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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04927247
• Other study ID #: GBT2104-132
• Secondary ID: C53610022020-005
• Status: Terminated
• Phase: Phase 3
• Start date: December 13, 2021
• Est. completion date: November 24, 2023

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 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: November 24, 2023
• Est. primary completion date: November 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

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	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS
Brazil	Multihemo Servicos Medicos S/A	Recife	PE
Brazil	Instituto Estadual de Hematologia Arthur de 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	São José Do Rio Preto	SP
Brazil	Casa de Saude Santa Marcelina	São Paulo	SP
Brazil	CEPEC-Centro de Pesquisa Clinica	São Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo -HCFMUSP	São Paulo
Colombia	Clinica de la Costa Ltda.	Barranquilla	Atlantico
Colombia	Organizacion Clinica Bonnadona Prevenir S.A.S.	Barranquilla	Atlántico
France	Hopital Avicenne	Bobigny
France	Hopital Henri Mondor	Créteil
Germany	Universitatsklinikum Regensburg Padiatrische Hamatologie, Onkologie und Stammzelltransplantation	Regensburg
Italy	Farmacia Interna Azienda Ospedaliero-Ente Ospedaliero Ospedali Galliera	Genova	Genoa
Italy	S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro	Genova
Italy	DAI Materno-Infantile, UOC Clinica Pediatrica 1 Azienda Ospedaliera Universitaria "Luigi Vanvitell	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
Kenya	International Cancer Institute	Eldoret
Kenya	Kemri/Crdr, Siaya, Kemri Clinical Research Annex,	Kisumu	Siaya
Kenya	Kenya medical Research Institute-centre 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 (ABUTH)	Zaria	Kaduna
Oman	Sultan Qaboos University Hospital	Muscat
Saudi Arabia	Prince Mohammed bin Nasser Hospital	Jizan	Southern
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	Yenischir, Mersin	Mersin
United Kingdom	Guy's & Thomas' NHS Foundation Trust	London	England
United States	University of Michigan Hospitals - Michigan Medicine	Ann Arbor	Michigan
United States	Jacobi Medical Center	Bronx	New York
United States	Erie County Medical Center	Buffalo	New York
United States	Functional Fluidics, Inc.	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	DUMC Investigational Drug Services Pharmacy	Durham	North Carolina
United States	Alliance for Childhood Diseases dba Cure 4 The Kids Foundation	Las Vegas	Nevada
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Strada Patient Care Center	Mobile	Alabama
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	UCSF Benioff Children's Hospital, Oakland	Oakland	California
United States	Children's Hospital of Orange County	Orange	California
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	PPD Bioanalytical	Richmond	Virginia
United States	St. Joseph's Hospital	Tampa	Florida
Zambia	Matero Clinical Research Site,	Lusaka
Zambia	University Teaching Hospital- Children's Hospital	Lusaka

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Zambia,  Brazil,  Colombia,  France,  Germany,  Italy,  Kenya,  Lebanon,  Nigeria,  Oman,  Saudi Arabia,  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	Through Day 91
Other	PD parameter (Platelet Leukocyte Aggregation)	To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg	Through Day 91
Primary	Re-admission for a VOC within 90 days of randomization	Following an index VOC, the proportion 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
Secondary	Time to first re-admission for a VOC	Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication	Within 90 days of randomization
Secondary	Readmission for a VOC within 30 days	Proportion 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
Secondary	Rate of VOCs leading to healthcare visits	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
Secondary	Incidence of treatment-emergent adverse events (TEAEs)		Through Day 91

External Links

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