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

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

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).

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Daxdilimab; Drug: Placebo (Normal Saline)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1111AAH
    • DOM Centro de Reumatología
  • Ciudad Autónoma Buenos Aires, Argentina, 1426
    • Swiss Medical Center Barrio Parque
  • Ciudad Autónoma de Buenos Aires, Argentina, C1406AGA
    • Aprillus Asistencia e Investigacion de Arcis Salud SRL
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
    • Consultorios Médicos Dr. Doreski
  • San Miguel De Tucumán, Argentina, T4000IHE
    • Clínica Mayo de U.M.C.B. S.R.L
  • San Miguel de Tucuman, Argentina, T4000AXL
    • Centro de Investigaciones Médicas Tucuman
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1900
      • Framingham Centro Medico
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2013DTC
      • Instituto Medico de la Fundacion Estudios Clinicos
• Brazil
  • Cuiabá, Brazil, 78043-142
    • Oncovida- Centro de Onco-Hematologia de Mato Grosso
  • Ribeirão Preto, Brazil, 14051-140
    • Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP - PPDS
  • Santo André, Brazil, 09090-790
    • Praxis Pesquisa Médica
  • São Paulo, Brazil, 05403-000
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo
  • São Paulo, Brazil
    • Praxis Pesquisa Médica
  • Bahia
    • Salvador, Bahia, Brazil, 40150-150
      • SER - Serviços Especializados em Reumatologia da Bahia S/S - ME
    • Salvador, Bahia, Brazil, 40415-065
      • Clinica Senhor Do Bonfim CSB
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte - PPDS
    • Juiz De Fora, Minas Gerais, Brazil, 36010-570
      • Centro Mineiro de Pesquisa
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-074
      • Irmandade da Santa Casa de Misericordia de Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90480-000
      • LMK Servicos Medicos SS
• Croatia
  • Osijek, Croatia, 31000
    • Clinical Hospital Centre Osijek
• Israel
  • HaMerkaz
    • Haifa, HaMerkaz, Israel, 3436212
      • Lady Davis Carmel Medical Center
    • Kfar Sava, HaMerkaz, Israel, 44281
      • Meir Medical Center
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 52621
      • Sheba Medical Center - PPDS
• Malaysia
  • Kajang, Malaysia, 43000
    • Hospital Serdang
  • Putrajaya, Malaysia, 62250
    • Hospital Putrajaya
  • Kuala Lumpur
    • Wilayah Persekutuan - Kuala Lumpur, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
• Philippines
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Mary Mediatrix Medical Center
  • Iloilo
    • Iloilo City, Iloilo, Philippines, 5000
      • St. Paul's Hospital
  • Pampanga
    • San Fernando City, Pampanga, Philippines, 2000
      • GreenCity Medical Center
• Poland
  • Warszawa, Poland, 02-637
    • Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. prof. dr hab. med. Eleonory Reicher
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy
  • Lódzkie
    • Łódź, Lódzkie, Poland, 90-153
      • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology Belgrade - PPDS
  • Krusevac, Serbia, 37000
    • General Hospital Krusevac
  • Niš, Serbia, 18000
    • University Clinical Center Niš
  • Novi Sad, Serbia, 21000
    • Clinical Centre of Vojvodina
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • University Clinical Center of Serbia - PPDS
• Spain
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Valencia, Spain, 46940
    • Hospital de Manises
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University
  • Krung Thep Maha Nakhon-Bangkok
    • Din Daeng, Krung Thep Maha Nakhon-Bangkok, Thailand, 10400
      • Rajavithi Hospital
    • Din Daeng, Krung Thep Maha Nakhon-Bangkok, Thailand, 10400
      • Ramathibodi Hospital Mahidol University
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-2110
      • University of Alabama at Birmingham
  • California
    • San Dimas, California, United States, 91773-3537
      • California Kidney Specialists
  • New York
    • Syracuse, New York, United States, 13210-2306
      • SUNY Upstate Medical University
  • Texas
    • El Paso, Texas, United States, 79925
      • Davita Clinical Research - El Paso
    • Houston, Texas, United States, 77090
      • Care and Cure Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daxdilimab Arm 1; Daxdilimab injections over a total of 104 weeks	Drug: Daxdilimab; Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734
Experimental: Daxdilimab Arm 2; Daxdilimab injections over a total of 104 weeks	Drug: Daxdilimab; Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734
Placebo Comparator: Placebo; Placebo injections over a total of 104 weeks	Drug: Placebo (Normal Saline); Placebo will be administered subcutaneously as two injections for each dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved CRR at Week 48 Through Week 52	CRR was defined as meeting all of the following: Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m^2 or no worse than 15% below Baseline; 24-hour urine protein to creatinine ratio (UPCR) ≤ 0.5 mg/mg; No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment	Week 48 to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Overall Renal Response (ORR) at Week 48 Through Week 52	CRR was defined as meeting all of the following: EGFR ≥ 60 mL/min/1.73 m^2 or no worse than 15% below Baseline; 24-hour UPCR ≤ 0.5 mg/mg; No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment Partial renal response (PRR) was defined as meeting all of the following: EGFR ≥ 60 mL/min/1.73 m^2 or no worse than 15% below Baseline; Improvement in 24-hour UPCR:For participants with a Baseline UPCR ≤ 3.0 mg/mg: < 1.0 mg/mgFor participants with a Baseline UPCR > 3.0 mg/mg: > 50% improvement from baseline and ≤ 3.0 mg/mg; No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment	Week 48 to Week 52
Change From Baseline in eGFR at Week 52	Change over time in the levels of eGRF present in the blood.	Baseline and Week 52
Proportion of Participants Achieving a Decrease in Daily Oral Corticosteroid (OCS) Dose of ≤ 2.5 mg Prednisone-Equivalent by Week 24 Maintained Through Week 52	Sustained reduction of OCS dose: Prednisone-equivalent dose ≤ 2.5 mg/day by Week 24 and not exceeding this dose through Week 52 and; No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment	Week 24 to Week 52
Serum Concentration of Daxdilimab	Levels of daxdilimab present in the blood serum at different time points.	Week 0 pre-dose, and 6 hours post-dose; Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 36
Number of Participants With Detectable Anti-Drug Antibodies (ADA) Against Daxdilimab	Assessed via blood test at multiple time points throughout the duration of the study.	Up to approximately 36 weeks
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant or clinical subject who was administered a pharmaceutical product, which may or may not have been causally related to the treatment. A serious AE (SAE) was any AE resulting in death, life-threatening situations, inpatient hospitalization or its prolongation, persistent/significant disability/incapacity, congenital abnormality/birth defect, or other significant medical events that may have jeopardized the participant or required medical/surgical intervention to prevent the outcomes listed above. Treatment-emergent AEs of special interest (AESI) included hypersensitivity reactions (e.g., anaphylaxis), severe viral infections/reactivations (Common Terminology for Adverse Events [CTCAE] Grade 3+), herpes zoster, opportunistic infections, and malignancies.	Up to approximately 36 weeks

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Actual): January 4, 2024
• Study Completion (Actual): January 4, 2024

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: HZNP-DAX-203; 2022-001377-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes