patients with SCD (HbSS and HbSb0) aged 12-55 years with 2-10 documented VOEs in the 12 months prior to randomization. This exploratory study aims to target a homogenous population related to age and SCD genotype, to minimize interpatient variability and facilitate the interpretation of endpoints. sickle cell disease
Conditions
Interventions
The investigational medicinal products (IMPs) for this study are crovalimab and placebo.
Crovalimab vials will be supplied by the Sponsor as a solution for IV infusion/SC injection from a single-use v
Crovalimab is a novel, humanized anti-complement component 5 (C5) monoclonal antibody. Crovalimab binds to C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the gene
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Age
12 Years to 55 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria Patients must meet the following criteria for study entry: ? Signed Informed Consent Form (ICF) ? Signed Assent Form when appropriate, as determined by patient’s age and individual site and country standards ? Age 12 to 55 years at time of signing ICF or Assent Form ? Body weight = 40 kg at screening ? Willingness and ability to comply with the study protocol including scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of the HVQ and PRO questionnaires through the use of an electronic device ? Male or female with confirmed diagnosis of sickle cell anemia (HbSS or HbSß0) ? Two or more (= 2) to =10 documented VOEs in the 12 months prior to randomization as determined by medical history (VOE should include the occurrence of typical symptoms, a visit to a specific medical facility and/or healthcare professional, and receipt of pain medication as defined for the medical facility VOE endpoint in ? If receiving concurrent SCD-directed therapy (e.g., hydroxyurea, L-glutamine, crizanlizumab, or voxelotor), the patient must have been on a stable dose, except for weight-based titration, with good adherence by the investigator’s assessment for a minimum of 3 months prior to study enrollment (Day 1). There should be no plans to modify the patients’ dosing throughout the study duration, other than for safety reasons. ? If receiving erythropoietin, the patient must have been prescribed this medication for the preceding 3 months and be dose-stabilized for at least 3 months prior to study enrollment (Day 1). ? Vaccinations: o Vaccination against N. meningitidis serotypes A, C, W, and Y prior to initiation of treatment. Vaccination against serotypes A, C, W, and Y should have been received < 3 years prior to initiation of study treatment, or must be up to date in accordance with the most current local guidelines or SOC, as applicable for patients with complement deficiency and SCD. If vaccination against serotypes A, C, W, and Y is not required per local SOC, the Advisory Committee on Immunization Practices (ACIP) 2020 guidelines should be used. Vaccination against serotype B should be administered in accordance with the most current local guidelines or SOC for patients with complement deficiency and SCD. Vaccination currency against serotypes A, C, W, Y, and B should be maintained throughout the study, including the safety follow-up, per local guidelines. o Vaccinations against H. influenza type B and S. pneumonia in accordance with most current SCD-specific guidelines or local SOC. If the vaccination(s) are not required per local guidelines, the ACIP guidelines should be used. Vaccination currency should be maintained throughout the study, including the safety follow-up, per local guidelines. o Note, if any of the above vaccinations are received < 2 weeks before initiating treatment, appropriate antibiotic prophylaxis per local standard of practice must be initiated. Antibiotic prophylaxis should be continued until 2 weeks after the vaccination is complete. ? Patients who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation ? Otherwise appropriate medical history and physical and laboratory evaluation that are acceptable for inclusion in this clinical trial ? Adequate hepatic function, with ALT < 3 xULN at the time of screenin
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: ? History of hematopoietic stem cell transplant ? Participating in a chronic transfusion program (preplanned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study. Episodic simple transfusion is permitted. ? History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment (crovalimab or placebo), including hypersensitivity to human, humanized, or murine monoclonal antibodies or known hypersensitivity to any constituent of the product ? Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial ? Concurrent disease, treatment, procedure, surgery, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the patient, or would, in the opinion of the investigator, preclude the patient’s safe participation in and completion of the study ? Hemoglobin 5 years prior to study drug administration (Day 1) are eligible. o Patients with curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix at any time prior to study drug administration (Day 1) are eligible. o 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 to study drug administration (Day 1) are eligible ? Known HIV infection with documented CD4 count <200 cells/µL within 24 weeks prior to screening ? History of N. meningitidis infection within the prior 6 months Kindly refer to the exclusion criteria p 46 on the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: The primary efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo;Timepoints: end of study ;Measure: Annualized rate of medical facility VOEs (AVR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: The secondary efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo;Timepoints: end of study ;Measure: Annualized rate of home VOE captured by patient report on a handheld device at home ? Annualized rate of uncomplicated medical facility VOE ? Annualized rate of ACS ? Annualized rate of days hospitalized for medical facility VOE ( ? Annualized rate of days hospitalized for treatment of non-VOE complications of SCD ? Change in hematologic measures from baseline to Week 49 ? Time to first medical facility VOE from randomization as defined in primary efficacy endpoint ? Change in urinary albumin-creatinine ratio from baseline to Week 49 ? Change from baseline to Week 49 in tricuspid regurgitant jet velocity (TRV) ? Proportion of patients with TRV ?2.5 m/s at Week 49 ? Change from baseline to Week 49 in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults;Name: The exploratory efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo;Timepoints: end of study ;Measure: Combined rate of VOEs leading to medical facility visit or treated only at home ? Annualized rate of home VOE captured by patient recall at study clinic visits ? Annualized number of RBC transfusions ? Endpoints collected during any medical facility VOE and requiring hospitalization between baseline visit and Week 49: o Re-admission rate for a subsequent medical facility VOE within 28 days of discharge o Duration in days of hospitalization for each medical facility VOE o Need for RBC transfusion during admission for each medical facility VOE ? Change from baseline to Week 49 in the scores of the following PROs: o Emotional impact and stiffness impact as assessed by the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) in adults Physical functioning as assessed by the PROMIS Physical Function in adults o Physical functioning as assessed by the Pediat | — |
Countries
Brazil, France, Italy, Netherlands, South Africa, Spain, Turkey, United Kingdom, United States of America
Contacts
Public ContactAdlette Inati
Hematolog ist at NINI Hospital
Outcome results
None listed