NCT04564339

Brief Summary

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).

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
123

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2021

Typical duration for phase_2

Geographic Reach
12 countries

64 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 21, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 25, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

January 19, 2021

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 26, 2025

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 18, 2025

Completed
5 months until next milestone

Results Posted

Study results publicly available

January 22, 2026

Completed
Last Updated

January 22, 2026

Status Verified

January 1, 2026

Enrollment Period

4.2 years

First QC Date

September 21, 2020

Results QC Date

January 6, 2026

Last Update Submit

January 6, 2026

Conditions

Keywords

glomerulonephritisIGAlupus nephritiscomplement C5

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (18)

  • IgAN Cohort: Percentage Change From Baseline in Proteinuria at Week 50 Measured by Absolute Protein (Based on 24-hour Urine Collections)

    Baseline, Week 50

  • LN Cohort: Percentage Change From Baseline in Proteinuria at Week 50 Measured by UPCR (Based on 24-hour Urine Collections)

    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

    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

    Baseline to Week 26 and Week 50

  • IgAN Cohort: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26 and Week 50

    Baseline, Week 26 and Week 50

  • +13 more secondary outcomes

Study Arms (4)

Ravulizumab: LN Cohort

EXPERIMENTAL

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: RavulizumabOther: Background Therapy

Placebo: LN Cohort

PLACEBO COMPARATOR

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.

Drug: PlaceboOther: Background Therapy

Ravulizumab: IgAN Cohort

EXPERIMENTAL

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: RavulizumabOther: Background Therapy

Placebo: IgAN Cohort

PLACEBO COMPARATOR

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: RavulizumabDrug: PlaceboOther: Background Therapy

Interventions

Dosages (loading and maintenance) will be based on the participant's body weight.

Placebo: IgAN CohortPlacebo: LN Cohort

Dosages (loading and maintenance) will be based on the participant's body weight.

Also known as: Ultomiris
Placebo: IgAN CohortRavulizumab: IgAN CohortRavulizumab: LN Cohort

Participants will receive background therapy consistent with the standard of care.

Placebo: IgAN CohortPlacebo: LN CohortRavulizumab: IgAN CohortRavulizumab: LN Cohort

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (64)

Research Site

San Dimas, California, 91773, United States

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Research Site

Santa Monica, California, 90404, United States

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South Gate, California, 90280, United States

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Stanford, California, 94305, United States

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Orlando, Florida, 32835, United States

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Plantation, Florida, 33324, United States

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Lawrenceville, Georgia, 30046, United States

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Lexington, Kentucky, 40536, United States

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Louisville, Kentucky, 40202, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Kansas City, Missouri, 64111, United States

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New York, New York, 10003, United States

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Chapel Hill, North Carolina, 27599, United States

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Columbus, Ohio, 43203, United States

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El Paso, Texas, 79935, United States

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Houston, Texas, 77054, United States

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Herston, 4029, Australia

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Parkville, 3050, Australia

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Westmead, 2145, Australia

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London, Ontario, N6A 5W9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Québec, Quebec, G1R 2J6, Canada

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Clermont-Ferrand, 63003, France

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Le Kremlin-Bicêtre, 94270, France

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Paris, 75020, France

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Saint-Priest-en-Jarez, 42270, France

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Strasbourg, 67091, France

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Toulouse, 31059, France

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Berlin, 10117, Germany

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Essen, 45147, Germany

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Hanover, 30625, Germany

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Lübeck, 23538, Germany

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Bologna, 40138, Italy

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Brescia, 25123, Italy

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Florence, 50134, Italy

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Torino, 10154, Italy

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Maastricht, 6229 HX, Netherlands

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Lodz, 92-213, Poland

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Anyang-si, 14068, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 134-727, South Korea

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Seoul, 6591, South Korea

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Lleida, 25198, Spain

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Madrid, 28007, Spain

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Research Site

Madrid, 28040, Spain

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Madrid, 28041, Spain

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Málaga, 29010, Spain

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Palma de Mallorca, 07010, Spain

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Seville, 41013, Spain

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Valencia, 46017, Spain

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Zaragoza, 50009, Spain

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Kaohsiung City, 80756, Taiwan

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Research Site

Kaohsiung City, 833401, Taiwan

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Research Site

New Taipei City, 23561, Taiwan

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Research Site

Taichung, 40447, Taiwan

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Edgbaston, B15 2WB, United Kingdom

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Research Site

London, SE1 7EH, United Kingdom

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Research Site

London, W12 0HS, United Kingdom

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Research Site

Salford, M6 8HD, United Kingdom

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Lupus NephritisGlomerulonephritis, IGAGlomerulonephritis

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

NephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesLupus Erythematosus, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Limitations and Caveats

The LN cohort of the study was terminated early due to lack of efficacy.

Results Point of Contact

Title
Alexion Pharmaceuticals, Inc.
Organization
Alexion Pharmaceuticals, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Participants, all investigative site personnel, and any Alexion employee, or designee, directly associated with the conduct of the study will be blinded to participant treatment assignments during the 26-week Initial Evaluation Period. Both the participants and the investigative site personnel will remain blinded for the remaining 24-week Extension Period.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 21, 2020

First Posted

September 25, 2020

Study Start

January 19, 2021

Primary Completion

March 26, 2025

Study Completion

August 18, 2025

Last Updated

January 22, 2026

Results First Posted

January 22, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations