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

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sickle Cell Disease; Vaso-occlusive Pain Episode in Sickle Cell Disease; Vaso-occlusive Crisis
• Intervention / Treatment: Drug: Inclacumab; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Carolyn Hoppe, MD; Phone Number: 650-822-8728; Email: THRIVEstudy@gbt.com

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO
  • São Paulo, Brazil, 08270-070
    • Casa de Saude Santa Marcelina
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP
  • São Paulo, Brazil, 01232-010
    • Hospital Samaritano Higienópolis/Esho Empresa De Servicos Hospitalares S.A
  • São Paulo, Brazil, 08270-120
    • CEPEC-Centro de Pesquisa Clinica
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Instituto D'Or de Pesquisa e Ensino - Hospital São Rafael
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Hospital das Clinicas da Universidade Federal de Minas Gerais
    • Belo Horizonte, MG, Brazil, 30130-110
      • Hemocentro de Belo Horizonte - Fundacao Hemominas
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital das Clinicas da Universidade Federal de Minas Gerais
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-460
      • Multihemo Servicos Medicos S/A
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
  • SAO Paulo
    • Sao Jose do Rio Preto, SAO Paulo, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
  • SP
    • Sao Paulo, SP, Brazil, 01323-903
      • Comite de Etica em Pesquisa - CEP do Hospital Alemao Oswaldo Cruz/ SP
  • SÃO Paulo
    • Ribeirão Preto, SÃO Paulo, Brazil, 14051-140
      • Hospital Das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Clínica de la Costa Ltda.
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080020
      • Organizacion Clinica Bonnadona Prevenir S.A.S.
  • Cesar
    • Valledupar, Cesar, Colombia, 200001
      • Sociedad de Oncologia y hematologia del Cesar S.A.S.
• Egypt
  • Cairo, Egypt, 11562
    • Faculty of Medicine Cairo University
  • Cairo, Egypt, 11588
    • AinShams University Hospital
  • ASH Sharqia
    • Zagazig, ASH Sharqia, Egypt, 44519
      • Zagazig University Hospital
  • Cairo
    • El-Rashidy Street, ElSayeda Zeinb, Cairo, Egypt, 11617
      • Cairo University Paediatric Hospital - abou el Reesh University Hospital
  • Cairo Governorate
    • Elmanial, Cairo Governorate, Egypt, 11562
      • Al Kasr Al Ainy Cairo University Hospital
• France
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Toulouse Cedex 9, France, 31059
    • Institut Universitaire du Cancer de Toulouse-Oncopole
• Germany
  • Regensburg, Germany, 93053
    • Universitatsklinikum Regensburg Padiatrische Hamatologie, Onkologie und Stammzelltransplantation
• Ghana
  • Ashanti
    • Kumasi, Ashanti, Ghana
      • Sickle-Cell Office, Directorate of Child Health, Komfo Anokye Teaching Hospital
• Italy
  • Genova, Italy, 16128
    • Farmacia Interna Azienda Ospedaliero-Ente Ospedaliero Ospedali Galliera
  • Genova, Italy, 16128
    • S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro Azienda
  • Napoli, Italy, 80138
    • DAI Materno-Infantile,- UOC Clinica Pediatrica 1 Azienda Ospedaliera Universitaria "Luigi Vanvitel
  • Napoli, Italy, 80138
    • UOC Patologia Clinica e Molecolare Azienda Ospedaliera Universitaria "Luigi Vanvitelli"
  • Napoli, Italy, 80138
    • UOC Radiologia Azienda Ospedaliera Universitaria "Luigi Vanvitelli"
  • Napoli, Italy, 80138
    • UO di Farmacia Clinica, Dipartimento di Medicina Sperimentale Azienda Ospedaliera Universitaria
  • Napoli, Italy, 80138
    • DAI Materno-Infantile, UOC Clinica Pediatrica 1 Azienda Ospedaliera Universitaria
  • Padova, Italy, 35128
    • Dipartimento Strutturale Aziendale Salute della Donna e del Bambino Clinica Ginecologica
  • Padova, Italy, 35128
    • Farmacia Azienda Ospedale Universita Padova
  • Padova, Italy, 35128
    • U.O.C. Farmacia Istituto Oncologico Veneto
• Kenya
  • Eldoret, Kenya, 30100
    • International Cancer Institute
  • Nairobi, Kenya, 00200
    • Strathmore University Medical Center - Center for Research in Therapeutic Sciences(CREATES)
  • Nairobi, Kenya, 00100
    • Gertrude's Children Hospital
  • Nairobi, Kenya, 00100
    • Kenya Medical Research Institute- Center for Respiratory Disease Research
  • Siaya
    • Kisumu, Siaya, Kenya, 40600
      • KEMRI/CRDR, Siaya, KEMRI Clinical Research Annex
• Lebanon
  • Beirut
    • Hamra, Beirut, Lebanon
      • American University of Beirut Medical Center
  • North Lebanon
    • Tripoli, North Lebanon, Lebanon
      • Nini Hospital
• Nigeria
  • Enugu, Nigeria, 460000
    • University of Nigeria Teaching Hospital
  • Kaduna, Nigeria, 800212
    • Barau Dikko Teaching Hospital/Kaduna State University
  • Kano, Nigeria, 700233
    • Aminu Kano Teaching Hospital
  • Lagos, Nigeria, 100254
    • Department of Pediatrics, College of Medicine, Lagos University Teaching Hospital
  • Cross River State
    • Calabar, Cross River State, Nigeria, 540242
      • University of Calabar Teaching Hospital
  • FCT
    • Abuja, FCT, Nigeria, 900211
      • National Hospital Abuja
    • Gwagwalada, FCT, Nigeria, 902101
      • University of Abuja Teaching Hospital
  • Kaduna
    • Zaria, Kaduna, Nigeria, 1100011
      • Ahmadu Bello University Teaching Hospital
• Oman
  • Muscat, Oman, 123
    • Sultan Qaboos University Hospital
• Saudi Arabia
  • Southern
    • Jizan, Southern, Saudi Arabia, 82943
      • Prince Mohammed bin Nasser Hospital
• Tanzania
  • Mbeya, Tanzania
    • NIMR-Mbeya Medical Research Center
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hastanesi Cocuk Hematoloji Onkoloji
  • Altindag/sihhiye
    • Ankara, Altindag/sihhiye, Turkey, 06230
      • Hacettepe University
  • Mersin
    • Yenisehir, Mersin, Turkey, 33343
      • Mersin Universitesi Tip Fakultesi Saglik Arastirma ve Uygulama Merkezi Hastanesi
  • Yuregir
    • Adana, Yuregir, Turkey, 01250
      • Baskent University Hospital
• United Kingdom
  • London CITY OF
    • London, London CITY OF, United Kingdom, SE1 9RT
      • Guy's and St Thomas' NHS Foundation Trust
    • London, London CITY OF, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Mitchell Cancer Institute
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Children's and Women's Hospital
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Strada Patient Care Center
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital, Oakland
    • Orange, California, United States, 92868-3201
      • UC Irvine Health
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1163
      • Uconn Health/Uconn John Dempsey Hospital/Neag Comprehensive Cancer Center/New England Sickle Cell
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
    • Tampa, Florida, United States, 33606
      • USF Health South Tampa Center for Advanced Healthcare
    • Tampa, Florida, United States, 33612
      • John S. Curran, MD.,Children's Health Center
    • Tampa, Florida, United States, 33612
      • USF Clinical Investigational Research Pharmacy
    • Tampa, Florida, United States, 33612
      • USF Health Carol & Frank Morsani Center for Advanced Healthcare
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta - Scottish Rite
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612-4333
      • Hospital Pharmacy Services- Investigational Drug Services
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Investigator Pharmacy
    • Chicago, Illinois, United States, 60612
      • University of Illinois Clinical Research Center (CRC)
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital and Health Sciences System(UI Health)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute IDS Pharmacy
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospitals - Michigan Medicine
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27710
      • DUMC Investigational Drug Services Pharmacy
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77004
      • UT Physicians Comprehensive Sickle Cell Clinic
    • Houston, Texas, United States, 77030
      • McGovern Medical School/Health Science Center Houston
    • Houston, Texas, United States, 77030
      • Memorial Hermann - TMC Investigational Drugs, IDS Pharmacy
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital, Texas Medical Center - Clinical Research Unit (CRU)
• Zambia
  • Lusaka, Zambia, 10101
    • Matero Clinical Research Site,
  • Lusaka, Zambia, 10101
    • University Teaching Hospital- Children's Hospital
  • Copperbelt
    • Ndola, Copperbelt, Zambia, 10101
      • Arthur Davison Childrens's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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.

