Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) (SANCTUARY)

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

The objectives of this study are to evaluate the safety and efficacy of ravulizumab administered by intravenous (IV) infusion compared to placebo and demonstrate proof-of-concept of the efficacy of terminal complement inhibition in participants with LN (LN Cohort) or IgAN (IgAN Cohort).

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis; Immunoglobulin A Nephropathy
• Intervention / Treatment: Drug: Ravulizumab; Other: Background Therapy; Drug: Placebo

Detailed Description

This study consists of a 6-week Screening Period, 26-week Initial Evaluation Period, a 24-week Extension Period, and a 36-week post-treatment Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, 4029
    • Research Site
  • Parkville, Australia, 3050
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Research Site
    • Québec, Quebec, Canada, G1R 2J6
      • Research Site
• France
  • Clermont-Ferrand, France, 63003
    • Research Site
  • Le Kremlin-Bicêtre, France, 94270
    • Research Site
  • Paris, France, 75020
    • Research Site
  • Saint-Priest-en-Jarez, France, 42270
    • Research Site
  • Strasbourg, France, 67091
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Hanover, Germany, 30625
    • Research Site
  • Lübeck, Germany, 23538
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Brescia, Italy, 25123
    • Research Site
  • Florence, Italy, 50134
    • Research Site
  • Torino, Italy, 10154
    • Research Site
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Research Site
• Poland
  • Lodz, Poland, 92-213
    • Research Site
• South Korea
  • Anyang-si, South Korea, 14068
    • Research Site
  • Seongnam-si, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 134-727
    • Research Site
  • Seoul, South Korea, 6591
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Lleida, Spain, 25198
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Palma de Mallorca, Spain, 07010
    • Research Site
  • Seville, Spain, 41013
    • Research Site
  • Valencia, Spain, 46017
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Research Site
  • Kaohsiung City, Taiwan, 833401
    • Research Site
  • New Taipei City, Taiwan, 23561
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
• United Kingdom
  • Edgbaston, United Kingdom, B15 2WB
    • Research Site
  • London, United Kingdom, SE1 7EH
    • Research Site
  • London, United Kingdom, W12 0HS
    • Research Site
  • Salford, United Kingdom, M6 8HD
    • Research Site
• United States
  • California
    • San Dimas, California, United States, 91773
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
    • South Gate, California, United States, 90280
      • Research Site
    • Stanford, California, United States, 94305
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32835
      • Research Site
    • Plantation, Florida, United States, 33324
      • Research Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Research Site
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
  • New York
    • New York, New York, United States, 10003
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Research Site
  • Texas
    • El Paso, Texas, United States, 79935
      • Research Site
    • Houston, Texas, United States, 77054
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Common to both disease cohorts:

• Proteinuria ≥1 (gram [g]/day or g/g)
• Vaccinated against meningococcal infection
• Vaccinated for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to national/local regulatory requirements

For LN cohort:

• Diagnosis of active focal or diffuse proliferative LN Class III or IV
• Clinically active LN, requiring/receiving immunosuppression induction treatment

For IgAN cohort:

• Diagnosis of primary IgAN
• Compliance with stable and optimal dose of renin-angiotensin system inhibitor treatment for ≥ 3 months

Exclusion Criteria:

Common to both disease cohorts:

• eGFR < 30 milliliters/minute/1.73 meters squared
• Previously received a complement inhibitor (for example, eculizumab)
• Concomitant significant renal disease other than LN or IgAN
• History of other solid organ or bone marrow transplant
• Uncontrolled hypertension

For IgAN cohort:

• Diagnosis of rapid progressive glomerulonephritis
• Prednisone or prednisone equivalent > 20 milligram (mg) per day for > 14 consecutive days or any other immunosuppression within 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ravulizumab: LN Cohort; Eligible participants will receive ravulizumab IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.	Drug: Ravulizumab; Dosages (loading and maintenance) will be based on the participant's body weight.; Other Names: Ultomiris; Other: Background Therapy; Participants will receive background therapy consistent with the standard of care.
Placebo Comparator: Placebo: LN Cohort; Eligible participants will receive placebo IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.	Other: Background Therapy; Participants will receive background therapy consistent with the standard of care.; Drug: Placebo; Dosages (loading and maintenance) will be based on the participant's body weight.
Experimental: Ravulizumab: IgAN Cohort; Eligible participants will receive ravulizumab IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.	Drug: Ravulizumab; Dosages (loading and maintenance) will be based on the participant's body weight.; Other Names: Ultomiris; Other: Background Therapy; Participants will receive background therapy consistent with the standard of care.
Placebo Comparator: Placebo: IgAN Cohort; Eligible participants will receive placebo IV infusion in combination with background therapy during the Initial Evaluation Period (26 weeks) and will switch to ravulizumab for the Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.	Drug: Ravulizumab; Dosages (loading and maintenance) will be based on the participant's body weight.; Other Names: Ultomiris; Other: Background Therapy; Participants will receive background therapy consistent with the standard of care.; Drug: Placebo; Dosages (loading and maintenance) will be based on the participant's body weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IgAN Cohort: Percentage Change From Baseline in Proteinuria at Week 26 Measured by Absolute Protein (Based on 24-hour Urine Collections)	Proteinuria, the presence of excess proteins in the urine, was measured by absolute protein in grams/day derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.	Baseline, Week 26
LN Cohort: Percentage Change From Baseline in Proteinuria at Week 26 Measured by Urine Protein to Creatinine Ratio (UPCR) (Based on 24-hour Urine Collections)	Proteinuria, the presence of excess proteins in the urine, was measured by UPCR in grams/gram derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IgAN Cohort: Percentage Change From Baseline in Proteinuria at Week 50 Measured by Absolute Protein (Based on 24-hour Urine Collections)	Proteinuria, the presence of excess proteins in the urine, was measured by absolute protein in grams/day derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.	Baseline, Week 50
LN Cohort: Percentage Change From Baseline in Proteinuria at Week 50 Measured by UPCR (Based on 24-hour Urine Collections)	Proteinuria, the presence of excess proteins in the urine, was measured by UPCR in grams/gram derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.	Baseline, Week 50
IgAN Cohort: Percentage of Participants With > 30% and > 50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline Assessed Using 24-hour Urine Collections	Proteinuria, the presence of excess proteins in the urine, was measured by absolute protein in grams/day derived from 24-hour urine collections obtained at designated timepoints.	Baseline to Week 26 and Week 50
LN Cohort: Percentage of Participants With > 30% and > 50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline Assessed Using 24-hour Urine Collections	Proteinuria, the presence of excess proteins in the urine, was measured by UPCR in grams/gram derived from 24-hour urine collections obtained at designated timepoints.	Baseline to Week 26 and Week 50
IgAN Cohort: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26 and Week 50	Changes in kidney function were monitored using measurements of eGFR and calculated based on the Chronic Kidney Disease Epidemiology Collaboration formula. Results are reported in milliliters/minute/1.73 meters squared (mL/min/1.73 m^2). Estimates of change from baseline are least-square means based on a mixed-effect model for repeated measures model that included change from baseline as the response variable, treatment as independent variable and adjusts for covariates of baseline and the stratification factor at randomization. An increase in eGFR in response to treatment indicated a reduction in symptoms.	Baseline, Week 26 and Week 50
LN Cohort: Change From Baseline in eGFR at Week 26 and Week 50	Changes in kidney function were monitored using measurements of eGFR and calculated based on the Chronic Kidney Disease Epidemiology Collaboration formula. Results are reported in mL/min/1.73 m^2. Estimates of change from baseline are least-square means based on a mixed-effect model for repeated measures model that included change from baseline as the response variable, treatment as independent variable and adjusts for covariates of baseline and the stratification factor at randomization. An increase in eGFR in response to treatment indicated a reduction in symptoms.	Baseline, Week 26 and Week 50
