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

Sponsor

Global Blood Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04935879

Collaborator

(none)

240

Enrollment

Locations

Arms

30.1

Anticipated Duration (Months)

4.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

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

Actual Study Start Date :

Oct 26, 2021

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: inclacumab, 30 mg/kg Participants will receive inclacumab 30 mg/kg administered IV every 12 weeks	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 Participants will receive placebo administered IV every 12 weeks.	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

Participants will receive inclacumab 30 mg/kg administered IV every 12 weeks

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

Participants will receive placebo administered IV every 12 weeks.

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

Rate of VOCs during the 48-week treatment period. [Day 1- Week 48]
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

Secondary Outcome Measures

Time to first VOC during the 48-week treatment period. [Day 1- Week 48]
Time to second VOC during the 48-week treatment period Efficacy. [Day 1- Week 48]
Proportion of participants with no VOCs during the 48-week treatment period. [Day 1- Week 48]
Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment period. [Day 1- Week 48]
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.
Number of days of inpatient hospitalization for a VOC during the 48-week treatment period. [Day 1- Week 48]
Incidence of treatment-emergent adverse events (TEAEs). [Day 1- Week 48]

Other Outcome Measures

PD parameter (P-selectin inhibition) [Day 1- Week 48]
To characterize the pharmacodynamics (PD) (P-selectin inhibition) of inclacumab at 30 mg/kg
PD parameter (Platelet Leukocyte Aggregation) [Day 1- Week 48]
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 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.

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 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.

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.
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:

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 the Screening Visit
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	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
4	UC Irvine Medical Center	Irvine	California	United States	92868
5	UCSF Benioff Children's Hospital	Oakland	California	United States	94609
6	University of South Florida	Tampa	Florida	United States	33606
7	Children's Healthcare of Atlanta at Scottish Rite Hospital	Atlanta	Georgia	United States	30342
8	University of Illinois at Chicago	Chicago	Illinois	United States	60607
9	Rush University Medical Center	Chicago	Illinois	United States	60612
10	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
11	University of Michigan	Ann Arbor	Michigan	United States	48109
12	Jacobi Medical Center	Bronx	New York	United States	10461
13	Erie County Medical Center	Buffalo	New York	United States	14215
14	Duke University Medical Center	Durham	North Carolina	United States	27710
15	St Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
16	Hospital de Clinicas de Porto Alegre (HCPA) - PPDS	Porto Alegre	Rio Grande Do Sul	Brazil	90035
17	Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP	Ribeirão Preto	São Paulo	Brazil
18	Fundação Faculdade Regional de Medicina de São José Do Rio Preto	São José Do Rio Preto	São Paulo	Brazil	15090-000
19	HEMORIO - Unidade de Pesquisa Clínica	Rio De Janeiro		Brazil
20	Hospital Samaritano	São Paulo		Brazil
21	Hospital Santa Marcelina	São Paulo		Brazil
22	CHU de Toulouse - IUCT ONCOPOLE	Toulouse	Haute-Garonne	France	31000
23	Hopital Avicenne	Bobigny	Seine-Saint-Denis	France	93000
24	Hopital Henri Mondor	Créteil	Val-de-Marne	France	94010
25	Universitätsklinikum Regensburg	Regensburg	Bayern	Germany	93053
26	E O Ospedali Galliera	Genova	Liguria	Italy	16128
27	Azienda Ospedale Università Padova	Padova	Veneto	Italy	35128
28	Azienda Ospedaliera Universitaria (AOU) dell'Università degli Studi della Campania Luigi Vanvitelli	Napoli		Italy	80138
29	KEMRI/CRDR Siaya Clinical Research Annex	Siaya	Nyanza	Kenya	144
30	Strathmore University	Kisumu	Western	Kenya
31	International Cancer Institute (ICI)	Eldoret		Kenya
32	KEMRI CRDR Clinical Research Clinic Nairobi	Nairobi		Kenya	0100
33	Gertrude's Children's Hospital	Nairobi		Kenya	42325
34	American University of Beirut Medical Center	Beirut		Lebanon
35	Nini Hospital	Tripoli		Lebanon
36	University of Calabar Teaching Hospital	Calabar	Cross River	Nigeria
37	Lagos University Teaching Hospital Haematology	Idi Araba	Lagos	Nigeria
38	University of Abuja Teaching Hospital	Abuja		Nigeria
39	University of Nigeria	Enugu		Nigeria
40	Aminu Kano Teaching Hospital	Kano		Nigeria
41	Sultan Qaboos University Hospital	Muscat	Al-Khodh	Oman
42	Prince Mohamed Bin Nasser Hospital	Jazan		Saudi Arabia	82943
43	NIMR-Mbeya Medical Research Center	Mbeya		Tanzania	2410
44	Baskent University Medical Faculty Adana Dr. Turgut Noyan Practice and Research Center	Adana		Turkey	01120
45	Acibadem Adana Hospital	Adana		Turkey
46	Hacettepe University Ihsan Dogramaci Children's Hospital	Ankara		Turkey
47	Mersin University Medical Faculty	Mersin		Turkey
48	Guys Hospital	London		United Kingdom	SE1 9RT
49	Kings College Hospital	London		United Kingdom