Haematological Disorders Sickle Cell Disease
Conditions
Interventions
Placebo
Sponsors
Global Blood Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant has an index VOC. The index VOC is any VOC that required admission to a healthcare facility and treatment with parenteral pain medication. An admission for the index VOC includes: a. A hospital admission, or b. An admission to an emergency room, observation unit, or infusion center for = 12 hours, or c. 2 visits to an emergency room, observation unit, or infusion center over a 72 hour period. for an acute episode of pain with no other cause other than a vaso-occlusive event that includes the following: - Uncomplicated VOC, - Acute chest syndrome (ACS), - Acute hepatic sequestration, - Acute splenic sequestration, or - Priapism. 2. Participant has a confirmed diagnosis of SCD any genotype). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing at Baseline. 3. Participant is male or female, = 12 years of age at the time of informed consent. 4. Participant is able to complete screening and receive study drug within 5 days following investigator-assessed resolution of index VOC (for example, hospital discharge, discontinuation of parenteral pain medication, or transition to oral pain medication). Participant has experienced between 2 and 10 VOCs within the 12 months prior to Screening as determined by documented medical history. The index VOC is not to be considered as one of the 2 to 10 events. A prior VOC is defined as an acute episode of pain that: a. Has no medically determined cause other than a vaso-occlusive event, and b. Results in a visit to a healthcare facility (hospital, emergency department, urgent care center, outpatient clinic, or infusion center) or results in a remote contact with a healthcare provider; and c. Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. 6. Participants receiving erythropoiesis-stimulating agents (ESA, eg, erythropoietin [EPO]) must be on a stable dose for at least 90 days prior to Screening and expected to continue with the stabilized regimen throughout the course of the study. 7. Participants receiving HU, L-glutamine, or voxelotor must be on a stable dose for at least 30 days prior to Screening and expected to continue with the stabilized regimen throughout the course of the study. 8. Participant has adequate venous access, in the opinion of the Investigator, to comply with study procedures. 9. Participant understands the study procedures and agrees to participate in the study by giving written informed consent or parental permission/written assent. 10. Women of childbearing potential (WOCBP) are required to have a negative serum pregnancy test at the Screening Visit and negative urine pregnancy test on all subsequent clinic visits and must agree to use a highly effective method of contraception throughout the study period and for at least 165 days after dosing. Female participants will not be considered of childbearing potential if they are pre-menarchal, surgically sterile (hysterectomy, bilateral salpingectomy, tubal ligation, or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause, confirmed by follicle-stimulating hormone test results).
Exclusion criteria
Exclusion criteria: 1. Participant is receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion). 2. Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to Screening. 3. Participant weighs > 133 kg (292 lbs.). 4. Participant has a significant active and poorly controlled (unstable) hepatic disorder clearly unrelated to SCD. 5. Participant has any of the following laboratory values at Screening: a. Absolute neutrophil count (ANC) < 1.0 × 109/L b. Platelet count < 80 × 109/L c. Hemoglobin < 4.0 g/dL for adults and < 5.0 g/dL for participants ages 12 to < 18 years of age d. Estimated glomerular filtration rate (eGFR) < 30 mL/min using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula in adults, and Schwartz formula in adolescents. 6. Participant has known active (symptomatic) COVID infection or tests positive for COVID-19 at any time during their index admission. 7. Participant has a history of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to Screening including severe or unstable pulmonary hypertension. 8. Participant has had treatment for a malignancy within the 12 months prior to Screening (except non-melanoma skin cancer and in situ cervical cancers). 9. Participant has had a stroke within the 2 years prior to the Screening Visit. 10. Participant has a positive test indicative of active malaria infection at Screening. Testing to be conducted at local laboratories in malaria-endemic regions at the discretion of the Investigator. 11. Participant has any confirmed clinically significant drug allergy and/or known hypersensitivity to monoclonal antibody therapeutics or formulation components of the study drug or a related drug. 12. Participant has been treated with another investigational agent within 30 days or 5 half lives of the investigational agent (whichever is greater) prior to Screening. Participant has had a major surgery within 8 weeks prior to the Screening Visit. 14. Participant is pregnant, breastfeeding, or planning to become pregnant during the 90-day treatment period. 15. Participant, parent, or legal guardian are unlikely to comply with the study procedures. 16. Participant has other medical, or psychological, or behavioral conditions that, in the opinion of the Investigator, would: confound or interfere with evaluation of safety, efficacy, and/or PK of the investigational drug; prevent compliance with the study protocol; preclude informed consent; or,render the participant, parent, or legal guardian unable/unlikely to comply with the study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint for this study is, following an index VOC, the proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days of randomization. An admission for a VOC includes: •A hospital admission, or •An admission to an emergency room, observation unit, or infusion center for = 12 hours, or •2 visits to an emergency room, observation unit, or infusion center over a 72 hour period. for an acute episode of pain with no other cause other than a vaso-occlusive event that includes the following: •Uncomplicated VOC, •Acute chest syndrome (ACS), •Acute hepatic sequestration, •Acute splenic sequestration, or •Priapism. The definition of the index VOC requiring admission is the same as the primary endpoint VOC requiring admission. To ensure consistency across study sites, all on-study VOCs reported by the study investigators will be adjudicated by an independent, blinded panel comprised of experts in SCD. The primary efficacy analysis will be performed on adjudicated data. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy endpoints of the study are the following: • Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days of randomization. • Proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 30 days of randomization. • Rate of VOCs leading to a healthcare visit (hospital, emergency room, clinic visit, or remote contact with a healthcare provider) that requires parenteral pain medication (eg, parenteral narcotic agents or parenteral nonsteroidal anti-inflammatory drugs [NSAIDs]), or an increase in treatment with oral narcotics within 90 days following randomization. | — |
Countries
Brazil, Colombia, Egypt, France, Germany, Ghana, Italy, Kenya, Lebanon, Nigeria, Oman, Turkey, United Kingdom, United States of America, Zambia
Contacts
Public ContactMargot Hottmann
Senior Clinical Trial Manager
Outcome results
None listed