CROVALIMAB for Atypical hemolytic uremic syndrome (aHUS)

Inclusion criteria

• {"criterion_text":"- Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment in accordance with current local guidelines or standard of care, as applicable in patients with complement deficiency (for ALL cohorts)\n- For female patients of childbearing potential, an agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception (for ALL cohorts)\n- Onset of initial TMA presentation, within 28 days prior to the first dose of crovalimab (For naïve cohort only)\n- Clinical evidence of response to either eculizumab or ravulizumab, as documented by a platelet count ≥LLN, LDH ≤ULN, and stable (decrease or increase of ≤20%) or improving creatinine at two consecutive measurements at least 4 weeks apart prior to Week 1 Day 1 of crovalimab treatment. (For switch cohort only)\n- Known C5 polymorphism (e.g., Arg885) (For C5SNP cohort only)"}

Exclusion criteria

• {"criterion_text":"- TMA associated with non-aHUS-related renal disease\n- History of a kidney disease other than aHUS, affecting renal function\n- Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome\n- Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration\n- History of Neisseria meningitidis infection within 6 months of study enrollment\n- History of malignancy within 5 years prior to screening and up to the first crovalimab administration"}

Primary endpoints

• {"endpoint_text":"- 1. Proportion of patients with complete TMA response (cTMAr) anytime from baseline to Week 25 (after 24 weeks on treatment)","definition_or_measurement_approach":"Proportion of patients achieving complete TMA response (cTMAr) assessed any time from baseline through Week 25 (after 24 weeks on treatment)."}

Secondary endpoints

• {"endpoint_text":"- 1. Change from baseline to Week 25 in dialysis requirement status","definition_or_measurement_approach":"Change in dialysis requirement status from baseline to Week 25."}
• {"endpoint_text":"- 2. Observed value and change from baseline to Week 25 (after 24 weeks on treatment); in estimated glomerular filtration rate (eGFR)","definition_or_measurement_approach":"Observed eGFR value and change from baseline to Week 25 (after 24 weeks on treatment)."}
• {"endpoint_text":"- 3. Proportion of patients with change from baseline to Week 25 (after 24 weeks on treatment) in chronic kidney disease (CKD) stage classified as improved, stable (no change), or worsened based on the National Kidney Foundation Chronic Kidney Disease Stage","definition_or_measurement_approach":"Proportion of patients whose CKD stage (per NKF classification) is improved, stable, or worsened from baseline to Week 25."}
• {"endpoint_text":"- 4. Observed value and change from baseline to Week 25 (after 24 weeks on treatment) in hematologic parameters","definition_or_measurement_approach":"Observed hematologic parameter values and change from baseline to Week 25."}
• {"endpoint_text":"- 5. Incidence and severity of adverse events","definition_or_measurement_approach":"Incidence and severity grading of adverse events occurring during the study period."}
• {"endpoint_text":"- 6. Change in targeted vital signs and clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in pre-specified vital signs and clinical laboratory tests."}
• {"endpoint_text":"- 7. Incidence and severity of injection site reactions, infusion related reactions, hypersensitivity, malignant hypertension, and infections","definition_or_measurement_approach":"Incidence and severity of these specific adverse event categories recorded during treatment."}
• {"endpoint_text":"- 8. Incidence of adverse events leading to study drug discontinuation","definition_or_measurement_approach":"Count and description of AEs that result in permanent discontinuation of study drug."}
• {"endpoint_text":"- 9. Serum concentration of crovalimab","definition_or_measurement_approach":"Measured serum concentration of crovalimab at specified timepoints (PK assessments)."}
• {"endpoint_text":"- 10. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab","definition_or_measurement_approach":"Assessment of ADA prevalence and incidence via immunogenicity assays."}
• {"endpoint_text":"- 11. Proportion of patients with platelet count >= LLN","definition_or_measurement_approach":"Proportion of patients achieving platelet count >= lower limit of normal (LLN)."}
• {"endpoint_text":"- 12. Proportion of patients with normalization of LDH","definition_or_measurement_approach":"Proportion of patients with LDH values normalized versus baseline by Week 25."}
• {"endpoint_text":"- 13. Proportion of patients with >=25% decrease in serum creatinine from baseline","definition_or_measurement_approach":"Proportion of patients achieving ≥25% reduction in serum creatinine from baseline."}
• {"endpoint_text":"- 14. Time to complete TMA response (cTMAr)","definition_or_measurement_approach":"Time (e.g., days/weeks) from baseline to attainment of cTMAr."}
• {"endpoint_text":"- 15. Duration of cTMAr, among patients who achieved cTMAr","definition_or_measurement_approach":"Duration (time) that cTMAr is maintained among responders."}
• {"endpoint_text":"- 16. Proportion of patients with cTMAr","definition_or_measurement_approach":"Proportion of patients achieving cTMAr at specified timepoints."}
• {"endpoint_text":"- 17. Proportion of patients with maintained TMA control (mTMAc) from baseline through Week 25","definition_or_measurement_approach":"Proportion of patients with maintained TMA control from baseline through Week 25."}
• {"endpoint_text":"- 18. Incidence and severity of clinical manifestations of drug-target-drug complexes (DTDCs) in patients who switched to crovalimab treatment from either eculizumab or ravulizumab treatment","definition_or_measurement_approach":"Incidence and severity of clinical manifestations attributable to DTDCs in switch patients."}

Belgium

Latest Decision Or Authorization Date

19-11-2024

Number Of Sites

3

Number Of Participants

2

France

Latest Decision Or Authorization Date

20-11-2024

Number Of Sites

4

Number Of Participants

2

Hungary

Latest Decision Or Authorization Date

25-11-2024

Number Of Sites

1

Number Of Participants

1

Italy

Latest Decision Or Authorization Date

25-11-2024

Number Of Sites

1

Number Of Participants

1

Spain

Latest Decision Or Authorization Date

20-11-2024

Number Of Sites

2

Number Of Participants

1

Poland

Latest Decision Or Authorization Date

24-11-2024

Number Of Sites

4

Number Of Participants

2

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

Global CRO

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fulgent Genetics Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Cmic Pharma Science Co. Ltd.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Secugen S.L.","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Other third party duty","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Specialty Laboratory","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Teckro Limited","duties_or_roles":"Medical Communication","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}