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

Phase 2

Terminated

Conditions: Lupus Nephritis

Interventions: Drug: Placebo (Normal Saline)
Drug: Daxdilimab

Registration Number: NCT05540665

Lead Sponsor: Amgen

Brief 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).

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 19

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo (Normal Saline)	Placebo injections over a total of 104 weeks
Daxdilimab Arm 1	Daxdilimab	Daxdilimab injections over a total of 104 weeks
Daxdilimab Arm 2	Daxdilimab	Daxdilimab injections over a total of 104 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved CRR at Week 48 Through Week 52	Week 48 to 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

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Overall Renal Response (ORR) at Week 48 Through Week 52	Week 48 to 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/mg * For 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
Change From Baseline in eGFR at Week 52	Baseline and Week 52	Change over time in the levels of eGRF present in the blood.
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	Week 24 to 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
Serum Concentration of Daxdilimab	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	Levels of daxdilimab present in the blood serum at different time points.
Number of Participants With Detectable Anti-Drug Antibodies (ADA) Against Daxdilimab	Up to approximately 36 weeks	Assessed via blood test at multiple time points throughout the duration of the study.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	Up to approximately 36 weeks	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.

Trial Locations

Locations (51): Clinica Mayo de U.M.C.B. S.R.L
🇦🇷
San Miguel De Tucumán, Argentina
SER - Serviços Especializados em Reumatologia da Bahia S/S - ME
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Salvador, Bahia, Brazil
Irmandade Da Santa Casa de Misericordia de Porto Alegre
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Porto Alegre, Rio Grande Do Sul, Brazil
DOM Centro de Reumatologia
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Buenos Aires, Argentina
Sheba Medical Center - PPDS
🇮🇱
Ramat Gan, Tel-Aviv, Israel
Mary Mediatrix Medical Center
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Lipa City, Batangas, Philippines
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸
Barcelona, Spain
SUNY Upstate Medical University
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Syracuse, New York, United States
Clinica Senhor Do Bonfim CSB
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Salvador, Bahia, Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
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São Paulo, Brazil
Praxis Pesquisa Medica
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São Paulo, Brazil
Hospital Clinic de Barcelona
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Barcelona, Spain
Swiss Medical Center Barrio Parque
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Ciudad Autónoma Buenos Aires, Argentina
LMK Servicos Medicos SS
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Porto Alegre, Rio Grande Do Sul, Brazil
Oncovida- Centro de Onco-Hematologia de Mato Grosso
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Cuiabá, Brazil
Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP - PPDS
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Ribeirão Preto, Brazil
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
DaVita Clinical Research - El Paso
🇺🇸
El Paso, Texas, United States
Care and Cure Clinic
🇺🇸
Houston, Texas, United States
Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy
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Warszawa, Poland
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
California Kidney Specialists
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San Dimas, California, United States
Santa Casa de Misericórdia de Belo Horizonte - PPDS
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Belo Horizonte, Minas Gerais, Brazil
Centro Mineiro de Pesquisa
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Juiz De Fora, Minas Gerais, Brazil
Hospital Serdang
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Kajang, Malaysia
Hospital de Manises
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Valencia, Spain
Framingham Centro Médico
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La Plata, Buenos Aires, Argentina
Lady Davis Carmel Medical Center
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Haifa, HaMerkaz, Israel
University Clinical Center of Serbia - PPDS
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Belgrade, Beograd, Serbia
General Hospital Krusevac
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Krusevac, Serbia
Consultorios Médicos Dr. Doreski
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Ciudad Autónoma de Buenos Aires, Argentina
Centro de Investigaciones Médicas Tucumán
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San Miguel de Tucuman, Argentina
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
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Łódź, Lódzkie, Poland
University Clinical Center Nis
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Niš, Serbia
Clinical Centre of Vojvodina
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Novi Sad, Serbia
Rajavithi Hospital
🇹🇭
Din Daeng, Krung Thep Maha Nakhon-Bangkok, Thailand
Ramathibodi Hospital Mahidol University
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Din Daeng, Krung Thep Maha Nakhon-Bangkok, Thailand
Aprillus Asistencia e Investigacion de Arcis Salud SRL
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Ciudad Autónoma de Buenos Aires, Argentina
Clinical Hospital Centre Osijek
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Osijek, Croatia
Meir Medical Center
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Kfar Sava, HaMerkaz, Israel
GreenCity Medical Center
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San Fernando City, Pampanga, Philippines
Military Medical Academy
🇷🇸
Belgrade, Serbia
Chiang Mai University
🇹🇭
Chiang Mai, Thailand
University Malaya Medical Centre
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Wilayah Persekutuan - Kuala Lumpur, Kuala Lumpur, Malaysia
Hospital Putrajaya
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Putrajaya, Malaysia
St. Paul's Hospital
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Iloilo City, Iloilo, Philippines
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Dr hab. Med. Eleonory Reicher
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Warszawa, Poland
Institute of Rheumatology Belgrade - PPDS
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Belgrade, Serbia
China Medical University Hospital
🇨🇳
Taichung, Taiwan
Phramongkutklao Hospital
🇹🇭
Bangkok, Thailand
Instituto Médico de la Fundación Estudios Clínicos
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Rosario, Santa Fe, Argentina