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

• ClinicalTrials.gov Identifier: NCT04564339
• Recruitment Status: Recruiting
• First Posted: September 25, 2020
• Last Update Posted: March 23, 2023
• Sponsor: Alexion
• Information provided by (Responsible Party): Alexion

Tracking Information

• First Submitted Date: September 21, 2020
• First Posted Date: September 25, 2020
• Last Update Posted Date: March 23, 2023
• Actual Study Start Date: December 11, 2020
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 21, 2020): Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Assessed Using 24-hour Urine Collections [ Time Frame: Baseline, Week 26 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 21, 2020)

• Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50 Assessed Using 24-hour Urine Collections [ Time Frame: Baseline, Week 50 ]
• Both Cohorts: Change In Estimated Glomerular Filtration Rate (eGFR) From Baseline At Week 26 And Week 50 [ Time Frame: Baseline, Week 26, Week 50 ]
• LN Cohort: Percentage Of Participants Meeting The Criteria For Complete Renal Response [ Time Frame: Week 26 and Week 50 ]
  Complete renal response will be determined by assessing proteinuria on 24-hour urine collections, eGFR levels, and no treatment failure.
• LN Cohort: Percentage Of Participants Meeting The Criteria For Partial Renal Response [ Time Frame: Week 26 and Week 50 ]
  Partial renal response will be determined by assessing proteinuria on 24-hour urine collections, eGFR levels, and no treatment failure.
• LN Cohort: Time To Urine Protein To Creatinine Ratio < 0.5 g/g [ Time Frame: Baseline through Week 50 ]
• LN Cohort: Percentage Of Participants Achieving Corticosteroid Taper To 7.5 mg/day [ Time Frame: Week 14, Week 26, and Week 50 ]
• LN Cohort: Percentage Of Participants With Renal Flare [ Time Frame: Baseline through Week 50 ]
• LN Cohort: Percentage Of Participants With Extrarenal Systemic Lupus Erythematosus Flare [ Time Frame: Baseline through Week 50 ]
• IgAN Cohort: Percentage Of Participants Meeting The Criteria For Partial Remission [ Time Frame: Week 26 and Week 50 ]
  Partial remission will be determined by assessing proteinuria on 24-hour urine collections.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment

Condition

• Lupus Nephritis
• Immunoglobulin A Nephropathy

Intervention

• Drug: Ravulizumab
  Dosages (loading and maintenance) will be based on the participant's body weight.
  Other Name: Ultomiris
• Drug: Placebo
  Dosages (loading and maintenance) will be based on the participant's body weight.
• Other: Background Therapy
  Participants will receive background therapy consistent with the standard of care.

Study Arms

• 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.
  Interventions:

  • Drug: Ravulizumab
  • Other: Background Therapy
• 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.
  Interventions:

  • Drug: Placebo
  • Other: Background Therapy
• 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.
  Interventions:

  • Drug: Ravulizumab
  • Other: Background Therapy
• 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.
  Interventions:

  • Drug: Ravulizumab
  • Drug: Placebo
  • Other: Background Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 21, 2020): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2025
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alexion Pharmaceuticals, Inc.; 855-752-2356; clinicaltrials@alexion.com

• Listed Location Countries: Australia, Canada, France, Germany, Italy, Korea, Republic of, Netherlands, Poland, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04564339
• Other Study ID Numbers: ALXN1210-NEPH-202; 2020-001537-13 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Alexion
• Original Responsible Party: Same as current
• Current Study Sponsor: Alexion
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Alexion
• Verification Date: March 2023