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

Sponsor

Global Blood Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04927247

Collaborator

(none)

280

Enrollment

Locations

Arms

26.9

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Vaso-occlusive Crisis Vaso-occlusive Pain Episode in Sickle Cell Disease	Drug: Inclacumab Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double blind study

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 13, 2021

Anticipated Primary Completion Date :

Dec 11, 2023

Anticipated Study Completion Date :

Mar 11, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Re-admission for a VOC within 90 days of randomization [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

Secondary Outcome Measures

Time to first re-admission for a VOC [Within 90 days of randomization]
Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication
Readmission for a VOC within 30 days [Within 30 days of randomization]
Proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication
Rate of VOCs leading to healthcare visits [Within 90 days following randomization]
Rate of VOCs leading to a healthcare visit that requires parenteral pain medication or an increase in treatment with oral narcotics
Incidence of treatment-emergent adverse events (TEAEs) [Through Day 91]

Other Outcome Measures

PD parameter (P-selectin inhibition) [Through Day 91]
To characterize the pharmacodynamics (PD) (P-selectin inhibition) of inclacumab at 30 mg/kg
PD parameter (Platelet Leukocyte Aggregation) [Through Day 91]
To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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:
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

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.

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.
Participant is male or female, ≥ 12 years of age at the time of informed consent.
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:
Has no medically determined cause other than a vaso-occlusive event, and
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
Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics.
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.
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:

Participant is receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion).
Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to Screening.
Participant weighs > 133 kg (292 lbs.).

Other protocol-defined Inclusion/Exclusion may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Children's and Women's Hospital	Mobile	Alabama	United States	36604
2	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
3	Saint Joseph's Hospital	Tampa	Florida	United States	33607-6307
4	University of Illinois at Chicago	Chicago	Illinois	United States	60607
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135-3011
7	Jacobi Medical Center	Bronx	New York	United States	10461
8	Erie County Medical Center	Buffalo	New York	United States	14215
9	Duke University Medical Center	Durham	North Carolina	United States	27710
10	St Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
11	Hospital de Clinicas de Porto Alegre (HCPA) - PPDS	Porto Alegre		Brazil	90035-003
12	Universitätsklinikum Regensburg	Regensburg		Germany
13	E O Ospedali Galliera	Genova		Italy
14	Azienda Ospedaliera Universitaria	Napoli		Italy	80138
15	International Cancer Institute (ICI)	Eldoret		Kenya
16	Strathmore University	Nairobi		Kenya
17	American University of Beirut Medical Center	Beirut		Lebanon
18	Nini Hospital	Tripoli		Lebanon
19	National Hospital Abuja	Abuja		Nigeria
20	University of Abuja Teaching Hospital	Abuja		Nigeria
21	Baskent University Medical Faculty Adana Dr. Turgut Noyan Practice and Research Center	Adana		Nigeria
22	University of Nigeria	Enugu		Nigeria
23	Aminu Kano Teaching Hospital	Lagos		Nigeria
24	Lagos University Teaching Hospital Haematology	Suru Lere		Nigeria
25	Sultan Qaboos University Hospital	Seeb		Oman
26	Acibadem Adana Hospital	Adana		Turkey
27	Hacettepe University Ihsan Dogramaci Children's Hospital	Ankara		Turkey
28	Mersin University Medical Faculty	Mersin		Turkey