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

3. 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.
4. 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.
5. 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:

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 the Screening Visit
3. Participant weighs > 133 kg (292 lbs.).

Other protocol-defined Inclusion/Exclusion may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: inclacumab, 30 mg/kg; Participants will receive inclacumab 30 mg/kg administered IV every 12 weeks	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; Participants will receive placebo administered IV every 12 weeks.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of VOCs during the 48-week treatment period.	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	Day 1- Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first VOC during the 48-week treatment period.		Day 1- Week 48
Time to second VOC during the 48-week treatment period Efficacy.		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.	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.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD parameter (P-selectin inhibition)	To characterize the pharmacodynamics (PD) (P-selectin inhibition) of inclacumab at 30 mg/kg	Day 1- Week 48
PD parameter (Platelet Leukocyte Aggregation)	To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg	Day 1- Week 48

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Estimated): August 15, 2024
• Study Completion (Estimated): August 15, 2024

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: hemoglobin; Sickle Cell Disease; SCD; blood disorders; red blood cells; sickle-like shape; mutation in hemoglobin gene; sickle-cell trait; sickle-cell crisis; Vaso-occlusive Crises; VOC; SCA; RBCs
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT2104-131; 2020-005286-13 (Registry Identifier: CTIS (EU)); LBCTR2021054791 (Registry Identifier: Lebanon Clinical Trials Registry); C5361001 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No