TRIALS IN PROGRESS: THE THRIVE STUDIES EVALUATING THE EFFICACY, SAFETY, AND LONG-TERM TREATMENT WITH INCLACUMAB, A P-SELECTIN INHIBITOR, IN PATIENTS WITH SICKLE CELL DISEASE
Author(s): ,
Biree Andemariam
Affiliations:
New England Sickle Cell Institute, University of Connecticut Health,Farmington,États-unis;New England Sickle Cell Institute, University of Connecticut Health,Farmington,Vereinigte Staaten;New England Sickle Cell Institute, University of Connecticut Health,Farmington,Stati Uniti;New England Sickle Cell Institute, University of Connecticut Health,Farmington,United States;New England Sickle Cell Inst
,
Adlette Inati
Affiliations:
Lebanese American University, Byblos and Beirut, Nini Hospital,Tripoli,Liban;Lebanese American University, Byblos and Beirut, Nini Hospital,Tripoli,Libanon;Lebanese American University, Byblos and Beirut, Nini Hospital,Tripoli,Libano;Lebanese American University, Byblos and Beirut, Nini Hospital,Tripoli,Lebanon;Lebanese American University, Byblos and Beirut, Nini Hospital,Tripoli,Líbano;Lebanese
,
Rafaella Colombatti
Affiliations:
Clinic of Pediatric Hematology Oncology, Department of Woman's and Child's Health, Azienda Ospedale – Università di Padova,Padua,Italie;Clinic of Pediatric Hematology Oncology, Department of Woman's and Child's Health, Azienda Ospedale – Università di Padova,Padua,Italien;Clinic of Pediatric Hematology Oncology, Department of Woman's and Child's Health, Azienda Ospedale – Università di Padova,Padu
,
Caterina Minniti
Affiliations:
Albert Einstein College of Medicine,Bronx,États-unis;Albert Einstein College of Medicine,Bronx,Vereinigte Staaten;Albert Einstein College of Medicine,Bronx,Stati Uniti;Albert Einstein College of Medicine,Bronx,United States;Albert Einstein College of Medicine,Bronx,Estados Unidos;Albert Einstein College of Medicine,Bronx,Verenigde Staten;Albert Einstein College of Medicine,Bronx,Estados Unidos;Alb
,
Clark Brown
Affiliations:
Aflac Cancer and Blood Disorder Center of Children's Healthcare of Atlanta and Department of Pediatrics, Emory School of Medicine,Atlanta,États-unis;Aflac Cancer and Blood Disorder Center of Children's Healthcare of Atlanta and Department of Pediatrics, Emory School of Medicine,Atlanta,Vereinigte Staaten;Aflac Cancer and Blood Disorder Center of Children's Healthcare of Atlanta and Department of P
,
Margot Hottmann
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
,
Sarah Gray
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
,
Carolyn Hoppe
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
,
Mark Davis
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
Patrick Yue
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
(Abstract release date: 05/12/22) EHA Library. Andemariam B. 06/10/22; 358345; P1486
Dr. Biree Andemariam
Dr. Biree Andemariam
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1486

Type: Poster presentation

Session title: Sickle cell disease

Background
Sickle cell disease (SCD) is a group of autosomal recessive red blood cell (RBC) disorders caused by a single point mutation in the β-globin gene, resulting in the production of hemoglobin S. Hemoglobin S polymerization within deoxygenated RBCs contributes to hemolysis, vaso-occlusion, and end-organ damage. Abnormal heterocellular adhesive interactions between RBCs and endothelial cells, leukocytes, and platelets play a central role in triggering painful vaso-occlusive crises (VOCs) in patients with SCD. Inclacumab is a recombinant, fully human monoclonal antibody directed against human P-selectin, a cell adhesion molecule produced by endothelial cells and platelets. Inclacumab binding of P-selectin, and prevention of P-selectin ligand binding, interferes with the adhesion of sickle RBCs, platelets, and leukocytes to endothelium and is the putative mechanism by which inclacumab may potentially reduce the incidence of VOCs. 

Aims
We aim to conduct two global, multicenter, phase 3 studies and an open-label extension (OLE) study to evaluate the safety and efficacy of inclacumab in individuals with SCD.

Methods
THRIVE-131 (NCT04935879) is a randomized, double-blind, placebo-controlled, multicenter trial in which ~240 participants aged ≥12 years experiencing 2 to 10 VOCs in the previous 12 months will be randomized 1:1 to receive intravenous (IV) inclacumab or placebo every 12 weeks for 48 weeks (Figure). The primary endpoint is the rate of VOCs during the 48-week treatment period. THRIVE-132 (NCT04927247) is a randomized, double-blind, placebo-controlled, multicenter trial in which ~280 participants aged ≥12 years experiencing 2 to 10 VOCs in the previous 12 months will be randomized 1:1 to receive a single dose of IV inclacumab or placebo within 5 days of resolution of an index VOC that required admission to a healthcare facility and treatment with parenteral pain medication. The primary endpoint is the proportion of patients with readmission for a VOC within 90 days of randomization. After completion of their participation in THRIVE-131 or THRIVE-132, participants may enroll in THRIVE-133 OLE, evaluating the long-term safety of inclacumab. In THRIVE-133 OLE, participants will receive IV inclacumab every 12 weeks as long as the clinical benefit of treatment outweighs the risk and until access to inclacumab from an alternative source (eg, through commercialization or a managed-access program) becomes available.

Results
Recruiting for both THRIVE-131 and THRIVE-132 began in October 2021 and is ongoing.

Conclusion
The THRIVE-131 and THRIVE-132 phase 3 studies will examine the efficacy of inclacumab in reducing VOCs and readmissions due to VOCs, and the THRIVE-133 OLE study will examine the long-term safety of inclacumab in individuals with SCD.

Keyword(s): Sickle cell disease, Sickle cell patient, Vasoocclusive crisis

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1486

Type: Poster presentation

Session title: Sickle cell disease

Background
Sickle cell disease (SCD) is a group of autosomal recessive red blood cell (RBC) disorders caused by a single point mutation in the β-globin gene, resulting in the production of hemoglobin S. Hemoglobin S polymerization within deoxygenated RBCs contributes to hemolysis, vaso-occlusion, and end-organ damage. Abnormal heterocellular adhesive interactions between RBCs and endothelial cells, leukocytes, and platelets play a central role in triggering painful vaso-occlusive crises (VOCs) in patients with SCD. Inclacumab is a recombinant, fully human monoclonal antibody directed against human P-selectin, a cell adhesion molecule produced by endothelial cells and platelets. Inclacumab binding of P-selectin, and prevention of P-selectin ligand binding, interferes with the adhesion of sickle RBCs, platelets, and leukocytes to endothelium and is the putative mechanism by which inclacumab may potentially reduce the incidence of VOCs. 

Aims
We aim to conduct two global, multicenter, phase 3 studies and an open-label extension (OLE) study to evaluate the safety and efficacy of inclacumab in individuals with SCD.

Methods
THRIVE-131 (NCT04935879) is a randomized, double-blind, placebo-controlled, multicenter trial in which ~240 participants aged ≥12 years experiencing 2 to 10 VOCs in the previous 12 months will be randomized 1:1 to receive intravenous (IV) inclacumab or placebo every 12 weeks for 48 weeks (Figure). The primary endpoint is the rate of VOCs during the 48-week treatment period. THRIVE-132 (NCT04927247) is a randomized, double-blind, placebo-controlled, multicenter trial in which ~280 participants aged ≥12 years experiencing 2 to 10 VOCs in the previous 12 months will be randomized 1:1 to receive a single dose of IV inclacumab or placebo within 5 days of resolution of an index VOC that required admission to a healthcare facility and treatment with parenteral pain medication. The primary endpoint is the proportion of patients with readmission for a VOC within 90 days of randomization. After completion of their participation in THRIVE-131 or THRIVE-132, participants may enroll in THRIVE-133 OLE, evaluating the long-term safety of inclacumab. In THRIVE-133 OLE, participants will receive IV inclacumab every 12 weeks as long as the clinical benefit of treatment outweighs the risk and until access to inclacumab from an alternative source (eg, through commercialization or a managed-access program) becomes available.

Results
Recruiting for both THRIVE-131 and THRIVE-132 began in October 2021 and is ongoing.

Conclusion
The THRIVE-131 and THRIVE-132 phase 3 studies will examine the efficacy of inclacumab in reducing VOCs and readmissions due to VOCs, and the THRIVE-133 OLE study will examine the long-term safety of inclacumab in individuals with SCD.

Keyword(s): Sickle cell disease, Sickle cell patient, Vasoocclusive crisis

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