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

• ClinicalTrials.gov Identifier: NCT04927247
• Recruitment Status: Recruiting
• First Posted: June 15, 2021
• Last Update Posted: March 15, 2022
• Sponsor: Global Blood Therapeutics
• Information provided by (Responsible Party): Global Blood Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sickle Cell Disease; Vaso-occlusive Crisis; Vaso-occlusive Pain Episode in Sickle Cell Disease	Drug: Inclacumab; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind study
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 13, 2021
• Estimated Primary Completion Date: December 11, 2023
• Estimated Study Completion Date: March 11, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: inclacumab 30 mg/kg; Inclacumab 30 mg/kg administered intravenously (IV)	Drug: Inclacumab; 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.
Placebo Comparator: placebo; Placebo administered IV	Drug: Placebo; 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.

Outcome Measures

Primary Outcome Measures :

1. Re-admission for a VOC within 90 days of randomization [ Time Frame: 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

Secondary Outcome Measures :

1. Time to first re-admission for a VOC [ Time Frame: Within 90 days of randomization ]
   Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication
2. Readmission for a VOC within 30 days [ Time Frame: Within 30 days of randomization ]
   Proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication
3. Rate of VOCs leading to healthcare visits [ Time Frame: Within 90 days following randomization ]
   Rate of VOCs leading to a healthcare visit that requires parenteral pain medication or an increase in treatment with oral narcotics
4. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through Day 91 ]

Other Outcome Measures:

1. PD parameter (P-selectin inhibition) [ Time Frame: Through Day 91 ]
   To characterize the pharmacodynamics (PD) (P-selectin inhibition) of inclacumab at 30 mg/kg
2. PD parameter (Platelet Leukocyte Aggregation) [ Time Frame: Through Day 91 ]
   To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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.
2. 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.
3. Participant is male or female, ≥ 12 years of age at the time of informed consent.

4. 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.
5. 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.
6. 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:

1. Participant is receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion).
2. Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to Screening.
3. Participant weighs > 133 kg (292 lbs.).

Other protocol-defined Inclusion/Exclusion may apply.

Contacts and Locations

Contacts

Contact: Carolyn Hoppe, MD; 650-822-8728; choppe@gbt.com

Contact: Deanna Franklin; dfranklin@gbt.com

Locations

United States, Alabama

University of South Alabama Children's and Women's Hospital; Not yet recruiting

Mobile, Alabama, United States, 36604

Contact: Jennifer Williams 251-405-5115 jgwilliams@health.southalabama.edu

Principal Investigator: Preethi Marri, MD

United States, Arkansas

Arkansas Children's Hospital; Recruiting

Little Rock, Arkansas, United States, 72202

Contact: Carol D'Ann Pierce, RN 501-364-4440 piercecarold@uams.edu

Principal Investigator: Carolyn Suzanne Saccente, MD

United States, Georgia

Children's Healthcare of Atlanta at Scottish Rite Hospital; Not yet recruiting

Atlanta, Georgia, United States, 30342

Contact: Amanda Sanders 404-785-0305 amanda.sanders2@choa.org

Principal Investigator: Robert C Brown, MD

United States, Illinois

University of Illinois at Chicago; Not yet recruiting

Chicago, Illinois, United States, 60607

Contact: Taif Hassan 312-996-9052 tohassan@uic.edu

Principal Investigator: Santosh Saraf, MD

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Bre'Anna Simpson 734-615-4630 sbreanna@med.umich.edu

Principal Investigator: Ghada Abusin, MD

United States, New York

Jacobi Medical Center; Recruiting

Bronx, New York, United States, 10461

Contact: Sabahete Zegiraj 718-918-6973 zeqirajs@nychhc.org

Principal Investigator: Kenneth Rivlin, MD

United States, North Carolina

Duke University Medical Center; Not yet recruiting

Durham, North Carolina, United States, 27710

Contact: Lindsey Muller, MSc 919-684-3543 lindsey.muller@duke.edu

Principal Investigator: Marilyn Telen, MD

United States, Tennessee

St Jude Children's Research Hospital; Not yet recruiting

Memphis, Tennessee, United States, 38105

Contact: Gail Fortner gail.fortner@stjude.org

Principal Investigator: Jeremie Estepp, MD

Lebanon

Nini Hospital; Recruiting

Tripoli, Lebanon

Contact: Kamleh Ibrahim 96170500375 kamleh.ibrahim@hopitalnini.com

Principal Investigator: Adlette Inati, MD

Sponsors and Collaborators

Global Blood Therapeutics

More Information

Additional Information:

Global Blood Therapeutics (GBT) website 

• Responsible Party: Global Blood Therapeutics
• ClinicalTrials.gov Identifier: NCT04927247
• Other Study ID Numbers: GBT2104-132; 2020-005287-60 ( EudraCT Number )
• First Posted: June 15, 2021
• Last Update Posted: March 15, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Global Blood Therapeutics:

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; SCD; Vaso-occlusive Crisis; VOC; SCA

Additional relevant MeSH terms:

Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn