Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN)

Lupus Nephritis Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy and Safety of Daxdilimab in Adult Participants With Active Proliferative Lupus Nephritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05540665
• Other study ID #: HZNP-DAX-203
• Secondary ID: 2022-001377-31
• Status: Terminated
• Phase: Phase 2
• Start date: April 26, 2023
• Est. completion date: January 4, 2024

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of daxdilimab in patients with active, proliferative lupus nephritis (LN).

Description:

Approximately 210 participants will be randomized to receive daxdilimab or placebo administered subcutaneously through Week 52 in addition to their standard of care background therapy (mycophenolate mofetil (MMF) and corticosteroids). At Week 64, all participants will be assigned to a quarterly dosing maintenance regimen of either daxdilimab or placebo based upon pre-defined renal response observed by Week 52. The maximum trial duration per participant is approximately 116 weeks including a 4-week screening period, the 104 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: Terminated
• Enrollment: 19
• Est. completion date: January 4, 2024
• Est. primary completion date: January 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Willing and able to understand and provide written informed consent

• Adult men or women 18 to 80 years of age

• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial

• Fulfill the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus (SLE)

• Have at least one of the following at Screening per central lab:

• Antinuclear antibodies (ANA) = 1:80

• Anti-dsDNA antibodies elevated to above normal range as established by the central laboratory (ie, positive results)

• Anti-Smith antibodies elevated to above normal (ie, positive results).

• Diagnosis of proliferative LN based on a renal biopsy obtained within 6 months prior to signing the informed consent form (ICF) or during the Screening Period:

• Class III (± class V) or class IV (± class V) LN according to the World Health Organization (WHO) or 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification (based on local evaluation of renal biopsy).

• Urine protein to creatinine ratio =113.17 mg/mmol, obtained via a 24-hour urine collection at Screening.

• Estimated glomerular filtration rate =35 mL/min/1.73 m2

• Negative serum beta-human chorionic gonadotropin test at Screening (females of childbearing potential only).

Key Exclusion Criteria:

• History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the investigational product or to a previous monoclonal antibody or human immunoglobulin therapy.

• Known intolerance to =1.0 gm/day of MMF or equivalent dose of mycophenolic acid (MPA).

• A diagnosis of pure Class V membranous LN based on a renal biopsy obtained within 6 months prior to signing ICF or during the Screening Period.

• History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 12-month period after enrollment.

• History of, or current renal diseases (other than LN) that in the opinion of the Investigator could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy).

• Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection per central laboratory, splenectomy, or any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection.

• Hepatitis B, Hepatitis C, active tuberculosis (TB), any severe herpes infection, clinically active infection, or opportunistic infection.

• Clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization.

• History of cancer within the past 5 years, except in situ carcinoma of the cervix, cutaneous basal cell or squamous cell carcinoma with curative therapy.

• Receipt of a live vaccine within 4 weeks prior to Day 1.

• The use of immunosuppressants, biologics, and DMARDS within the protocol defined washout periods.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Daxdilimab
Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734
• Daxdilimab
Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734
• Placebo (Normal Saline)
Placebo will be administered subcutaneously as two injections for each dose.

Locations

Country	Name	City	State
Argentina	DOM Centro de Reumatologia	Buenos Aires
Argentina	Swiss Medical Center Barrio Parque	Ciudad Autónoma Buenos Aires
Argentina	Aprillus Asistencia e Investigacion de Arcis Salud SRL	Ciudad Autónoma de Buenos Aires
Argentina	Consultorios Médicos Dr. Doreski	Ciudad Autónoma de Buenos Aires
Argentina	Framingham Centro Médico	La Plata	Buenos Aires
Argentina	Instituto Médico de la Fundación Estudios Clínicos	Rosario	Santa Fe
Argentina	Centro de Investigaciones Médicas Tucumán	San Miguel de Tucuman
Argentina	Clinica Mayo de U.M.C.B. S.R.L	San Miguel De Tucumán
Brazil	Santa Casa de Misericórdia de Belo Horizonte - PPDS	Belo Horizonte	Minas Gerais
Brazil	Oncovida- Centro de Onco-Hematologia de Mato Grosso	Cuiabá
Brazil	Centro Mineiro de Pesquisa	Juiz De Fora	Minas Gerais
Brazil	Irmandade Da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	LMK Servicos Medicos SS	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP - PPDS	Ribeirão Preto
Brazil	Clinica Senhor Do Bonfim CSB	Salvador	Bahia
Brazil	SER - Serviços Especializados em Reumatologia da Bahia S/S - ME	Salvador	Bahia
Brazil	Praxis Pesquisa Medica	Santo André
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Praxis Pesquisa Medica	São Paulo
Croatia	Clinical Hospital Centre Osijek	Osijek
Israel	Lady Davis Carmel Medical Center	Haifa	HaMerkaz
Israel	Meir Medical Center	Kfar Sava	HaMerkaz
Israel	Sheba Medical Center - PPDS	Ramat Gan	Tel-Aviv
Malaysia	Hospital Serdang	Kajang
Malaysia	Hospital Putrajaya	Putrajaya
Malaysia	University Malaya Medical Centre	Wilayah Persekutuan - Kuala Lumpur	Kuala Lumpur
Philippines	St. Paul's Hospital	Iloilo City	Iloilo
Philippines	Mary Mediatrix Medical Center	Lipa City	Batangas
Philippines	GreenCity Medical Center	San Fernando City	Pampanga
Poland	SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi	Lódz	Lódzkie
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Dr hab. Med. Eleonory Reicher	Warszawa
Poland	Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy	Warszawa
Serbia	Institute of Rheumatology Belgrade - PPDS	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	University Clinical Center of Serbia - PPDS	Belgrade	Beograd
Serbia	General Hospital Krusevac	Krusevac
Serbia	University Clinical Center Nis	Niš
Serbia	Clinical Centre of Vojvodina	Novi Sad
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital de Manises	Valencia
Taiwan	China Medical University Hospital	Taichung
Thailand	Phramongkutklao Hospital	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Rajavithi Hospital	Din Daeng	Krung Thep Maha Nakhon-Bangkok
Thailand	Ramathibodi Hospital Mahidol University	Din Daeng	Krung Thep Maha Nakhon-Bangkok
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	DaVita Clinical Research - El Paso	El Paso	Texas
United States	Care and Cure Clinic	Houston	Texas
United States	California Kidney Specialists	San Dimas	California
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Croatia,  Israel,  Malaysia,  Philippines,  Poland,  Serbia,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving complete renal response (CRR) at Week 48 and sustained through Week 52.		Week 48 to Week 52
Secondary	Proportion of participants achieving overall renal response (ORR) at Week 48 and sustained through Week 52.		Week 48 to Week 52
Secondary	Change from baseline in estimated glomerular filtration rate (eGFR) at Week 52.		Day 1 to Week 52
Secondary	Proportion of participants able to taper oral corticosteroids (OCS) to target by Week 24 and maintain target dose through Week 52.		Week 24 to Week 52
Secondary	Anti-Drug Antibody (ADA) rate.		Day 1 to Week 116
Secondary	Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent adverse events of special interest (AESIs).		Day 1 to Week 116