Patients with a diagnosis of sickle cell disease who have experienced between 2 and 10 vaso-occlusive crises in the 12 months preceding enrollment in this study. SCD, vaso-occlusive crisis, blood disorders, hemoglobin, red blood cells, sickle-like shape, mutation in hemoglobin gene, sickle-cell trait, sickle-cell crisis, Sickle Cell Disease SCD, Hydroxyurea/ Hydroxycarbamide Therapy, SCA
Conditions
Interventions
This study will assess the safety and efficacy of inclacumab in reducing the frequency of VOCs in approximately 240 adult and adolescent participants (= 12 years of age) with SCD. Initial enrollment
or
- Placebo administered IV Q12W.
At the time of randomization, participants will be stratified by Baseline hydroxyurea (HU) use (yes
no), number of VOCs (2 to 4
5 to 10) in the preceding 12 months, and geographic region (North America
sub-Saharan Africa
Europe/rest of world).
The total duration of treatment for each participant will be 48 weeks. Doses will be administered at Day 1 and Weeks 12, 24, and 36 with blood levels expected to be in the ta
Eligible participants will be randomized with a 1:1 ratio into one of two treatment arms as follows: Inclacumab 30 mg/kg administered IV every 12 weeks (Day 1, Week 12, Week 24, and Week 36)
or Placebo administered IV every 12 weeks (Day 1, Week
Treatment
Sponsors
Global Blood Therapeutics, Inc.
Eligibility
Sex/Gender
All
Age
12 Years to 90 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Participant has a confirmed diagnosis of SCD (HbSS, HbSC, HbSß0 thalassemia, or HbSß+ thalassemia genotype). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening. 2. Participant is male or female, = 12 years of age at the time of informed consent. NOTE: Initial study enrollment will include participants = 16 years of age until the DMC determines that adequate safety and PK data support the enrollment of participants 12 to 15 years of age. Sites will be informed by the Sponsor when participants 12 to 15 years of age may be enrolled. 3. Participant has experienced between 2 and 10 VOCs within the 12 months prior to the Screening Visit as determined by documented medical history. A prior VOC is defined as an acute episode of pain which: - Has no medically determined cause other than a vaso-occlusive event, and - Results in a visit to a medical facility (hospital, emergency department, urgent care center, outpatient clinic, or infusion center) or results in a remote contact with a healthcare provider; and - Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. 4. Participants receiving erythropoiesis-stimulating agents (ESA, erythropoietin [EPO]) must be on a stable dose for at least 90 days prior to the Screening Visit and expected to continue with the stabilized regimen throughout the course of the study. 5. Participants receiving HU, L-glutamine, or voxelotor (Oxbryta) must be on a stable dose for at least 30 days prior to the Screening Visit and expected to continue with the stabilized regimen throughout the course of the study. 6. Participant has adequate venous access, in the opinion of the Investigator, to comply with study procedures. 7. Participant understands the study procedures and agrees to participate in the study by giving written informed consent or parental permission/written assent. 8. 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: Exclusion Criteria Candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening or Baseline visits or at the timepoint specified in the individual criterion listed. 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 the Screening Visit. 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 during Screening. 7. Participant has a history of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including severe or unstable pulmonary hypertension. 8. Participant has had treatment for a malignancy within the 12 months prior to the Screening Visit (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 an 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 in another investigational trial within 30 days or 5 half-lives of the investigational agent (whichever is greater) prior to the Screening Visit. 13. 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 48-week treatment period. 15. Participant, parent, or legal guardian are unlikely to comply with the study procedures. 16. Participant has other medical, psychological, or addictive condition 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 caretaker unable/unlikely to comply with the study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Rate of VOCs.;Timepoints: the rate of VOCs during the 48-week treatment period will be compared between the inclacumab and placebo arms with the use of negative binomial regression model. ;Measure: The incidence of VOC events will be collected every 4 weeks. Each month on non-treatment visit days, participants will be contacted by phone to determine if a VOC event or a pain crisis leading to contact with a healthcare provider without a visit to a medical facility has occurred, to collect AEs, and to record changes to concomitant medications. A VOC is defined as an acute episode of pain that: 1) Has no medically determined cause other than a vaso-occlusive event, and 2) Results in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or results in a remote contact with a healthcare provider; and 3) Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics.;Name: Change in Laboratory assessments.;Timepoints: at each visit ;Measure: Complete blood count, chemistry and coagulation | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Time to first VOC during the 48-week treatment period. ;Timepoints: 48-week treatment period;Measure: The secondary efficacy endpoints are based on collection of the incidence and timing of VOCs (per the definition in the primary endpoint) after randomization, QOL assessments and on hospital durations. ;Name: Time to second VOC during the 48-week treatment period.;Timepoints: 48-week treatment period;Measure: The secondary efficacy endpoints are based on collection of the incidence and timing of VOCs (per the definition in the primary endpoint) after randomization, QOL assessments and on hospital durations. ;Name: Proportion of participants with no VOCs during the 48-week treatment period. ;Timepoints: 48-week treatment period;Measure: The secondary efficacy endpoints are based on collection of the incidence and timing of VOCs (per the definition in the primary endpoint) after randomization, QOL assessments and on hospital durations. ;Name: Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment.;Timepoints: 48-week treatment period;Measure: The secondary efficacy endpoints are based on collection of the incidence and timing of VOCs (per the definition in the primary endpoint) after randomization, QOL assessments and on hospital durations. ;Name: Number of days of inpatient hospitalization for a VOC during the 48-week treatment period. ;Timepoints: 48-week treatment period;Measure: The secondary efficacy endpoints are based on collection of the incidence and timing of VOCs (per the definition in the primary endpoint) after randomization, QOL assessments and on hospital durations. ;Name: Incidence of treatment-emergent adverse events.;Timepoints: At each visit ;Measure: Treatment-emergent adverse events (TEAEs). | — |
Countries
Lebanon
Contacts
Public ContactAziz Zoghbi
Director of Country Oversight and Management MENA, Gulf and Africa
Outcome results
None listed