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

Alexion Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Immunoglobulin A Nephropathy; Lupus Nephritis

Treatments: Drug: Placebo; Drug: Ravulizumab; Other: Background Therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT04564339

ALXN1210-NEPH-202

Details and patient eligibility

About

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).

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 4 patient groups, including a placebo group

Ravulizumab: LN Cohort

Experimental group

Description:

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.

Treatment:

Other: Background Therapy

Drug: Ravulizumab

Placebo: LN Cohort

Placebo Comparator group

Description:

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.

Treatment:

Other: Background Therapy

Drug: Placebo

Ravulizumab: IgAN Cohort

Experimental group

Description:

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.

Treatment:

Other: Background Therapy

Drug: Ravulizumab

Placebo: IgAN Cohort

Placebo Comparator group

Description:

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.

Treatment:

Other: Background Therapy

Drug: Placebo

Drug: Ravulizumab