IgAN Cohort: Change From Baseline in Serum Complement Component 3 (C3) and Complement Component 4 (C4) Concentrations at Week 26 and Week 50		Baseline, Week 26 and Week 50
LN Cohort: Change From Baseline in Serum C3 and C4 Concentrations at Week 26 and Week 50		Baseline, Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Complete Renal Response (CRR)	The CRR was defined as meeting all 3 of the following criteria: - UPCR ≤0.5 gram/gram (g/g); - eGFR >60 mL/min/1.73 m^2 or no eGFR reduction ≥20% from baseline; and - no treatment failure. Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal systemic lupus erythematosus (SLE) flare, or suboptimal response.	Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Partial Renal Response (PRR)	The PRR was defined as meeting all 3 of the following criteria: - decrease of UPCR >50% from baseline; - eGFR >60 mL/min/1.73 m^2 or no eGFR reduction ≥20% from baseline; and - no treatment failure. Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal SLE flare, or suboptimal response.	Week 26 and Week 50
LN Cohort: Time to Urine Protein to Creatinine Ratio (UPCR) < 0.5 g/g, as Measured by Spot Urine Samples		Baseline through Week 50
LN Cohort: Percentage of Participants Achieving Corticosteroid Taper to 7.5 Milligrams (mg)/Day	A corticosteroid taper was carried out per protocol at the clinical discretion of the investigator.	Week 14, Week 26, and Week 50
LN Cohort: Percentage of Participants With Renal Flare	Renal flare was determined in the opinion of the investigator and additional protocol-specified criteria. For participants who achieved a CRR, a renal flare was the reproducible recurrence of proteinuria ≥1g/g. For all other participants, a renal flare was either of the following: a reproducible increase of serum creatinine >25% higher than baseline, above the upper limit of normal (plus additional protocol-specified criteria), or a reproducible doubling of the UPCR from a 24-hour urine collection compared with the lowest previous value obtained after the first dose of study intervention.	Baseline through Week 50
LN Cohort: Percentage of Participants With Extrarenal Systemic Lupus Erythematosus (SLE) Flare	Extrarenal SLE flare was defined as an increase in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Safety of Estrogens in Lupus Erythematosus National Assessment modification ≥4 points that was not accounted for by proteinuria, hematuria, urinary cellular casts, hypocomplementemia, or an increase in anti-double-stranded DNA antibody level. The SLEDAI-2K is an instrument that was used to assess the disease activity of extrarenal SLE flare across 18 disease descriptors. Each descriptor carried a weighted value ranging from 1-8, with the reported score calculated as the sum of these descriptors and ranging from 0 to 85. Higher scores represent increased degrees of disease activity.	Baseline through Week 50
LN Cohort: Percentage of Participants With Treatment Failure	Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal SLE flare, or suboptimal response.	Baseline through Week 50
LN Cohort: Percentage of Participants With Suboptimal Response	A suboptimal response was to be determined in the opinion of the investigator in addition to the following criterion: reproducible proteinuria ≤25% decreased compared to baseline based on UPCR on a 24-hour urine collection performed by a central laboratory.	Baseline through Week 50
LN Cohort: Change From Baseline in Serum Albumin at Week 26 and Week 50	For the determination of serum albumin, blood samples were obtained at designated time points.	Baseline, Week 26, Week 50
IgAN Cohort: Percentage of Participants Meeting the Criteria for Partial Remission	Partial remission was defined as mean proteinuria <1 g/24 hours, based on two valid 24-hour urine collections obtained within 2 weeks prior to the study visit.	Week 26 and Week 50

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.
• Lafayette R, Tumlin J, Fenoglio R, Kaufeld J, Perez Valdivia MA, Wu MS, Susan Huang SH, Alamartine E, Kim SG, Yee M, Kateifides A, Rice K, Garlo K, Barratt J; SANCTUARY Study Investigators. Efficacy and Safety of Ravulizumab in IgA Nephropathy: A Phase 2 Randomized Double-Blind Placebo-Controlled Trial. J Am Soc Nephrol. 2025 Apr 1;36(4):645-656. doi: 10.1681/ASN.0000000534. Epub 2024 Oct 25.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Actual): March 26, 2025
• Study Completion (Actual): August 18, 2025

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: lupus nephritis; glomerulonephritis; IGA; complement C5
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic; Nephritis; Skin and Connective Tissue Diseases; Lupus Nephritis; Glomerulonephritis; Glomerulonephritis, IGA; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; ravulizumab
• Other Study ID Numbers: ALXN1210-NEPH-202; 2020-001537-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No