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 the efficacy of ravulizumab compared with placebo to reduce proteinuria and slow the rate of eGFR decline in adult participants with IgAN who are at risk of disease progression.

Full description

The I CAN study will enroll approximately 450 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, 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 20 participants with eGFR 20-29 mL/min/1.73m2 will be enrolled in an Exploratory Cohort and will receive open label weight-based IV infusion of ravulizumab. After Week 106, all participants have the option to enter a post-study access period and receive open-label ravulizumab.

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.
• UPCR ≥ 0.75 g/g or UP ≥1 g/day from the mean of two 24-hour urine collections during Screening.
• Estimated GFR ≥ 30 mL/min/1.73 m2 at Screening.
• Exploratory Cohort: eGFR 20-29 mL/min/1.73 m2 at Screening. A kidney biopsy is required within 6 months prior to Screening or during the Screening Period.
• Presence of hematuria as defined by a positive result on urine dipstick for blood or ≥ 5 red blood cells (RBCs)/high power field microscopy on urine sediment during or within 3 months of 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 on an SGLT2I, ERA, or MRA must be on a stable and maximum allowed or tolerated dose for ≥ 3 months prior to Screening with no planned change 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).
• Concomitant clinically significant renal disease other than IgAN.
• Prior use of immunosuppressive treatment for IgAN within 6 months of screening.
• Uncontrolled diabetes mellitus with glycosylated hemoglobin (HbA1c) > 8.5%.
• Clinically active Henoch-Schonlein purpura (IgA vasculitis) requiring ongoing systemic immunosuppressive therapy at 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). Participants in the exploratory group will receive open-label weight based loading dose on Day 1 followed by open label weight based maintenance dose on Day 15 and q8weeks after.

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