Clinical trial NCT04564339: Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lupus Nephritis
Immunoglobulin A Nephropathy
Keywords: glomerulonephritis
IGA
lupus nephritis
complement C5
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Assessed Using 24-hour Urine Collections
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50 Assessed Using 24-hour Urine Collections
timeFrame: Baseline, Week 50
measure: Both Cohorts: Change In Estimated Glomerular Filtration Rate (eGFR) From Baseline At Week 26 And Week 50
timeFrame: Baseline, Week 26, Week 50
measure: LN Cohort: Percentage Of Participants Meeting The Criteria For Complete Renal Response
timeFrame: Week 26 and Week 50
measure: LN Cohort: Percentage Of Participants Meeting The Criteria For Partial Renal Response
timeFrame: Week 26 and Week 50
measure: LN Cohort: Time To Urine Protein To Creatinine Ratio < 0.5 g/g
timeFrame: Baseline through Week 50
measure: LN Cohort: Percentage Of Participants Achieving Corticosteroid Taper To 7.5 mg/day
timeFrame: Week 14, Week 26, and Week 50
measure: LN Cohort: Percentage Of Participants With Renal Flare
timeFrame: Baseline through Week 50
measure: LN Cohort: Percentage Of Participants With Extrarenal Systemic Lupus Erythematosus Flare
timeFrame: Baseline through Week 50
measure: IgAN Cohort: Percentage Of Participants Meeting The Criteria For Partial Remission
timeFrame: Week 26 and Week 50
Other outcomes:
Locations:
city: S. Gate
country: United States
facility: Research Site
state: California
city: San Dimas
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Plantation
country: United States
facility: Research Site
state: Florida
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Herston
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: London
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Clermont Ferrand
country: France
facility: Research Site
city: Le Kremlin-Bicêtre
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Saint-Priest-en-Jarez
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Lérida
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Edgbaston
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
Study officials:
References: