A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises

Phase 3

Terminated

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

Interventions: Drug: Placebo
Drug: Inclacumab

Registration Number: NCT04927247

Lead Sponsor: Pfizer

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 72

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:
1. A hospital admission, or
2. An admission to an emergency room, observation unit, or infusion center for ≥ 12 hours, or
3. 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:
1. Has no medically determined cause other than a vaso-occlusive event, and
2. 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
3. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Placebo administered IV
inclacumab 30 mg/kg	Inclacumab	Inclacumab 30 mg/kg administered intravenously (IV)

Primary Outcome Measures

Name	Time	Method
Percentage 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	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])	A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. An admission for a VOC included 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. An acute episode of pain with no other cause other than a vaso-occlusive event included: uncomplicated VOC, acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.

Secondary Outcome Measures

Name	Time	Method
Time to First VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 90 Days of Randomization	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91]) or censored day, whichever occurred earlier	A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days was defined as the time between randomization date and onset date of first VOC event. For participants who did not experience a protocol-defined VOC within 90 days of randomization, time to first VOC was censored at the end of their time at risk (participant's end of study date or Study Day 91, whichever was earlier). An admission for a VOC included 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. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD. Kaplan-Meier method used for analysis.
Percentage 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	Within 30 days of randomization (randomization happened on Day 1 [Day 1 to Day 31])	A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. An admission for a VOC included 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. An acute episode of pain with no other cause other than a vaso-occlusive event included: uncomplicated VOC, acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.
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	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])	VOC leading to a healthcare visit was defined as VOC at (hospital, emergency room, clinic visit, or remote contact with a healthcare provider) that required parenteral pain medication (e.g., parenteral narcotic agents or parenteral nonsteroidal anti-inflammatory drugs \[NSAIDs\]), or an increased treatment with oral narcotics. Complicated VOCs included acute chest syndrome (ACS),hepatic sequestration, splenic sequestration, and priapism. For each participant, the time period at risk for evaluation of VOCs was from date of randomization to the participant's end of study date or study Day 91, whichever was earlier. In this outcome measure adjusted rates of VOCs (percentages) reported were based on estimate from a negative binomial model with the independent variable of treatment group (inclacumab, placebo) and adjusted for baseline hydroxyurea use (yes, no). All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.

Trial Locations

Locations (59): Strada Patient Care Center
🇺🇸
Mobile, Alabama, United States
University of South Alabama Children's and Women's Hospital
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Mobile, Alabama, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸
Mobile, Alabama, United States
Phoenix Children's Hospital
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Phoenix, Arizona, United States
Arkansas Children's Hospital
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Little Rock, Arkansas, United States
UCSF Benioff Children's Hospital, Oakland
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Oakland, California, United States
Children's Hospital of Orange County
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Orange, California, United States
St. Joseph's Hospital
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Tampa, Florida, United States
University of Michigan Hospitals - Michigan Medicine
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Ann Arbor, Michigan, United States
Functional Fluidics, Inc.
🇺🇸
Detroit, Michigan, United States
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Strada Patient Care Center
🇺🇸Mobile, Alabama, United States