Clinical trial NCT06015737: A 2-stage, Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus
Official title: A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Study to Evaluate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus Who Are Refractory and/or Intolerant to Antimalarial Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cutaneous Lupus Erythematosus
Keywords: Lupus erythematosus
Cutaneous lupus erythematosus
Anifrolumab
Cutaneous Lupus Erythematosus Disease Area Severity Index
Cutaneous lupus activity - Investigator's Global Assessment - Revised
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-08-29
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel group treatment study in two concurrent stages (Stage 1 and Stage 2) and each stage will have two arms.
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the efficacy and safety of subcutaneous (SC) anifrolumab versus placebo in adult participants with cutaneous lupus erythematosus (CLE).

Detailed description: The primary objectives of the study are to evaluate the efficacy of anifrolumab compared with placebo in reducing skin disease in participants with active chronic and/or subacute CLE who are refractory and/or intolerant to antimalarial therapy. The secondary objectives of the study are to evaluate additional efficacy parameters of anifrolumab, safety, tolerability, quality of life, pharmacokinetics, pharmacodynamics, and immunogenicity. Stage 1 and Stage 2 of the study will have broadly identical study designs with the exception of sample size. Both Stages of the study will have a randomized, double-blind, placebo-controlled design, followed by an open-label treatment period.

Eligibility criteria: Key inclusion criteria:

* 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.
  * CLA-IGA-R erythema score of ≥ 3 and CLA-IGA-R-OMC score of ≥ 1 at Screening and confirmed at randomization.
  * Inadequate response or intolerant to antimalarial therapy.
* 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.
* Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Participants should have a coronavirus disease 2019 (COVID-19) negative PCR or antigen test result as per local policies at Screening.

Key exclusion criteria:

* History or evidence of suicidal ideation.
* Severe or life-threatening Systemic lupus erythematosus (SLE).
* Active SLE or Sjögren's Syndrome.
* Any active skin conditions other than CLE that may interfere with the study.
* History of recurrent infection requiring hospitalization and IV antibiotics.
* COVID-19 infection
* Any history of an anaphylactic reaction to human proteins, or monoclonal antibodies.
* 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Stage 1 and Stage 2 (United States [US]): Number of participants with Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 and at least a 2- point reduction relative to baseline
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (European Union [EU]/Rest of the World [ROW]: Number of participants with a 70% reduction relative to baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score
timeFrame: At Week 24
Secondary outcomes:
measure: Stage 1 and Stage 2 (US): Number of participants who achieve a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (US): Number of participants who achieve a CLA-IGA-R OMC score of 0.
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R follicular activity score of 0
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (EU/ROW): Percent change from baseline in total CLASI-A erythema score
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (EU/ROW): Percent change from baseline in total CLASI-A scale/hypertrophy score
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline, or a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline
timeFrame: At Week 12
measure: Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline
timeFrame: At Week 12
measure: Stage 1 and Stage 2 (EU/ROW): Number of participants with CLASI-70 response
timeFrame: At Week 12
measure: Stage 1 and Stage 2 (US/EU/ROW): Change from baseline in Skindex-29+3 domain scores
timeFrame: At Week 24
measure: Stage 1 and Stage 2 (US/EU/ROW): Serum trough (pre-dose) concentrations of anifrolumab
timeFrame: Double-blind: Pre-dose on Day 1 (Week 0), Weeks 1, 4, 12, 24; Open-label: Weeks 40, and 52 or early discontinuation visit [EDV] and follow-up visit (13 Weeks after last dose)
measure: Stage 1 and Stage 2 (US/EU/ROW): Number of participants with positive antidrug antibody
timeFrame: Double-blind: Pre-dose on Day 1 (Week 0), Weeks 4, 12, and 24; Open-label: Pre-dose on Weeks 40, and 52 or EDV and follow-up visit (13 weeks after last dose)
measure: Stage 1 and Stage 2 (US/EU/ROW): Percent change from baseline in suppression of the Interferon 21-gene
timeFrame: Double-blind: Day 1 (Week 0), Week 1, 4, 12, and 24; Open-label; Week 40 and 52 or EDV and follow-up visit (13 weeks after last dose)
measure: Stage 2 (US/EU/ROW): Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score
timeFrame: At Week 24
measure: Stage 2 (US): Number of participants who are CLA-IGA-R erythema responders from Week 24 up to and including Week 52
timeFrame: Up to Week 52
measure: Stage 2 (EU): Number of participants who are CLASI-70 responders up to and including Week 52
timeFrame: Up to Week 52
Other outcomes:
measure: Stage 1 and Stage 2 (US, EU and ROW): Number of participants with adverse events
timeFrame: Screening (up to and including 42 days before Day 1) until Safety Follow-up Period (13 weeks from Week 52/ EDV)
Locations:
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city: Santiago
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city: Baotou
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city: Chengdu
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city: Guangzhou
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city: Hangzhou
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city: Heilongjiang
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city: Kunming
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city: Wuhan
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country: Colombia
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city: Okayama-shi
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city: Ono
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city: Osaka-shi
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city: Sapporo
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city: Suita
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city: Wakayama
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city: Yokohama-shi
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city: Yokohama
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city: Seoul
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city: Guadalajara
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city: Guadalajara
country: Mexico
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country: Mexico
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city: San Luis Potosi
country: Mexico
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city: Veracruz
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city: Zapopan
country: Mexico
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city: Amsterdam
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country: Netherlands
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city: Hamilton
country: New Zealand
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city: Papatoetoe
country: New Zealand
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Lipa
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Gdynia
country: Poland
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city: Katowice
country: Poland
facility: Research Site
city: Kielce
country: Poland
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city: Olsztyn
country: Poland
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city: Ossy
country: Poland
facility: Research Site
city: Poznan
country: Poland
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city: Rzeszów
country: Poland
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
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city: Braga
country: Portugal
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city: Coimbra
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city: Lisboa
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city: Porto
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city: Bucharest
country: Romania
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city: Bucuresti
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city: Craiova
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city: Iasi
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city: Targu Mures
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city: Belgrade
country: Serbia
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city: Belgrade
country: Serbia
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city: Kragujevac
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city: Košice
country: Slovakia
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city: Piestany
country: Slovakia
facility: Research Site
city: Piestany
country: Slovakia
facility: Research Site
city: Svidnik
country: Slovakia
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city: Cape Town
country: South Africa
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city: Johannesburg
country: South Africa
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city: Stellenbosch
country: South Africa
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Castellon de la Plana
country: Spain
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city: Granada
country: Spain
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city: L'Hospitalet de Llobregat
country: Spain
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city: La Coruña
country: Spain
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city: Las Palmas de Gran Canaria
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Majadahonda
country: Spain
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city: Salamanca
country: Spain
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city: Sevilla
country: Spain
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city: Valencia
country: Spain
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city: València
country: Spain
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city: Vigo
country: Spain
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city: Kaohsiung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
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city: Bangkok
country: Thailand
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city: Bangkok
country: Thailand
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city: Hat Yai
country: Thailand
facility: Research Site
city: Khlong Luang
country: Thailand
facility: Research Site
city: Khon-Kaen
country: Thailand
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
References: