Lupus nephritis Skin and Connective Tissue Diseases
Conditions
Interventions
Crovalimab: Participants will receive crovalimab, intravenously (IV), at an initial loading dose of 1000 mg or 1500 mg on Day 1, based on the participant’s body weight of =40 kg to <100 kg or =100 kg
Sponsors
F. Hoffmann-La Roche
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 27/04/2023: 1. Age 18 - 65 years at the time of signing the Informed Consent Form 2. Body weight =40 kg at screening 3. Active LN, as evidenced by either: 1) A kidney biopsy demonstrating active proliferative (Class III or IV) and/or membranous (Class V) LN, performed within 12 months of screening or during screening; or 2) biopsy-proven Class III, IV, and/or V LN at anytime before screening and an active LN flare, as determined by the investigator, requiring the equivalent of at least 0.5 mg/kg/day of prednisone during screening. 4. UPCR =1.5 g/g on a 24-hour urine collection at screening 5. Vaccination against Neisseria meningitidis (N. meningitidis) serotypes A, C, W, and Y <3 years prior to initiation of study treatment 6. Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae according to national vaccination recommendations Previous participant inclusion criteria as of 06/12/2022: 1. Age 18 - 65 years at the time of signing the Informed Consent Form 2. Body weight =40 kg at screening 3. Active LN, as evidenced by a kidney biopsy demonstrating active proliferative (Class III or IV) and/or membranous (Class V) LN, performed within 12 months of screening or during screening 4. UPCR =1.5 g/g on a 24-hour urine collection at screening 5. Vaccination against Neisseria meningitidis (N. meningitidis) serotypes A, C, W, and Y <3 years prior to initiation of study treatment 6. Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae according to national vaccination recommendations Previous participant inclusion criteria: 1. Age 18 - 65 years at the time of signing the Informed Consent Form 2. Body weight =40 kg at screening 3. Active LN, as evidenced by a kidney biopsy demonstrating active proliferative (Class III or IV) and/or membranous (Class V) LN, performed within 12 months of screening or during screening 4. UPCR = 1.5 g/g on a 24-hour urine collection at screening 5. Vaccination against Neisseria meningitidis (N. meningitidis) <3 years prior to initiation of study treatment 6. Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae according to national vaccination recommendations
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 06/12/2022: 1. Pregnant or breastfeeding or intending to become pregnant during the study or within 46 weeks after the final dose of crovalimab or within 6 weeks after the final dose of mycopenolate mofetil (MMF), whichever is longer 2. Severe renal impairment, as defined by estimated glomerular filtration rate < 15 millimetres per minute per 1.73 metres square (mL/min/1.73 m²), need for dialysis or renal transplantation 3. Presence of rapidly-progressive glomerulonephritis 4. Active or evolving multisystem organ dysfunction or failure 5. Known or suspected hereditary complement deficiency 6. History of N. meningitidis infection within 6 months prior to screening and up to the first drug administration 7. History of serious recurrent or chronic infection 8. Known or suspected immune deficiency 9. Positive Human immunodeficiency virus (HIV) test or known HIV infection 10. Splenectomy < 6 months prior to screening 11. Participants who have a history of malignancy within 5 years prior to screening and up to the first dose of study treatment 12. History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in crovalimab, including hypersensitivity to human, humanized, or murine monoclonal antibodies or known hypersensitivity to any constituent of the product, or to corticosteroids or MMF 13. Current, previous or expected future treatment with a complement inhibitor within 46 weeks after the final crovalimab administration 14. Lack of peripheral venous access 15. Any condition requiring plasmapheresis Previous participant exclusion criteria: 1. Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the final dose of crovalimab or within 6 weeks after the final dose of mycopenolate mofetil (MMF), whichever is longer 2. Severe renal impairment, as defined by estimated glomerular filtration rate < 15 millimetres per minute per 1.73 metres square (mL/min/1.73 m²), need for dialysis or renal transplantation 3. Presence of rapidly-progressive glomerulonephritis 4. Active or evolving multisystem organ dysfunction or failure 5. Known or suspected hereditary complement deficiency 6. History of N. meningitidis infection within 6 months prior to screening and up to the first drug administration 7. History of serious recurrent or chronic infection 8. Known or suspected immune deficiency 9. Positive Human immunodeficiency virus (HIV) test or known HIV infection 10. Splenectomy < 6 months prior to screening 11. Participants who have a history of malignancy within 5 years prior to screening and up to the first dose of study treatment 12. History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in crovalimab, including hypersensitivity to human, humanized, or murine monoclonal antibodies or known hypersensitivity to any constituent of the product, or to corticosteroids or MMF 13. Current, previous or expected future treatment with a complement inhibitor within 6 months after the final crovalimab administration 14. Lack of peripheral venous access 15. Any condition requiring plasmapheresis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 06/12/2022: 1. Maximum observed serum concentration (Cmax) of crovalimab measured using serum samples at specified timepoints from baseline up to 12 weeks after the final dose of study treatment (up to Week 32) 2. Minimum observed serum concentrations (Cmin) of crovalimab measured using serum samples at specified timepoints from baseline up to 12 weeks after the final dose of study treatment (up to Week 32) 3. Trough serum concentration (Ctrough) of crovalimab measured using serum sample at Week 24 4. Incidence of adverse events (AEs) and severity of AEs determined according to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) from screening up to the long-term follow-up telephone visit at Week 66 5. Change in targeted vital signs, including temperature, systolic and diastolic blood pressure, pulse and respiratory rate, from baseline to the long-term follow-up in-person visit at Week 52 6. Change in targeted clinical laboratory test results measured using serum samples from baseline to the long-term follow-up visit in-person at Week 52 7. Percentage of participants with severity of injection-site reactions, infusion-related reactions, hypersensitivity, and infections (including Meningococcal Meningitis) from baseline up to the long-term follow-up visit in-person at Week 52 8. Percentage of participants with AEs leading to crovalimab discontinuation from baseline up to week 24 Previous primary outcome measures: 1. Maximum observed serum concentration (Cmax) of crovalimab measured using serum samples at specified timepoints from baseline up to 12 weeks after the final dose of study treatment (up to Week 32) 2. Minimum observed serum concentrations (Cmin) of crovalimab measured using serum samples at specified timepoints from baseline up to 12 weeks after the final dose of study treatment (up to Week 32) 3. Trough serum concentration (Ctrough) of crovalimab measured using serum | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 06/12/2022: 1. Percentage of participants with serum anti-drug antibodies (ADAs) measured from serum samples collected at baseline (Day 1) and incidence of ADAs during the study 2. Change over time in PD biomarker-free complement component 5 (C5) measured from serum samples to assess the biologic activity of crovalimab treatment i.e., to measure the interaction of crovalimab against the drug target C5 from baseline (Day 1) up to the long-term follow-up visit (up to Week 52) 3. Change over time in PD biomarkers, including free C5 serum concentrations and CH50 (complement activity) as measured by Liposome Immunoassay (LIA), to assess the biologic activity of crovalimab from baseline (Day 1) up to the long-term follow-up visit (up to Week 52) Previous secondary outcome measures: 1. Percentage of participants with anti-drug antibodies (ADAs) measured from the serum samples at baseline (Day 1) up to 12 weeks after the final dose of study treatment (up to Week 32) 2. Change over time in PD biomarker-free complement component 5 (C5) measured from serum samples to assess the biologic activity of crovalimab treatment i.e., to measure the interaction of crovalimab against the drug target C5 From baseline (Day 1) up to the long-term follow-up visit (up to Week 48) 3. Change over time in PD biomarker- CH50 (complement activity) as measured by Liposome Immunoassay (LIA), in serum to assess the biologic activity of crovalimab treatment i.e., to monitor total complement activity from baseline (Day 1) up to the long-term follow-up visit (up to Week 48) | — |
Countries
Argentina, Colombia, Germany, Italy, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed