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

Phase 3

Completed

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Participants will receive placebo administered IV every 12 weeks.
inclacumab, 30 mg/kg	Inclacumab	Participants will receive inclacumab 30 mg/kg administered IV every 12 weeks

Primary Outcome Measures

Name	Time	Method
Rate of VOCs during the 48-week treatment period.	Day 1- Week 48	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

Secondary Outcome Measures

Name	Time	Method
Time to second VOC during the 48-week treatment period Efficacy.	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
Time to first VOC during the 48-week treatment period.	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.	Day 1- Week 48	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.

Locations (97): UCI Center for clinical research
🇺🇸
Orange, California, United States
University of South Alabama Children's and Women's Hospital
🇺🇸
Mobile, Alabama, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸
Mobile, Alabama, United States
University of South Alabama Strada Patient Care Center
🇺🇸
Mobile, Alabama, United States
Phoenix Children's Hospital
🇺🇸
Phoenix, Arizona, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
UCSF Benioff Children's Hospital, Oakland
🇺🇸
Oakland, California, United States
UC Irvine Health
🇺🇸
Orange, California, United States
Uconn Health/Uconn John Dempsey Hospital/Neag Comprehensive Cancer Center/New England Sickle Cell
🇺🇸
Farmington, Connecticut, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
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UCI Center for clinical research
🇺🇸Orange, California, United States