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

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

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease; Vaso-occlusive Pain Episode in Sickle Cell Disease; Vaso-occlusive Crisis
• Intervention / Treatment: Drug: Inclacumab; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti - HEMORIO
  • São Paulo, Brazil, 05403-000
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo -HCFMUSP
  • São Paulo, Brazil, 08270-120
    • CEPEC-Centro de Pesquisa Clinica
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Instituto D'Or de Pesquisa e Ensino - Hospital Sao Rafael
  • PE
    • Recife, PE, Brazil, 50070-460
      • Multihemo Servicos Medicos S/A
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital De Clinicas De Porto Alegre
  • SP
    • São José Do Rio Preto, SP, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
    • São Paulo, SP, Brazil, 08270-070
      • Casa de Saude Santa Marcelina
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Clínica de la costa Ltda.
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080020
      • Organizacion Clinica Bonnadona Prevenir S.A.S.
• France
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • Créteil, France, 94010
    • Hopital Henri Mondor
• Germany
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
• Italy
  • Genova, Italy, 16128
    • S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro
  • 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
    • DAI Materno-Infantile, UOC Clinica Pediatrica 1 Azienda Ospedaliera Universitaria "Luigi Vanvitell
  • Napoli, Italy, 80138
    • UO di Farmacia Clinica, Dipartimento di Medicina Sperimentale Azienda Ospedaliera Universitaria
  • Genoa
    • Genova, Genoa, Italy, 16128
      • Farmacia Interna Azienda Ospedaliero-Ente Ospedaliero Ospedali Galliera
• Kenya
  • Eldoret, Kenya, 30100
    • International Cancer Institute
  • Nairobi, Kenya, 00100
    • Kenya medical Research Institute-centre for Respiratory Disease Research
  • Nairobi, Kenya, 00200
    • Strathmore University Medical Center - Center for Research in Therapeutic Sciences(CREATES)
  • 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, 700223
    • 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, 810107
      • Ahmadu Bello University Teaching Hospital (ABUTH)
• Oman
  • Muscat, Oman, 123
    • Sultan Qaboos University Hospital
• Saudi Arabia
  • Southern
    • Jizan, Southern, Saudi Arabia, 82943
      • Prince Mohammed bin Nasser Hospital
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hastanesi Cocuk Hematoloji Onkoloji
  • Altindag/sihhiye
    • Ankara, Altindag/sihhiye, Turkey, 06230
      • Hacettepe University
  • Mersin
    • Yenischir, Mersin, Mersin, Turkey, 33343
      • Mersin Universitesi Tip Fakultesi Saglik Arastirma ve Uygulama Merkezi Hastanesi
  • Yuregir
    • Adana, Yuregir, Turkey, 01250
      • Baskent University Hospital
• United Kingdom
  • England
    • London, England, United Kingdom, SE1 9RT
      • Guy's & Thomas' 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
      • 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
      • Children's Hospital of Orange County
  • Florida
    • Tampa, Florida, United States, 33607
      • St. Joseph's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospitals - Michigan Medicine
    • Detroit, Michigan, United States, 48202
      • Functional Fluidics, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases dba Cure 4 The Kids Foundation
  • 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
  • Virginia
    • Richmond, Virginia, United States, 23230
      • PPD Bioanalytical
• Zambia
  • Lusaka, Zambia, 10101
    • Matero Clinical Research Site,
  • Lusaka, Zambia, 10101
    • University Teaching Hospital- Children'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 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.

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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 1 VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 90 Days of Randomization	A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. An admission for a VOC 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. An acute episode of pain with no other cause other than a vaso-occlusive event included: uncomplicated VOC, acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 90 Days of Randomization	A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days was defined as the time between randomization date and onset date of first VOC event. For participants who did not experience a protocol-defined VOC within 90 days of randomization, time to first VOC was censored at the end of their time at risk (participant's end of study date or Study Day 91, whichever was earlier). An admission for a VOC 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. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD. Kaplan-Meier method used for analysis.	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91]) or censored day, whichever occurred earlier
Percentage of Participants With at Least 1 VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 30 Days of Randomization	A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. An admission for a VOC 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. An acute episode of pain with no other cause other than a vaso-occlusive event included: uncomplicated VOC, acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.	Within 30 days of randomization (randomization happened on Day 1 [Day 1 to Day 31])
Rate of VOCs Leading to a Healthcare Visit That Requires Parenteral Pain Medication or an Increase in Treatment With Oral Narcotics Within 90 Days Following Randomization	VOC leading to a healthcare visit was defined as VOC at (hospital, emergency room, clinic visit, or remote contact with a healthcare provider) that required parenteral pain medication (e.g., parenteral narcotic agents or parenteral nonsteroidal anti-inflammatory drugs [NSAIDs]), or an increased treatment with oral narcotics. Complicated VOCs included acute chest syndrome (ACS),hepatic sequestration, splenic sequestration, and priapism. For each participant, the time period at risk for evaluation of VOCs was from date of randomization to the participant's end of study date or study Day 91, whichever was earlier. In this outcome measure adjusted rates of VOCs (percentages) reported were based on estimate from a negative binomial model with the independent variable of treatment group (inclacumab, placebo) and adjusted for baseline hydroxyurea use (yes, no). All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])

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	Through Day 91
PD parameter (Platelet Leukocyte Aggregation)	To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg	Through Day 91

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): December 9, 2021
• Primary Completion (Actual): November 24, 2023
• Study Completion (Actual): November 24, 2023

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 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; VOC; SCA; RBCs; Acute; Re-admission; Vaso-occlusive Crisis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT2104-132; 2020-005287-60 (Registry Identifier: CTIS (EU)); C5361002 (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