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: Completed
• 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): 241
• Phase: Phase 3

Contacts and Locations

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, 01232-010
    • Hospital Samaritano Higienópolis/Esho Empresa De Servicos Hospitalares S.A
  • São Paulo, Brazil, 08270-120
    • CEPEC-Centro de Pesquisa Clinica
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Instituto D'Or de Pesquisa e Ensino - Hospital Sao Rafael
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-460
      • Multihemo Servicos Medicos S/A
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto
• Colombia
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080020
      • Clínica de la costa Ltda.
  • Cesar Department
    • Valledupar, Cesar Department, 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
• France
  • Créteil, France, 94010
    • Hopital Henri Mondor
  • Toulouse, France, 31059
    • Institut Universitaire du cancer de Toulouse-Oncopole
• 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 County
    • Kisumu, Siaya County, Kenya, 40600
      • KEMRI/CRDR, Siaya, KEMRI Clinical Research Annex
• Lebanon
  • Beyrouth
    • Hamra, Beyrouth, 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
  • Federal Capital Territory
    • Abuja, Federal Capital Territory, Nigeria, 900211
      • National Hospital Abuja
    • Gwagwalada, Federal Capital Territory, Nigeria, 902101
      • University of Abuja Teaching Hospital
  • Kaduna State
    • Zaria, Kaduna State, 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 (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Acibadem Adana Hastanesi Cocuk Hematoloji Onkoloji
  • Mersin
    • Yenişehir, Mersin, Turkey (Türkiye), 33343
      • Mersin Universitesi Tip Fakultesi Saglik Arastirma ve Uygulama Merkezi Hastanesi
  • Yuregir
    • Adana, Yuregir, Turkey (Türkiye), 01250
      • Baskent University Hospital
• 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
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States, 92868
      • UC Irvine Health
    • Orange, California, United States, 92868
      • UCI Center for Clinical Research
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Uconn Health/Uconn John Dempsey Hospital/Neag Comprehensive Cancer Center/New England Sickle Cell
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • 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)
    • Chicago, Illinois, United States, 60612
      • Hospital Pharmacy Services- Investigational Drug Services
  • 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
    • The Bronx, New York, United States, 10461
      • Jacobi 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
  • Texas
    • 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)
    • Houston, Texas, United States, 77030
      • UT Physicians Comprehensive Sickle Cell Clinic

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 Vaso-occlusive Crises (VOCs) [Adjudicated] Through Week 48	A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. The rate of VOC was defined as number of VOC events per 48 weeks and presented in this outcome measure.	Randomization (Day 1) up to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First VOC Through Week 48	A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral NSAIDs, or an increase in treatment with oral narcotics. Time to first VOC was the time between randomization date and onset date of first VOC event during 48 weeks. Kaplan-Meier method was used for estimation.	Randomization (Day 1) up to Week 48
Time to Second VOC Through Week 48	A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral NSAIDs, or an increase in treatment with oral narcotics. Time to second VOC was the time between randomization date and onset date of second VOC event during 48 weeks. Kaplan-Meier method was used for estimation.	Randomization (Day 1) up to Week 48
Percentage of Participants With no VOCs Through Week 48	A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral NSAIDs, or an increase in treatment with oral narcotics. Participants without an observed VOC who discontinued the study prior to the end of the 48-week treatment period were assumed to had experienced at least one VOC.	Randomization (Day 1) up to Week 48
Rate of VOCs Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication [Adjudicated] Through Week 48	A VOC that required admission to a healthcare facility and treatment with parenteral pain medication where admission 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. The rate of VOC was defined as number of VOC events per 48 weeks; rate of VOCs which required admission to a healthcare facility and treatment with parenteral pain medication is presented in this outcome measure.	Randomization (Day 1) up to Week 48
Rate of Inpatient Hospitalization Days for a VOC Through Week 48	A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility hospitalization. For each VOC event requiring inpatient hospitalization (regardless of treatment received) during the 48-week, the number of days hospitalized were determined based on the hospital admission and discharge dates. The rate of inpatient hospitalization days was defined as number of inpatient hospitalization days for a VOC per 48 weeks and presented in this outcome measure.	Randomization (Day 1) up to Week 48
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE was defined as an AE with an onset after the initiation of dosing for the first dose of study drug. A serious adverse events (SAE) or serious suspected adverse reaction is an AE or suspected adverse reaction that, at any dose, in the view of the either the investigator or sponsor, results in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization and congenital anomaly/birth defect. AEs included both serious and all non-SAEs.	Day 1 up to Week 60 (12 week of follow-up post 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 4, 2021
• Primary Completion (Actual): June 6, 2024
• Study Completion (Actual): June 6, 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): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

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: Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Hematologic Diseases; Sickle Cell Trait; Vaso-Occlusive Crises; inclacumab
• Other Study ID Numbers: GBT2104-131; 2020-005286-13 (EudraCT Number: CTIS (EU)); 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