What is the mechanism of action of this treatment?

P-selectin inhibitors, such as inclacumab and crizanlizumab, work by blocking the P-selectin protein on the surface of endothelial cells and platelets, which reduces the adhesion of sickled red blood cells and leukocytes to the vascular endothelium. This helps to prevent vaso-occlusive crises (VOCs), a common and painful complication of SCD. Hydroxyurea, another common treatment, increases the production of fetal hemoglobin (Hb F), which reduces the sickling of red blood cells and decreases the frequency of VOCs. These treatments are crucial for SCD patients as they help to manage pain, reduce hospitalizations, and improve overall quality of life by targeting the underlying mechanisms of the disease.

What side effects are associated with this type of intervention?

Hydroxyurea, a common treatment for Sickle Cell Disease, can cause side effects such as bone marrow suppression, leading to decreased white blood cells and platelets, gastrointestinal disturbances, and potential long-term risks like leukemia. Chronic transfusions may result in iron overload, alloimmunization, and transfusion reactions. Investigational therapies like P-selectin inhibitors, including inclacumab, are being studied for their safety profile, but potential side effects could include infusion reactions and increased risk of infections.

What prior FDA approvals exist?

Hydroxyurea is a well-established FDA-approved treatment for Sickle Cell Disease, known for its efficacy in reducing vaso-occlusive crises and other complications. It is recommended as the first-line therapy for individuals with SCD. While inclacumab, a P-selectin inhibitor, is currently under investigation, it represents a newer class of treatments aimed at reducing VOCs by targeting the pathogenesis of SCD-associated vaso-occlusion. Other treatments include chronic transfusions and hematopoietic stem cell transplantation, which are used in specific cases but are not as broadly applicable as hydroxyurea.

What other types of research exist?

Promising novel alternatives to Inclacumab for Sickle Cell Disease patients include Crizanlizumab, an adhesion inhibitor of sickled red blood cells, and Sevuparin, a heparin-derived polysaccharide with anti-adhesive properties. Both have shown efficacy in reducing the frequency of vaso-occlusive crises.

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P-selectin inhibitor

Inclacumab for Sickle Cell Crisis

Phase 3

Waitlist Available

Research Sponsored by Global Blood Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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.

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1- week 48

Awards & highlights

Pivotal Trial

Summary

This trial tests inclacumab in individuals with sickle cell disease. It aims to reduce painful episodes.

Who is the study for?

This trial is for males and females aged 12 or older with sickle cell disease who've had 2-10 pain crises in the past year. They must be on a stable dose of certain medications like hydroxyurea, L-glutamine, or voxelotor for at least 30 days. Those on regular blood transfusions, recent crizanlizumab users, or weighing over 133 kg cannot participate.

What is being tested?

The study tests inclacumab against a placebo to see if it can reduce painful episodes known as vaso-occlusive crises in people with sickle cell disease. About 240 participants will either receive inclacumab or a placebo randomly.

What are the potential side effects?

While specific side effects are not listed here, inclacumab could potentially cause reactions related to the immune system since it targets P-selectin involved in inflammation and blood cells sticking together.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've had 2-10 severe pain episodes related to my condition in the last year, requiring medical attention.

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I have had 2 to 10 episodes of severe pain in the last year.

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I need strong pain medication given through injections or an increase in my oral pain medication.

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I have been on a stable dose of ESA for at least 90 days and will continue it during the study.

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I have been diagnosed with sickle cell disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I regularly receive blood transfusions.

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I have taken ADAKVEO® within the last 90 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1- week 48

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1- week 48

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1- week 48 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Rate of VOCs during the 48-week treatment period.

Secondary study objectives

Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment period.

Other study objectives

PD parameter (P-selectin inhibition)

PD parameter (Platelet Leukocyte Aggregation)

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: inclacumab, 30 mg/kgExperimental Treatment1 Intervention

Participants will receive inclacumab 30 mg/kg administered IV every 12 weeks

Group II: placeboPlacebo Group1 Intervention

Participants will receive placebo administered IV every 12 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Inclacumab

2021

Completed Phase 3

~250

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

P-selectin inhibitors, such as inclacumab and crizanlizumab, work by blocking the P-selectin protein on the surface of endothelial cells and platelets, which reduces the adhesion of sickled red blood cells and leukocytes to the vascular endothelium. This helps to prevent vaso-occlusive crises (VOCs), a common and painful complication of SCD. Hydroxyurea, another common treatment, increases the production of fetal hemoglobin (Hb F), which reduces the sickling of red blood cells and decreases the frequency of VOCs. These treatments are crucial for SCD patients as they help to manage pain, reduce hospitalizations, and improve overall quality of life by targeting the underlying mechanisms of the disease.

A critical evaluation of crizanlizumab for the treatment of sickle cell disease.