A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises

Study Overview
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Brief Summary
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This Phase 3 study will assess the safety and efficacy of inclacumab, a P-selectin inhibitor, in reducing the frequency of vaso-occlusive crises (VOCs) in approximately 240 adult and adolescent participants (≥ 12 years of age) with sickle cell disease (SCD). Participants will be randomized to receive inclacumab or placebo.

Detailed Description
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Eligible participants will be administered inclacumab or placebo intravenous (IV) every 12 weeks. The total duration of treatment for each participant will be 48 weeks. Participants that complete the study through Week 48 will be provided the opportunity to enroll in an open-label extension (OLE) study.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises

Conditions
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Sickle Cell Disease, Vaso-occlusive Pain Episode in Sickle Cell Disease, Vaso-occlusive Crisis

Intervention / Treatment
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* Drug: Inclacumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has a confirmed diagnosis of SCD (HbSS, HbSC, HbSB0 thalassemia, or HbSB+ 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. Participant is male or female, ≥ 12 years of age at the time of informed consent. 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. Participants receiving erythropoiesis-stimulating agents (ESA, e.g., 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. Participants receiving hydroxyurea (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. Exclusion Criteria: Participant is receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion). Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to the Screening Visit Participant weighs > 133 kg (292 lbs.). Other protocol-defined Inclusion/Exclusion may apply.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: inclacumab, 30 mg/kg<br>Participants will receive inclacumab 30 mg/kg administered IV every 12 weeks | Drug: Inclacumab<br>* Inclacumab will be supplied in single use 10 mL vials at a concentration of 50 mg/mL. One vial contains 500 mg of inclacumab. This is a liquid concentrate for IV infusion.<br>|
| Placebo Comparator: placebo<br>Participants will receive placebo administered IV every 12 weeks. | Drug: Placebo<br>* Placebo will be supplied in single use 10 mL vials containing the same ingredients without the active drug. Placebo will be prepared as a liquid concentrate for IV infusion and administered in the same manner as active study drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of VOCs during the 48-week treatment period. | A 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 (hospitalization, 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 non-steroidal anti-inflammatoroy drugs (NSAIDS), or an increase in treatment with oral narcotics. Complicated VOCs of acute chest syndrome (ACS), hepatic sequestration, splenic sequestration, and priapism that meet the requirements listed above will be included in the primary endpoint | Day 1- Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first VOC during the 48-week treatment period. |  | Day 1- Week 48 | 
| Time to second VOC during the 48-week treatment period Efficacy. |  | Day 1- Week 48 | 
| Proportion of participants with no VOCs during the 48-week treatment period. |  | Day 1- Week 48 | 
| Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment period. | Admission 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. | Day 1- Week 48 | 
| Number of days of inpatient hospitalization for a VOC during the 48-week treatment period. |  | Day 1- Week 48 | 
| Incidence of treatment-emergent adverse events (TEAEs). |  | Day 1- Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemoglobin, blood disorders, red blood cells, sickle-like shape, mutation in hemoglobin gene, sickle-cell trait, sickle-cell crisis, Sickle Cell Disease, SCD, Vaso-occlusive Crises, VOC, SCA, RBCs