should reflect in chest radiograph or a chest CT scan result. • No history of latent TB prior to initial Screening Visit. • The participant must undergo an IFN-γ release assay IGRA (e.g., QFT-G test) test for TB.
4. Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
5. Females who have been or are sexually active with an intact cervix must have documentation of a cervical cancer screening (Pap smear or HPV tests as per local guidelines) with a normal test result within 2 years prior to randomization.

Exclusion criteria 17

1. History or evidence of suicidal ideation.
2. Severe or life-threatening SLE.
3. Active SLE or Sjögren’s Syndrome.
4. Any active skin conditions other than CLE that may interfere with the study.
5. History of, or current diagnosis of, catastrophic APS within 1 year prior to signing the ICF.
6. History of recurrent infection requiring hospitalization and IV antibiotics.
7. Known history of primary immunodeficiency, splenectomy, or any underlying condition that makes the participant prone to infection, or a positive result for HIV infection at Screening.
8. Confirmed positive test for hepatitis B serology.
9. Presence of active hepatitis C infection.
10. Any severe case of herpes zoster infection prior to randomization.
11. Any clinical cytomegalovirus (CMV) or Epstein-Barr virus infection that has not been completely resolved.
12. Clinically significant chronic infection within 8 weeks prior to signing the ICF or any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF.
13. COVID-19 infection: • History of severe COVID-19 infection and/or clinically significant unresolved complications due to COVID-19 infection. • Any COVID 19 infection within 2 weeks prior to Day 1.
14. Participants who do not meet the study restrictions for prior receipt of anifrolumab, using all biologics, directly acting cytotoxic B cell-depleting therapies (eg, rituximab), and any investigational product.
15. A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy.
16. Any history of an anaphylactic reaction to human proteins, or monoclonal antibodies.
17. At screening, if participants do not meet the eligibility criteria assessed based on laboratory test results e.g. tests for total bilirubin, serum creatinine etc.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of participants with CLASI-70 response at Week 24.

Secondary endpoints 10

1. Total CLASI A score, change from baseline at Week 24.
2. - Number of participants with CLASI-70 response at Week 12. - Participants with ≥ 7 point reduction from baseline in CLASI A total score (yes/no) at Week 12. - Number of participants with CLASI 50 response at Week 12.
3. Change from baseline at Week 24 in Skindex-29+3 domain scores.
4. - Time from IP start date to CLASI 70 response; - Time from IP start date to CLASI 50 response.
5. Number of participants with CLASI 50 response at Week 24.
6. Number of participants who are primary endpoint responders (CLASI-70 response at Week 24) and sustain CLASI-70 response up to and including Week 52.
7. - Pharmacokinetic (PK) assessment (Ctrough) for subcutaneously administered anifrolumab in participants with CLE will be performed.
8. - Pharmacodynamic (PD) assessment for subcutaneously administered anifrolumab in participants with CLE will be performed.
9. - The immunogenicity of subcutaneously administered anifrolumab in participants with CLE will be evaluated.
10. Number of participants with adverse events.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Centre

Third parties 2

Locations

13 EU/EEA countries · 84 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 188 files

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

Application history

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