Clinical trial NCT04935879: A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sickle Cell Disease
Vaso-occlusive Pain Episode in Sickle Cell Disease
Vaso-occlusive Crisis
Keywords: blood disorders
hemoglobin
red blood cells
sickle-like shape
mutation in hemoglobin gene
sickle-cell trait
sickle-cell crisis
Sickle Cell Disease
SCD
Vaso-occlusive Crises
VOC
SCA
RBCs
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-06-23
Enrollment: 243
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of VOCs during the 48-week treatment period.
timeFrame: Day 1- Week 48
Secondary outcomes:
measure: Time to first VOC during the 48-week treatment period.
timeFrame: Day 1- Week 48
measure: Time to second VOC during the 48-week treatment period Efficacy.
timeFrame: Day 1- Week 48
measure: Proportion of participants with no VOCs during the 48-week treatment period.
timeFrame: Day 1- Week 48
measure: Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment period.
timeFrame: Day 1- Week 48
measure: Number of days of inpatient hospitalization for a VOC during the 48-week treatment period.
timeFrame: Day 1- Week 48
measure: Incidence of treatment-emergent adverse events (TEAEs).
timeFrame: Day 1- Week 48
Other outcomes:
measure: PD parameter (P-selectin inhibition)
timeFrame: Day 1- Week 48
measure: PD parameter (Platelet Leukocyte Aggregation)
timeFrame: Day 1- Week 48
Locations:
city: Mobile
country: United States
facility: University of South Alabama Children's and Women's Hospital
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Strada Patient Care Center
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital, Oakland
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Orange
country: United States
facility: UCI Center for clinical research
state: California
city: Farmington
country: United States
facility: Uconn Health/Uconn John Dempsey Hospital/Neag Comprehensive Cancer Center/New England Sickle Cell
state: Connecticut
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: USF Health South Tampa Center for Advanced Healthcare
state: Florida
city: Tampa
country: United States
facility: John S. Curran, MD.,Children's Health Center
state: Florida
city: Tampa
country: United States
facility: USF Clinical Investigational Research Pharmacy
state: Florida
city: Tampa
country: United States
facility: USF Health Carol & Frank Morsani Center for Advanced Healthcare
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Scottish Rite
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Hospital Pharmacy Services- Investigational Drug Services
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center Investigator Pharmacy
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Clinical Research Center (CRC)
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System(UI Health)
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute IDS Pharmacy
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals - Michigan Medicine
state: Michigan
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Durham
country: United States
facility: DUMC Investigational Drug Services Pharmacy
state: North Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: UT Physicians Comprehensive Sickle Cell Clinic
state: Texas
city: Houston
country: United States
facility: McGovern Medical School/Health Science Center Houston
state: Texas
city: Houston
country: United States
facility: Memorial Hermann - TMC Investigational Drugs, IDS Pharmacy
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital, Texas Medical Center - Clinical Research Unit (CRU)
state: Texas
city: Houston
country: United States
facility: UT Physicians Comprehensive Sickle Cell Clinic
state: Texas
city: Salvador
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino - Hospital São Rafael
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas da Universidade Federal de Minas Gerais
state: MG
city: Belo Horizonte
country: Brazil
facility: Hemocentro de Belo Horizonte - Fundacao Hemominas
state: MG
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas da Universidade Federal de Minas Gerais
state: Minas Gerais
city: Recife
country: Brazil
facility: Multihemo Serviços Médicos S/A
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: RS
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SAO Paulo
city: Sao Paulo
country: Brazil
facility: Comite de Etica em Pesquisa - CEP do Hospital Alemao Oswaldo Cruz/ SP
state: SP
city: Ribeirão Preto
country: Brazil
facility: Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP
state: SÃO Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO
city: São Paulo
country: Brazil
facility: Hospital Samaritano Higienópolis/Esho Empresa De Servicos Hospitalares S.A
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo-HCFMUSP
city: São Paulo
country: Brazil
facility: Casa de Saúde Santa Marcelina
city: São Paulo
country: Brazil
facility: CEPEC-Centro de Pesquisa Clinica
city: Barranquilla
country: Colombia
facility: Clinica de la Costa Ltda.
state: Atlantico
city: Barranquilla
country: Colombia
facility: Organizacion Clinica Bonnadona Prevenir S.A.S.
state: Atlántico
city: Valledupar
country: Colombia
facility: Sociedad de Oncologia y hematologia del Cesar S.A.S.
