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

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04935879
• Other study ID #: GBT2104-131
• Secondary ID: C53610012020-005
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 26, 2021
• Est. completion date: August 15, 2024

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: August 15, 2024
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Vaso-occlusive Crisis
• Vaso-occlusive Pain Episode in Sickle Cell Disease

Intervention

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
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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Zambia,  Brazil,  Colombia,  Egypt,  France,  Germany,  Ghana,  Italy,  Kenya,  Lebanon,  Nigeria,  Oman,  Saudi Arabia,  Tanzania,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PD parameter (P-selectin inhibition)	To characterize the pharmacodynamics (PD) (P-selectin inhibition) of inclacumab at 30 mg/kg	Day 1- Week 48
Other	PD parameter (Platelet Leukocyte Aggregation)	To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg	Day 1- Week 48
Primary	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	Time to first VOC during the 48-week treatment period.		Day 1- Week 48
Secondary	Time to second VOC during the 48-week treatment period Efficacy.		Day 1- Week 48
Secondary	Proportion of participants with no VOCs during the 48-week treatment period.		Day 1- Week 48
Secondary	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
Secondary	Number of days of inpatient hospitalization for a VOC during the 48-week treatment period.		Day 1- Week 48
Secondary	Incidence of treatment-emergent adverse events (TEAEs).		Day 1- Week 48

External Links

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