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

Phase 3

Terminated

• Conditions: Sickle Cell Disease; Vaso-occlusive Pain Episode in Sickle Cell Disease; Vaso-occlusive Crisis
• Interventions: Drug: Placebo; Drug: Inclacumab

• Registration Number: NCT04927247
• Lead Sponsor: Pfizer

Brief 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.

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study First Submitted: 2021-05-26
• Study First Submitted QC: 2021-06-10
• Study First Posted: 2021-06-15
• Study Start: 2021-12-09
• Primary Completion: 2023-11-24
• Study Completion: 2023-11-24
• Status Verified: 2024-11
• Results First Submitted: 2024-11-20
• Results First Submitted QC: 2024-11-20
• Last Update Submitted: 2024-11-20
• Results First Posted: 2024-12-11
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 72

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Placebo administered IV
inclacumab 30 mg/kg	Inclacumab	Inclacumab 30 mg/kg administered intravenously (IV)

Primary Outcome Measures

Name	Time	Method
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	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])	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.

Secondary Outcome Measures

Name	Time	Method
Time to First VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 90 Days of Randomization	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91]) or censored day, whichever occurred earlier	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.
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	Within 30 days of randomization (randomization happened on Day 1 [Day 1 to Day 31])	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.
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	Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])	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.

Trial Locations

Locations (59)

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

Strada Patient Care Center; 🇺🇸 Mobile, Alabama, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

UCSF Benioff Children's Hospital, Oakland; 🇺🇸 Oakland, California, United States

Erie County Medical Center; 🇺🇸 Buffalo, New York, United States

Casa de Saude Santa Marcelina; 🇧🇷 São Paulo, SP, Brazil

Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti - HEMORIO; 🇧🇷 Rio de Janeiro, Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo -HCFMUSP; 🇧🇷 São Paulo, Brazil

Clinica de la Costa Ltda.; 🇨🇴 Barranquilla, Atlantico, Colombia

Hopital Henri Mondor; 🇫🇷 Créteil, France

CEPEC-Centro de Pesquisa Clinica; 🇧🇷 São Paulo, Brazil

Hopital Avicenne; 🇫🇷 Bobigny, France

Universitatsklinikum Regensburg Padiatrische Hamatologie, Onkologie und Stammzelltransplantation; 🇩🇪 Regensburg, Germany

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, Italy

Strathmore University Medical Center - Center for Research in Therapeutic Sciences(CREATES); 🇰🇪 Nairobi, Kenya

University of Calabar Teaching Hospital; 🇳🇬 Calabar, Cross River State, Nigeria

National Hospital Abuja; 🇳🇬 Abuja, FCT, Nigeria

Ahmadu Bello University Teaching Hospital (ABUTH); 🇳🇬 Zaria, Kaduna, Nigeria

University of Nigeria Teaching Hospital; 🇳🇬 Enugu, Nigeria

Barau Dikko Teaching Hospital/Kaduna State University; 🇳🇬 Kaduna, Nigeria

Aminu Kano Teaching Hospital; 🇳🇬 Kano, Nigeria

Hacettepe University; 🇹🇷 Ankara, Altindag/sihhiye, Turkey

Sultan Qaboos University Hospital; 🇴🇲 Muscat, Oman

Baskent University Hospital; 🇹🇷 Adana, Yuregir, Turkey

Guy's & Thomas' NHS Foundation Trust; 🇬🇧 London, England, United Kingdom

Acibadem Adana Hastanesi Cocuk Hematoloji Onkoloji; 🇹🇷 Adana, Turkey

Matero Clinical Research Site,; 🇿🇲 Lusaka, Zambia

Instituto D'Or de Pesquisa e Ensino - Hospital São Rafael; 🇧🇷 Salvador, Bahia, Brazil

Kemri/Crdr, Siaya, Kemri Clinical Research Annex,; 🇰🇪 Kisumu, Siaya, Kenya

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

Nini Hospital; 🇱🇧 Tripoli, North Lebanon, Lebanon

Department of Pediatrics, College of Medicine, Lagos University Teaching Hospital; 🇳🇬 Lagos, Nigeria

Mersin Universitesi Tip Fakultesi Saglik Arastirma ve Uygulama Merkezi Hastanesi; 🇹🇷 Yenischir, Mersin, Mersin, Turkey

University of Abuja Teaching Hospital; 🇳🇬 Gwagwalada, FCT, Nigeria

Prince Mohammed bin Nasser Hospital; 🇸🇦 Jizan, Southern, Saudi Arabia

International Cancer Institute; 🇰🇪 Eldoret, Kenya

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

Organizacion Clinica Bonnadona Prevenir S.A.S.; 🇨🇴 Barranquilla, Atlántico, Colombia

Kenya medical Research Institute-centre for Respiratory Disease Research; 🇰🇪 Nairobi, Kenya

American University of Beirut Medical Center; 🇱🇧 Hamra, Beirut, Lebanon

University Teaching Hospital- Children's Hospital; 🇿🇲 Lusaka, Zambia

Multihemo Servicos Medicos S/A; 🇧🇷 Recife, PE, Brazil

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto; 🇧🇷 São José Do Rio Preto, SP, Brazil

DUMC Investigational Drug Services Pharmacy; 🇺🇸 Durham, North Carolina, United States

St. Joseph's Hospital; 🇺🇸 Tampa, Florida, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

University of Michigan Hospitals - Michigan Medicine; 🇺🇸 Ann Arbor, Michigan, United States

Functional Fluidics, Inc.; 🇺🇸 Detroit, Michigan, United States

Alliance for Childhood Diseases dba Cure 4 The Kids Foundation; 🇺🇸 Las Vegas, Nevada, United States

PPD Bioanalytical; 🇺🇸 Richmond, Virginia, United States

Jacobi Medical Center; 🇺🇸 Bronx, New York, United States