D593 Haemolytic-uraemic syndrome Haemolytic-uraemic syndrome
Conditions
Interventions
Study drug administration must be initiated within 4 weeks of the onset of the TMA episode in
the naive patients. All patients will receive crovalimab according to a weight-based tiered dosing approac
Sponsors
F. HOFFMANN-LA ROCHE LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed Informed Consent Form - Signed Assent Form when appropriate, as determined by patient's age and individual site and country standards - Age = 12 years at time of signing Informed Consent Form or Assent Form - Body weight = 40 kg at screening - Willingness and ability to comply with all study visits and procedures - Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first study drug administration. Vaccination currency should be maintained throughout the study in accordance with most current local guidelines or standard-of-care as applicable in patients with complement deficiency. - Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae, according to national vaccination recommendations (e.g., Advisory Committee on Immunization Practices guidelines). If not previously done, vaccination administered no later than one week after the first study drug administration. - For patients receiving other therapies (e.g., immunosuppressants, corticosteroids, mammalian target of rapamycin inhibitor [mTORi]; [i.e., sirolimus, everolimus] or calcineurin inhibitors [i.e., cyclosporine or tacrolimus]): stable dose for =28 days prior to screening and up to the first drug administration. - Adequate hepatic function, ALT = 3 x ULN at the time of screening; no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis - For female patients of childbearing potential, an agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception - Patients with a prior kidney transplant are eligible if they have: o Known history of complement-mediated aHUS prior to the kidney transplant For Naive Cohort only: - Evidence of TMA, as defined by a patient with all of the following laboratory findings at screening and up to the first drug administration: o Platelet count < LLN o LDH = 1.5 x ULN and hemoglobin = LLN for age and sex o Serum creatinine =ULN in adults, or = 97.5th percentile for age in adolescents (12-18 years). Patients who require dialysis for acute kidney injury are also eligible.
Exclusion criteria
Exclusion criteria: TMA associated with non-aHUS related renal disease • Positive direct Coombs test • Identified drug exposure-related TMA • History of organ transplant, other than kidney transplant • Chronic dialysis (defined as dialysis for more than 4 weeks since TMA presentation), and/or end stage renal disease • History of a kidney disease, other than aHUS, affecting renal function, such as: • Known kidney biopsy finding suggestive of underlying disease other than aHUS • Known kidney ultrasound finding consistent with an alternative diagnosis to aHUS • Known family history and/or genetic diagnosis of non-complement mediated genetic renal disease • History of Neisseria meningitidis infection within 6 months prior to screening and up to the first drug administration • Known or suspected immune deficiency (e.g., history of frequent recurrent infections) • Positive HIV test • Life expectancy of < 4 weeks • Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration • Presence of fever (=38 °C) within 7 days before the first drug administration Patient with active or evolving multi-system organ dysfunction or failure • Immunized with a live attenuated vaccine within 1 month before first drug administration • Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome • Patients receiving chronic IV immunoglobulin (IVIg) within 8 weeks prior to start of screening, unless for unrelated medical condition (e.g., hypogammaglobinemia) • History of malignancy within 5 years prior to screening and up to the first drug administration, with the following exceptions: - Patients with any malignancy treated with curative intent and the malignancy has been in remission without treatment for ?5 years prior the first drug administration are eligible. - Patients with curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix at any time prior to first drug administration, with no evidence of recurrence, are eligible. - Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior the first drug administration are eligible. - 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 - Female patients who are pregnant, breastfeeding, or have the intention of becoming pregnant during the study or within 6 months after the final dose of the study treatment. - Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug. - Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within five half-lives of that investigational product, whichever is greater. Patients enrolled in an eculizumab or ravulizumab interventional study are eligible for the Switch Cohort, provided they fulfill eligibility and stop their current trial. - Substance abuse within 12 months prior to screening, in the investigator's judgment - Splenectomy <6 months prior to screening - Use of tranexamic acid within 7 days prio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| cTMAr is defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (28 days) apart, and any measurement in between: - Platelet count = lower limit of normal (LLN), and - Normalization of LDH (i.e., = ULN), and - =25% decrease in serum creatinine from baseline NAME OF THE RESULT: Proportion of patients with complete TMA response (cTMAr) anytime from baseline to Week 25 (after 24 weeks on treatment) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from baseline to Week 25 | — |
Secondary
| Measure | Time frame |
|---|---|
| The effect of crovalimab in patients based on the following endpoints: For both Cohorts: 1.- Dialysis requirement status (yes/no) change from baseline to Week 25 (after 24 weeks on treatment); patients were considered as being on dialysis at baseline if dialysis occurred within 5 days prior to the first study drug administration 2.- Observed value and change from baseline in estimated glomerular filtration rate (eGFR), as per Appendix 9 3.- Proportion of patients with change from baseline in CKD stage, classified as improved, stable (no change), or worsened based on the National Kidney Foundation Chronic Kidney Disease Stage 4.- Observed value and change from baseline in hematologic parameters (platelet count, LDH, hemoglobin) 5.- In adults (?18 years), change from baseline in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire For Naive Cohort only: 1.- Proportion of patients with platelet count = LLN at two separate assessments, obtained at least 4 weeks (28 days) apart, by Week 25 (after 24 weeks of treatment) 2.- Proportion of patients with normalization of LDH (i.e., = ULN) at two separate assessments, obtained at least 4 weeks (28 days) apart, by Week 25 (after 24 weeks of treatment) 3.- Proportion of patients with = 25% decrease in serum creatinine from baseline, confirmed at two separate assessments obtained at least 4 weeks (28 days) apart, by Week 25 (after 24 weeks of treatment) 4.- Time to cTMAr 5.- Duration of cTMAr, among patients who achieved cTMAr 6.- Proportion of patients with cTMAr at Week 25. NAME OF THE RESULT: he effect of crovalimab in patients based on the following endpoints: For both Cohorts: 1.- Dialysis requirement status (yes/no) change from baseline to Week 25 2.- Glomerular filtration rate (eGFR) 3.- Change from baseline in chronic kidney disease (CKD) stage 4.- Hematologic parameters (platelet count, LDH, hemoglobin) 5. | — |
Countries
Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Peru, Poland, South Africa, Spain, Turkey, United States
Contacts
Public ContactLIZETH MABEL PEREZ
ROCHE FARMA (PERU) S.A.
Outcome results
None listed