Clinical trial NCT05591222: Study of Daxdilimab (HZN-7734) in Participants With Moderate-to-Severe Primary Discoid Lupus Erythematosus
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Investigate the Efficacy and Safety of Daxdilimab Subcutaneous Injection in Reducing Disease Activity in Adult Participants With Moderate-to-Severe Primary Discoid Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Discoid Lupus Erythematosus
Keywords: Discoid Lupus Erythematosus
Immune System Diseases
Lupus Erythematosus, Cutaneous
Skin Diseases
Connective Tissue Diseases
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-10-24
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 2, double-blind, randomized, placebo-controlled parallel-group study to evaluate the efficacy and safety of daxdilimab in participants with moderate-to-severe active primary Discoid Lupus Erythematosus (DLE) refractory to standard of care.

Detailed description: Approximately 72 participants will be enrolled to receive daxdilimab or placebo administered subcutaneously once every four weeks (Q4W) from Day 1 to Week 20. The maximum trial duration per participant is approximately 36 weeks including screening, the 24 weeks for the treatment period where participants will receive daxdilimab or placebo, and approximately 8 weeks for the follow-up period. Safety evaluations will be performed regularly throughout the course of the study.

Acquired from Horizon in 2024.

Eligibility criteria: Key Inclusion Criteria:

* Willing and able to understand and provide written informed consent.
* Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
* A diagnosis of DLE for ≥ 6 months prior to screening supported by a history of:

  1. A biopsy or
  2. a clinical feature score of ≥ 7 on the DLE Classification Criteria (DLECC) scale.
* Currently active discoid lupus with all the following:

  1. Digital photography adjudicated with central reading to confirm a currently active discoid disease lesion.
  2. CLASI-A score ≥ 8 related to discoid lesions at Baseline.
* Treatment refractory DLE defined as active disease despite current or historical treatment with a systemic treatment.
* Females are eligible to participate if they are not pregnant or breastfeeding, and meet the contraceptive/barrier requirement(s).
* Males are eligible to participate if they agree to the contraceptive/barrier requirement(s).
* Vaccination status should be up to date per local standards.

Key Exclusion Criteria:

* Participation in another clinical study with an investigational drug within 4 weeks prior to Randomization or within 5 published half-lives, whichever is longer.
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product (IP) or interpretation of participant safety or trial results.
* Weight \> 160 kg (352 pounds) at Screening.
* History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a previous monoclonal antibody (mAb) or human immunoglobin (Ig) therapy.
* Breastfeeding or pregnant women or women who intend to become pregnant anytime from signing the informed consent form (ICF) through 6 months after receiving the last dose of IP.
* Splenectomy.
* Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to screening through randomization.
* History of clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization; arrhythmia requiring active therapy, except for clinically insignificant extra systoles, or minor conduction abnormalities.
* History of cancer within the past 5 years, except as follows:

  * Cutaneous basal cell or squamous cell carcinoma treated with curative therapy.
* Any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection.
* Known history of a primary immunodeficiency or an underlying condition, such as known human immunodeficiency virus (HIV) infection, or a positive result for HIV infection per central laboratory.
* Participants with positive hepatitis B serologic test results.
* All participants will undergo testing for hepatitis C antibody (HCVAb) during Screening.
* Participants who are HCVAb positive will be reflex tested for hepatitis C virus (HCV) RNA and if HCV RNA is positive, the participant is not eligible for the study.
* Active tuberculosis (TB), or a positive interferon-gamma release assay (IGRA) test at screening, unless documented history of appropriate treatment for active or latent TB.

Participants with an indeterminate IGRA test result can repeat the test, but if the repeat test is also indeterminate, they will be excluded.

* Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus (CMV)) at any time prior to Randomization, including, but not limited to, disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the last 2 years), or ophthalmic herpes.
* Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to Randomization.
* Opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within 2 years prior to Randomization.
* Any acute illness or evidence of clinically significant active infection on Day 1.
* Participants who have COVID-19 or other significant infection, or in the judgment of the Investigator, may be at a high risk of COVID-19 or its complications should not be randomized.
* Systemic lupus erythematosus defined by fulfilling 2020 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for systemic lupus erythematosus (SLE).
* Current diagnosis of a systemic connective tissue disease.
* Current inflammatory skin disease other than DLE, that, in the opinion of the Investigator, could interfere with the inflammatory skin assessments and confound the disease activity assessments.
* Exposure to an experimental drug either 30 days, 5 half-lives of the agent, or twice the duration of the biological effect of the agent, whichever is longer, prior to Randomization and through the final trial visit.
* Receipt of a live-attenuated vaccine within 4 weeks prior to Randomization.

Primary outcomes:
measure: Mean Change in Cutaneous Lupus Erythematosus Disease and Severity Index-Activity (CLASI-A) Score from Baseline to Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Percentage of Participants who Achieve 0 or 1 on the Cutaneous Lupus Activity-investigator's Global Assessment (CLA-IGA) scale at Week 24
timeFrame: Week 24
measure: Percentage of Participants who Achieve a ≥ 50% Reduction in CLASI-A Score from Baseline at Week 24
timeFrame: Baseline to Week 24
measure: Mean Change in the Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE) from Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Serum Concentration of Daxdilimab Over Time
timeFrame: Day 1 to Week 24
measure: Percentage of Participants who Develop Anti-Drug Antibodies (ADA)
timeFrame: Day 1 to Week 32
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 to SFU2 (Week 32)
Other outcomes:
Locations:
city: North Little Rock
country: United States
facility: Arkansas Research Trials
state: Arkansas
city: Beverly Hills
country: United States
facility: Wallace Medical Group
state: California
city: Fremont
country: United States
facility: The Center for Dermatology Clinical Research
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Miami
country: United States
facility: Miami Dermatology & Laser Research
state: Florida
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center, PC
state: Michigan
city: Waterford
country: United States
facility: Michigan Dermatology Institute
state: Michigan
city: New Brighton
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Forest Hills
country: United States
facility: Forest Hills Dermatology
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Fairborn
country: United States
facility: Wright State Physicians
state: Ohio
city: Philadelphia
country: United States
facility: Paddington Testing Company, Inc.
state: Pennsylvania
city: Philadelphia
country: United States
facility: Autoimmune Skin Diseases Unit, Dept. of Dermatology
state: Pennsylvania
city: Houston
country: United States
facility: Center for Clinical Studies (Cypress)
state: Texas
city: Ciudad de Mendoza
country: Argentina
facility: Fundacion Scherbovsky
state: Mendoza
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: CIPREC
city: Fortaleza
country: Brazil
facility: HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
state: Ceará
city: Água Verde
country: Brazil
facility: Hospital Universitário Evangélico Mackenzie
state: Paraná
city: Sao Jose Rio
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto, CIP - Centro Integrado de Pesquisa
state: Preto Sao Paulo
city: Niteroi
country: Brazil
facility: Complexo Hospitalar de Niterói
state: Rio Do Janeiro
city: Rio de Janeiro
country: Brazil
facility: Instituto Brasil de Pesquisa Clínica-IBPCLIN S/A
state: Rio Do Janeiro
city: Caxias do Sul
country: Brazil
facility: Fundação Universidade de Caxias do Sul - Instituto de Pesquisas em Saúde da Universidade de Caxias do Sul
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: LMK Serviços Médicos S/S
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas
state: Sao Paulo
city: Santo André
country: Brazil
facility: Hospital Christovão da Gama - Centro de Estudos
state: Sao Paulo
city: São Bernardo Do Campo
country: Brazil
facility: Centro Multidisciplinar de Estudos Clinicos
state: Sao Paulo
city: Tatuí
country: Brazil
facility: IMC - Instituto de Moléstias Cardiovasculares Tatuí
state: Sao Paulo
city: São Paulo
country: Brazil
facility: IPITEC Instituto de Pesquisa Inovação Tecnológica
city: Haskovo
country: Bulgaria
facility: DCC 'Sveti Georgi' EOOD
city: Sofia
country: Bulgaria
facility: Ambulatory for specialized medical care - individual practice for specialized medical care - skin and venereal diseases
city: Sofia
country: Bulgaria
facility: DCC "Alexandrovska" EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Eurohealth EOOD
city: Edmonton
country: Canada
facility: Alberta DermaSurgery Centre
state: Alberta
city: Fredericton
country: Canada
facility: Brunswick Dermatology Center
state: New Brunswick
city: London
country: Canada
facility: DermEffects
state: Ontario
city: Toronto
country: Canada
facility: North York Research, Inc
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Praha 1
country: Czechia
facility: Sanatorium Profesora Arenbergera
city: Copenhagen NV
country: Denmark
facility: Bispebjerg Hospital, Dermato-Venerologisk Afdeling Og Videncenter for Sårheling, D/S.
city: Odense C
country: Denmark
facility: OUH
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital
city: Nice Alpes
country: France
facility: Service de dermatologie, hôpital Archet 2, CHU NICE
state: Maritimes
city: Lyon
country: France
facility: Hopital Edouard Herriot - CHU Lyon
city: Poitiers Cedex
country: France
facility: CHU Poitiers - Hôpital la Milétrie
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden Wuerttemberg
city: Falkensee
country: Germany
facility: BAG Dr. Freitag und Knöll
state: Brandenburg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg AöR
state: Niedersachsen
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
state: Rheinland Pfalz
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie
state: Sachsen
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos"
city: Athens
country: Greece
facility: 401 General Military Hospital of Athens
city: Athens
country: Greece
facility: University General Hospital "Attikon"
city: Athens
country: Greece
facility: Andreas Syggros Hospital
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: General Hospital Papageorgiou
city: Krakow
country: Poland
facility: Specjalistyczny Gabinet Dermatologiczny Aplikacyjno-Badawczy Marek Brzewski, Pawel Brzewski Spolka Cywilna
city: Malbork
country: Poland
facility: Centrum Badawcze Panaceum Agnieszka Brzezicka Magdalena Lenkiewicz Sp. z o.o.
city: Rzeszów
country: Poland
facility: Kliniczny Szpital Wojewodzki nr 1 im.F.Chopina
city: Szczecin
country: Poland
facility: LASER CLINIC S.C. Dr Tomasz Kochanowski Dr Andrzej Krolicki
city: Warszawa
country: Poland
facility: Clinical Research Group Sp. z o.o.
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: