This study is tackling the management of acute uncomplicated vaso occlusive episodes (voe) in patients with sickle cell disease (SCD). This study will enroll approximately 30 patients (at approximately 10-15 sites globally), aged 12-55 years old and =40 kg, with sickle cell disease genotype of HbSS or HbSß0, presenting to the ER/ED or acute medical facility with an acute uncomplicated vaso-occulsive episodes. sickle cell disease
Conditions
Interventions
The investigational medicinal products (IMPs) for this study are crovalimab and placebo. Crovalimab will be supplied by the Sponsor as a solution for infusion (IV) from a single-use vial, which contai
Crovalimab will be supplied by the Sponsor as a solution for infusion (IV) from a single-use vial, which contains an extractable volume of 2 mL or 340 mg (nominal) crovalimab. For IV infusion, the cro
The placebo will be an aqueous, isotonic, and sterile solution with a similar pH value as the crovalimab drug product. It should be handled, stored, and used in the same manner as crovalimab. The plac
Placebo
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Age
12 Years to 55 Years
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria Screen Visit #1 (Initial Screen) ? Signed ICF or Assent Form (as determined by patient’s age and individual site and country standards) ? Age >= 12 to =40 kg ? Willingness and ability to comply with all study visits and procedures ? Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbS ß0 (SCD genotype of sickle cell beta zero thalassemia) ? Vaccination against N. meningitidis serotypes A, C, W, and Y prior to initiation of study treatment. Vaccination against serotypes A, C, W, and Y should have been received = 2 as measured with the NRS on a 0-10 scale ? Ability to receive the single dose of study treatment within 12 hours from initial evaluation in the ER/ED or acute medical facility for the VOE (i.e., first vital signs measurements or first evaluation by a medical professional, whichever is first) ? Adequate hepatic function, including ALT < 3 x ULN and no clinical signs or known laboratory/radiographic evidence that are consistent with cirrhosis ? Adequate renal function, defined as c
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Screen Visit #1 (Initial Screen) ? More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit (e.g., ER/ED, hospital, clinic, infusion center, day hospital, etc.), as determined by medical history or by patient recall ? History of hematopoietic stem cell transplant ? Known or suspected hereditary complement deficiency ? 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 ? Current or previous treatment with a complement inhibitor therapy (e.g., crovalimab, eculizumab, or ravulizumab) Screen Visit #2 (VOE Presentation Screen) ? All criteria from Screen Visit #1 must be reconfirmed at Screen Visit #2 ? pain related to the current VOE ongoing for > 48 hours prior to VOE presentation ? Major surgery and/or hospitalization for any reason within 30 days prior to VOE presentation ? Acute pain related to avascular necrosis (where the presenting pain is limited to the affected joint), hepatic or splenic sequestration, or priapism per investigator assessment ? Pain atypical of an acute uncomplicated VOE that is the primary cause for presentation to the ER/ED or acute medical facility (e.g., chronic pain, abdominal pain, headache), or other alternative cause or explanation for pain presentation (e.g., infection, surgical pain) per investigator assessment ? Presentation with a critical illness necessitating ICU or critical care admission ? Evidence of or suspicion of ACS, defined as: the presence of new segmental radiographic pulmonary infiltrate involving at least one complete lung segment that is consistent with alveolar consolidation but excluding atelectasis, and at least one of the following additional signs or symptoms: chest pain, temperature >= 38.5oC (101.3oF), respiratory symptoms, or exam findings consistent with ACS ? Evidence or high suspicion of a severe systemic infection (e.g., osteomyelitis, pneumonia, meningitis, or sepsis) per investigator assessment - Patients with uncomplicated infections (e.g., uncomplicated urinary tract infections, uncomplicated acute otitis media, streptococcal pharyngitis, minor viral infections) may be included as per investigator assessment ? Presence of fever >= 38oC (100.oF) ? Infection requiring hospitalization or treatment with IV antibiotics within the prior 28 days, or oral antibiotics within the prior 14 days of VOE presentation – Patients on prophylactic antibiotics may be included ? History of N. meningitidis infection within 6 months prior to VOE presentation ? Known HIV infection with a documented CD4 count <200 cells/µL within 24 weeks prior to VOE presentation ? Transfusion or receipt of blood products within 3 months prior to VOE presentation or as part of BSC regimen for the current VOE, or current participation in a chronic transfusion protocol ? Immunized with a live attenuated vaccine within 30 days prior to VOE presentation ? Pregnant or breastfeeding, or intending to become pregnant during the study or within 322 days (approximately 10.5 months) after the study drug administration – Women of childbearing potential must have a documented negative pregnancy test result (urine or serum). If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy test ?
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: The safety objective for this study is to evaluate the safety of crovalimab compared with placebo ;Timepoints: end of study ;Measure: Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) ? Change from baseline in targeted vital signs and clinical laboratory test results ? Incidence and severity of infusion-related reactions and hypersensitivity ;Name: The PK objective for this study is to characterize the crovalimab PK profile;Timepoints: end of study ;Measure: Serum concentrations of crovalimab over time ? Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab (patients randomized to crovalimab);Name: The PD objective for this study is to evaluate PD biomarkers that can provide evidence of crovalimab activity;Timepoints: end of study ;Measure: Change over time in PD biomarkers, including total complement activity (CH50) measured by a LIA, total and free complement component 5 (C5) concentration, and sC5b-9 concentration;Name: The efficacy objective for this study is to characterize the efficacy of crovalimab compared with placebo;Timepoints: end of study ;Measure: ? Time to improvement of the primary acute uncomplicated VOE (for definition, see Section 2.4.1) from baseline, defined as the first achieved from the following criteria: – Confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two pain assessments conducted a minimum of 6 hours apart from each other (as measured with the Numerical Rating Scale [NRS] on a 0?10 scale) AND transition to oral pain medications for a minimum of 6 hours after the completion of the last dose of parenteral opioids, OR – Readiness for hospital discharge (as defined by the patient’s assessment that pain can be managed at home AND agreement from investigator), OR – Hospital discharge ? | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: The immunogenicity objective for this study is to evaluate the immune response to crovalimab;Timepoints: End of study ;Measure: Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study (patients randomized to crovalimab) ? Potential effects of ADAs on efficacy, safety, or PK endpoints;Name: The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that are predictive of response to crovalimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to crovalimab, are associated with susceptibility to developing adverse events or can lead to improved adverse event monitoring or investigation (i.e., safety biomarkers), or can increase the knowledge and understanding of disease biology and drug safety,;Timepoints: End of study ;Measure: ? Observed value and change over time in exploratory biomarkers including but not limited to markers of hemolysis, immune cell activation, inflammation, endothelial/vascular damage, and end-organ injury ? Relationship between biomarkers in blood and efficacy, safety, pharmacokinetics, immunogenicity, or other biomarker endpoints | — |
Countries
Brazil, France, Italy, Kenya, Lebanon, Netherlands, South Africa, Spain, United Kingdom, United States of America
Contacts
Public ContactAdlette Inati
Hematologist at NINI Hospital
Outcome results
None listed