Study of Ravulizumab in Immunoglobulin A Nephropathy (IgAN) (ICAN)

Alexion Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Immunoglobulin A Nephropathy; IgAN

Treatments: Drug: Placebo; Drug: Ravulizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06291376

D928FC00001

Details and patient eligibility

About

The primary objective of this study to evaluate efficacy of ravulizumab compared with placebo on proteinuria reduction and change in eGFR in adult participants with IgAN who are at risk of disease progression.

Full description

The I CAN study will enroll approximately 510 eligible participants with IgAN who are high risk of disease progression. Participants will be on stable concomitant IgAN treatment(s) consistent with standard of care for patients with IgAN for at least 3 months prior to Screening. Approximately 450 participants will be randomized in a 1:1 allocation ratio to receive a weight-based IV infusion of either ravulizumab or placebo. An interim analysis may be conducted at Week 34 to evaluate change in proteinuria and the final analysis will be conducted at Week 106 to evaluate eGFR. In addition, approximately 60 participants with eGFR 20-29 mL/min/1.73m2 will be enrolled in an Advanced Kidney Disease (AdKD) Cohort After Week 106, all participants have the option to enter an Open-label Ravulizumab Access Period.

Enrollment: 510 estimated patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documentation of IgAN diagnosis established on kidney biopsy obtained any time prior to or during the Screening Period for participants with eGFR ≥ 30 mL/min/1.73 m^2.
• For participants in the AdKD cohorts, eGFR 20 to 29 mL/min/1.73 m2 a kidney biopsy is required within 6 months prior to Screening or during the Screening Period.
• UPCR ≥ 0.75 g/g or UP ≥1 g/day calculated from the mean of two 24-hour urine during the Screening Period.
• Estimated GFR ≥ 30 mL/min/1.73 m2 at Screening.
• Stable and maximum allowed or tolerated RASI (ACEI and/or ARB) dose for ≥ 3 months prior to Screening with no planned change during Screening through Week 106.
• Participants who are receiving SGLT2I, DEARA, MRA or ERA must be on a stable and maximum allowed or tolerated dose for ≥ 3 months prior to Screening with no planned change in dose through Week 106.

Exclusion criteria

• Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss ≥ 50% over a period of 3 months prior to Screening.
• Secondary IgAN (eg, due to systemic lupus erythematosus (SLE), cirrhosis, or celiac disease; IgAV-N may be eligible).
• Concomitant clinically significant renal disease other than IgAN.
• Prior use of immunosuppressive treatment within 3 months of screening.
• Uncontrolled diabetes mellitus with glycosylated hemoglobin (HbA1c) > 8.5%.
• Henoch-Schonlein purpura (IgAV) requiring systemic immunosuppressive therapy within 12 months of Screening.
• History of kidney transplant or planned kidney transplant during the Treatment Period.
• Splenectomy or functional asplenia.
• History of Neisseria meningitidis infection.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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510 participants in 2 patient groups, including a placebo group

Ravulizumab IV q8w

Experimental group

Description:

Participants will receive a weight-based loading dose on Day 1 followed by weight-based maintenance dosing initiated on Day 15, and then administered every 8 weeks (q8w).

Treatment:

Drug: Ravulizumab

Placebo IV q8w

Placebo Comparator group

Description:

Participants will receive a weight-based loading dose on Day 1 followed by weight-based maintenance dosing initiated on Day 15, and then administered q8w.

Treatment:

Drug: Placebo