Resumen

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).

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

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).

Criterios de exclusión

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.

Intervenciones

drug

Daxdilimab

Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734

drug

Daxdilimab

Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734

drug

Placebo (Normal Saline)

Placebo will be administered subcutaneously as two injections for each dose.

Ubicaciones

Framingham Centro Médico

La Plata, Buenos Aires, Argentina

Instituto Médico de la Fundación Estudios Clínicos

Rosario, Santa Fe Province, Argentina

DOM Centro de Reumatologia

Buenos Aires, Argentina

Aprillus Asistencia e Investigacion de Arcis Salud SRL

Buenos Aires, Argentina

Consultorios Médicos Dr. Doreski

Buenos Aires, Argentina

Swiss Medical Center Barrio Parque

Ciudad Autónoma Buenos Aires, Argentina

Centro de Investigaciones Médicas Tucumán

San Miguel de Tucumán, Argentina

Clinica Mayo de U.M.C.B. S.R.L

San Miguel de Tucumán, Argentina

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

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Daxdilimab

Daxdilimab

Placebo (Normal Saline)

Ubicaciones

Framingham Centro Médico

Instituto Médico de la Fundación Estudios Clínicos

DOM Centro de Reumatologia

Aprillus Asistencia e Investigacion de Arcis Salud SRL

Consultorios Médicos Dr. Doreski

Swiss Medical Center Barrio Parque

Centro de Investigaciones Médicas Tucumán

Clinica Mayo de U.M.C.B. S.R.L

Patrocinadores