A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent 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 a single dose of inclacumab, a P-selectin inhibitor, for a vaso-occlusive crisis (VOC) after an index VOC in participants with sickle cell disease (SCD). Participants will be randomized to receive either inclacumab or placebo.

Detailed Description
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The study will include approximately 280 adult and adolescent participants (≥ 12 years of age) with SCD. Eligible participants will be administered inclacumab or placebo intravenous (IV) as a single dose. Participants that complete the study through Day 90 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 of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises

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

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 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 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. 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. 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 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 healthcare 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 Screening 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 Screening 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 Screening. 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>Inclacumab 30 mg/kg administered intravenously (IV) | 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>Placebo administered IV | 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 |
| --- | --- | --- |
| Re-admission for a VOC within 90 days of randomization | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first re-admission for a VOC | Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication | Within 90 days of randomization | 
| Readmission for a VOC within 30 days | 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 healthcare visits | Rate of VOCs leading to a healthcare visit that requires parenteral pain medication or an increase in treatment with oral narcotics | Within 90 days following randomization | 
| Incidence of treatment-emergent adverse events (TEAEs) |  | Through Day 91 | 

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