Study of Daxdilimab (HZN-7734) in Patients With Moderate-to-Severe Primary Discoid Lupus Erythematosus

Discoid Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05591222
• Other study ID #: HZNP-DAX-202
• Secondary ID: 2022-000831-21
• Status: Recruiting
• Phase: Phase 2
• Start date: October 12, 2022
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Approximately 99 participants will be enrolled to receive daxdilimab or placebo administered subcutaneously once every four weeks (Q4W) from Day 1 to Week 44. After week 24 all subjects will be receiving daxbilimab, including those assigned to the placebo arm, Q4W from Week 24 to Week 44. The maximum trial duration per participant is approximately 60 weeks including screening, the 48 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 discoid lupus erythematosus 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:
• In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to Screening, or
• 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, cytomegalovirus (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.

Related Conditions & MeSH terms

• Discoid Lupus Erythematosus
• Lupus Erythematosus, Discoid
• Lupus Erythematosus, Systemic

Intervention

Drug:
• Placebo/Daxdilimab
Placebo/Daxdilimab will be administered subcutaneously as two injections for each dose.
• Daxdilimab
Daxdilimab will be administered subcutaneously as two injections for each dose.
• Daxdilimab
Daxdilimab will be administered subcutaneously as two injections for each dose.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in Cutaneous Lupus Erythematosus Disease and Severity Index-Activity (CLASI-A) score from Baseline to Week 24.		Day 1 to Week 24
Secondary	Proportion of participants who achieve 0 or 1 on the Cutaneous Lupus Activity-Investigator's Global Assessment (CLA-IGA) scale at Week 24 (5-point Likert scale [0-4]).		Day 1 to Week 24
Secondary	Proportion of participants who achieve a = 50% reduction in Cutaneous Lupus Erythematosus Disease and Severity Index-Activity (CLASI-A) score from Baseline (Day 1) at Week 24.		Day 1 to Week 24
Secondary	Mean change in the Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE) from Baseline (Day 1) to Week 24 patients with primary DLE.		Day 1 to Week 24
Secondary	Serum concentration of daxdilimab over time.		Day 1 to Week 48
Secondary	Anti-Drug Antibody (ADA) rate.		Day 1 to Week 56
Secondary	Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent adverse events of special interest (TEAESIs).		Day 1 to Week 56