A Randomized, Double-blind, Placebo-controlled, Multicenter Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises
- Conditions
- Patients with a diagnosis of sicke cell disease who have experienced between 2 and 10 vaso-occlusive crises in the 12 months preceding enrollment and have been hospitalized for an index vaso-occlusive crises.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
- Registration Number
- LBCTR2021074831
- Lead Sponsor
- Global Blood Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 280
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.
NOTE: Initial study enrollment will include only participants = 16 years of age until the DMC recommends to the Sponsor 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.
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).
5. Participant has experienced between 2 and 10 VOCs (inclusive) 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:
• 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.
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 tests 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 ooph
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 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.
NOTE: Laboratory assessments conducted during Screening may be done by the local laboratory and must include at least a CBC with total and differential leukocyte count, platelet count, and hemoglobin, a chemistry panel with creatinine, and a serum pregnancy test to assess participant eligibility. Laboratory assessments conducted during the index VOC admission that are obtained within 7 days prior to screening may be used for Screening assessments if done as part of standard medical care.
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.
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 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 caretaker unable/unlikely to comply with the study procedures.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ame: Index VOC requiring admission;Timepoints: 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;Measure: 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;Name: Change in Laboratory assessments;Timepoints: at each visit ;Measure: Complete blood count, chemistry and coagulation
- Secondary Outcome Measures
Name Time Method