state: Cesar
city: Zagazig
country: Egypt
facility: Zagazig University Hospital
state: ASH Sharqia
city: Elmanial
country: Egypt
facility: Al Kasr Al Ainy Cairo University Hospital
state: Cairo Governorate
city: El-Rashidy Street, ElSayeda Zeinb
country: Egypt
facility: Cairo University Paediatric Hospital - abou el Reesh University Hospital
state: Cairo
city: Cairo
country: Egypt
facility: Faculty of Medicine Cairo University
city: Cairo
country: Egypt
facility: AinShams University Hospital
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du Cancer de Toulouse-Oncopole
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
city: Kumasi
country: Ghana
facility: Sickle-Cell Office, Directorate of Child Health, Komfo Anokye Teaching Hospital
state: Ashanti
city: Genova
country: Italy
facility: Farmacia Interna Azienda Ospedaliero-Ente Ospedaliero Ospedali Galliera
city: Genova
country: Italy
facility: S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro Azienda
city: Napoli
country: Italy
facility: DAI Materno-Infantile, UOC Clinica Pediatrica 1 Azienda Ospedaliera Universitaria
city: Napoli
country: Italy
facility: DAI Materno-Infantile,- UOC Clinica Pediatrica 1 Azienda Ospedaliera Universitaria "Luigi Vanvitel
city: Napoli
country: Italy
facility: UO di Farmacia Clinica, Dipartimento di Medicina Sperimentale Azienda Ospedaliera Universitaria
city: Napoli
country: Italy
facility: UOC Patologia Clinica e Molecolare Azienda Ospedaliera Universitaria "Luigi Vanvitelli"
city: Napoli
country: Italy
facility: UOC Radiologia Azienda Ospedaliera Universitaria "Luigi Vanvitelli"
city: Padova
country: Italy
facility: Dipartimento Strutturale Aziendale Salute della Donna e del Bambino Clinica Ginecologica
city: Padova
country: Italy
facility: Farmacia Azienda Ospedale Universita Padova
city: Padova
country: Italy
facility: U.O.C. Farmacia Istituto Oncologico Veneto
city: Kisumu
country: Kenya
facility: KEMRI/CRDR, Siaya, KEMRI Clinical Research Annex
state: Siaya
city: Eldoret
country: Kenya
facility: International Cancer Institute
city: Nairobi
country: Kenya
facility: Gertrude's Children Hospital
city: Nairobi
country: Kenya
facility: Kenya Medical Research Institute- Center for Respiratory Disease Research
city: Nairobi
country: Kenya
facility: Strathmore University Medical Center - Center for Research in Therapeutic Sciences(CREATES)
city: Hamra
country: Lebanon
facility: American University of Beirut Medical Center
state: Beirut
city: Tripoli
country: Lebanon
facility: Nini Hospital
state: North Lebanon
city: Calabar
country: Nigeria
facility: University of Calabar Teaching Hospital
state: Cross River State
city: Abuja
country: Nigeria
facility: National Hospital Abuja
state: FCT
city: Gwagwalada
country: Nigeria
facility: University of Abuja Teaching Hospital
state: FCT
city: Zaria
country: Nigeria
facility: Ahmadu Bello University Teaching Hospital
state: Kaduna
city: Enugu
country: Nigeria
facility: University of Nigeria Teaching Hospital
city: Kaduna
country: Nigeria
facility: Barau Dikko Teaching Hospital/Kaduna State University
city: Kano
country: Nigeria
facility: Aminu Kano Teaching Hospital
city: Lagos
country: Nigeria
facility: Department of Pediatrics, College of Medicine, Lagos University Teaching Hospital
city: Muscat
country: Oman
facility: Sultan َQaboos University Hospital
city: Jizan
country: Saudi Arabia
facility: Prince Mohammed bin Nasser Hospital
state: Southern
city: Mbeya
country: Tanzania
facility: NIMR-Mbeya Medical Research Center
city: Ankara
country: Turkey
facility: Hacettepe University
state: Altindag/sihhiye
city: Yenisehir
country: Turkey
facility: Mersin Universitesi Tip Fakultesi Saglik Arastirma ve Uygulama Merkezi Hastanesi
state: Mersin
city: Adana
country: Turkey
facility: Baskent University Hospital
state: Yuregir
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi Cocuk Hematoloji Onkoloji
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
state: London CITY OF
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: London CITY OF
city: Ndola
country: Zambia
facility: Arthur Davison Childrens's Hospital
state: Copperbelt
city: Lusaka
country: Zambia
facility: Matero Clinical Research Site,
city: Lusaka
country: Zambia
facility: University Teaching Hospital- Children's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: