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

• ClinicalTrials.gov Identifier: NCT05540665
• Recruitment Status: Terminated
• First Posted: September 15, 2022
• Last Update Posted: May 3, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: September 12, 2022
• First Posted Date: September 15, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: April 26, 2023
• Actual Primary Completion Date: January 4, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 12, 2022): Proportion of participants achieving complete renal response (CRR) at Week 48 and sustained through Week 52. [ Time Frame: Week 48 to Week 52 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 1, 2022)

• Proportion of participants achieving overall renal response (ORR) at Week 48 and sustained through Week 52. [ Time Frame: Week 48 to Week 52 ]
• Change from baseline in estimated glomerular filtration rate (eGFR) at Week 52. [ Time Frame: Day 1 to Week 52 ]
• Proportion of participants able to taper oral corticosteroids (OCS) to target by Week 24 and maintain target dose through Week 52. [ Time Frame: Week 24 to Week 52 ]
• Anti-Drug Antibody (ADA) rate. [ Time Frame: Day 1 to Week 116 ]
• Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent adverse events of special interest (AESIs). [ Time Frame: Day 1 to Week 116 ]

Original Secondary Outcome Measures (submitted: September 12, 2022)

• Proportion of participants achieving overall renal response (ORR) at Week 48 and sustained through Week 52. [ Time Frame: Week 48 to Week 52 ]
• Change from baseline in eGFR at Week 52. [ Time Frame: Day 1 to Week 52 ]
• Proportion of participants able to taper oral corticosteroids (OCS) to target by Week 24 and maintain target dose through Week 52. [ Time Frame: Week 24 to Week 52 ]
• Anti-Drug Antibody (ADA) rate. [ Time Frame: Day 1 to Week 116 ]
• Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent adverse events of special interest (AESIs). [ Time Frame: Day 1 to Week 116 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Lupus Nephritis

Intervention

• 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.

Study Arms

• Experimental: Daxdilimab Arm 1
  Daxdilimab injections over a total of 104 weeks
  Intervention: Drug: Daxdilimab
• Experimental: Daxdilimab Arm 2
  Daxdilimab injections over a total of 104 weeks
  Intervention: Drug: Daxdilimab
• Placebo Comparator: Placebo
  Placebo injections over a total of 104 weeks
  Intervention: Drug: Placebo (Normal Saline)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 8, 2023): 19
• Original Estimated Enrollment (submitted: September 12, 2022): 210
• Actual Study Completion Date: January 4, 2024
• Actual Primary Completion Date: January 4, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Croatia, Israel, Malaysia, Philippines, Poland, Serbia, Spain, Taiwan, Thailand, United States

Administrative Information

• NCT Number: NCT05540665
• Other Study ID Numbers: HZNP-DAX-203; 2022-001377-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: http://amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Horizon Therapeutics Ireland DAC
• Current Study Sponsor: Amgen
• Original Study Sponsor: Horizon Therapeutics Ireland DAC
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: May 2024