Clinical trial NCT05540665: Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lupus Nephritis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-09-15
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved CRR at Week 48 Through Week 52
timeFrame: Week 48 to Week 52
Secondary outcomes:
measure: Percentage of Participants Who Achieved Overall Renal Response (ORR) at Week 48 Through Week 52
timeFrame: Week 48 to Week 52
measure: Change From Baseline in eGFR at Week 52
timeFrame: Baseline and Week 52
measure: 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
timeFrame: Week 24 to Week 52
measure: Serum Concentration of Daxdilimab
timeFrame: 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
measure: Number of Participants With Detectable Anti-Drug Antibodies (ADA) Against Daxdilimab
timeFrame: Up to approximately 36 weeks
measure: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 36 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Dimas
country: United States
facility: California Kidney Specialists
state: California
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: El Paso
country: United States
facility: DaVita Clinical Research - El Paso
state: Texas
city: Houston
country: United States
facility: Care and Cure Clinic
state: Texas
city: La Plata
country: Argentina
facility: Framingham Centro Médico
state: Buenos Aires
city: Rosario
country: Argentina
facility: Instituto Médico de la Fundación Estudios Clínicos
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: DOM Centro de Reumatologia
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Swiss Medical Center Barrio Parque
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Aprillus Asistencia e Investigacion de Arcis Salud SRL
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Consultorios Médicos Dr. Doreski
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Médicas Tucumán
city: San Miguel De Tucumán
country: Argentina
facility: Clinica Mayo de U.M.C.B. S.R.L
city: Salvador
country: Brazil
facility: SER - Serviços Especializados em Reumatologia da Bahia S/S - ME
state: Bahia
city: Salvador
country: Brazil
facility: Clinica Senhor Do Bonfim CSB
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de Belo Horizonte - PPDS
state: Minas Gerais
city: Juiz De Fora
country: Brazil
facility: Centro Mineiro de Pesquisa
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: LMK Servicos Medicos SS
state: Rio Grande Do Sul
city: Cuiabá
country: Brazil
facility: Oncovida- Centro de Onco-Hematologia de Mato Grosso
city: Ribeirão Preto
country: Brazil
facility: Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP - PPDS
city: Santo André
country: Brazil
facility: Praxis Pesquisa Medica
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
city: São Paulo
country: Brazil
facility: Praxis Pesquisa Medica
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
state: HaMerkaz
city: Kfar Sava
country: Israel
facility: Meir Medical Center
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS
state: Tel-Aviv
city: Wilayah Persekutuan - Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Kuala Lumpur
city: Kajang
country: Malaysia
facility: Hospital Serdang
city: Putrajaya
country: Malaysia
facility: Hospital Putrajaya
city: Lipa City
country: Philippines
facility: Mary Mediatrix Medical Center
state: Batangas
city: Iloilo City
country: Philippines
facility: St. Paul's Hospital
state: Iloilo
city: San Fernando City
country: Philippines
facility: GreenCity Medical Center
state: Pampanga
city: Łódź
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
state: Lódzkie
city: Warszawa
country: Poland
facility: Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Dr hab. Med. Eleonory Reicher
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia - PPDS
state: Beograd
city: Belgrade
country: Serbia
facility: Institute of Rheumatology Belgrade - PPDS
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Krusevac
country: Serbia
facility: General Hospital Krusevac
city: Niš
country: Serbia
facility: University Clinical Center Nis
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital de Manises
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Din Daeng
country: Thailand
facility: Rajavithi Hospital
state: Krung Thep Maha Nakhon-Bangkok
city: Din Daeng
country: Thailand
facility: Ramathibodi Hospital Mahidol University
state: Krung Thep Maha Nakhon-Bangkok
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: