Clinical Trials Register

Summary
EudraCT Number:	2020-005286-13
Sponsor's Protocol Code Number:	GBT2104-131
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-06-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2020-005286-13

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

GBT2104-131

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04935879

A.5.4

Other Identifiers

Name:

US IND number

Number:

144073

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Global Blood Therapeutics, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Global Blood Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Global Blood Therapeutics, Inc.
B.5.2	Functional name of contact point	Supriya Rao
B.5.3	Address:
B.5.3.1	Street Address	181 Oyster Point Blvd.
B.5.3.2	Town/ city	South San Francisco
B.5.3.3	Post code	CA 94080
B.5.3.4	Country	United States
B.5.4	Telephone number	001650351 4760
B.5.6	E-mail	srao@gbt.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Inclacumab
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Inclacumab
D.3.9.1	CAS number	1256258-86-2
D.3.9.3	Other descriptive name	Anti P-selectin glycoprotein ligand-1 humanised monoclonal antibody
D.3.9.4	EV Substance Code	SUB205263
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500 mg/ 10 mL
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sickle Cell Disease

E.1.1.1

Medical condition in easily understood language

Sickle Cell Disease in participants experiencing Vaso-occlusive Crises

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10040644
E.1.2	Term	Sickle cell disease
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the safety and efficacy of treatment every 12 weeks with inclacumab to reduce the incidence of VOCs in participants with SCD.

E.2.2

Secondary objectives of the trial

Additional objectives of the study are to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of inclacumab, the presence of anti-drug antibodies (ADAs), and changes in quality of life (QOL).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participant has a confirmed diagnosis of SCD (HbSS, HbSC, HbSβ0 thalassemia, or HbSβ+ 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, ≥ 18 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 that:
• 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 NSAIDs, or an increase in treatment with oral narcotics.
4. Participants receiving ESA (eg, 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 HU, L-glutamine, or voxelotor 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.
6. Participant has adequate venous access, in the opinion of the Investigator, to comply with study procedures.
7. Participant understands the study procedures and agrees to participate in the study by giving written informed consent or parental permission/written assent.
8. Women of childbearing potential (WOCBP) are required to have a negative serum pregnancy test at the Screening Visit and negative urine pregnancy test on all subsequent clinic visits and must agree to use a highly effective method of contraception throughout the study period and
for at least 165 days after dosing.
Female participants will not be considered of childbearing potential if they are pre-menarchal, surgically sterile (hysterectomy, bilateral salpingectomy, tubal ligation, or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause, confirmed by follicle stimulating hormone [FSH] test results).

E.4

Principal exclusion criteria

1. Participant is receiving regularly scheduled 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.).
4. Participant has a significant active and poorly controlled (unstable) hepatic disorder clearly unrelated to SCD.
5. Participant has any of the following laboratory values at screening:
a. Absolute neutrophil count (ANC) < 1.0 × 109/L
b. Platelet count < 80 × 109/L
c. Hemoglobin < 4.0 g/dL
d. Estimated glomerular filtration rate (eGFR) < 30 mL/min using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula
6. Participant has known active (symptomatic) COVID-19 infection or tests positive for COVID-19 during Screening.
7. Participant has a history of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including severe or unstable pulmonary hypertension.
8. Participant has had treatment for a malignancy within the 12 months prior to the Screening Visit (except non-melanoma skin cancer and in situ cervical cancers).
9. Participant has had a stroke within the 2 years prior to the Screening Visit.
10. Participant has a positive test indicative of malaria infection at Screening. Testing to be conducted at local laboratories in malaria-endemic regions at the discretion of the Investigator.
11. Participant has any confirmed clinically significant drug allergy and/or known hypersensitivity to monoclonal antibody therapeutics or formulation components of the study drug or a related drug.
12. Participant has been in another investigational trial within 30 days or 5 half-lives of the investigational agent (whichever is greater) prior to the Screening Visit.
13. Participant has had a major surgery within 8 weeks prior to the Screening Visit.
14. Participant is pregnant, breastfeeding, or planning to become pregnant during the 48-week treatment period.
15. Participant, parent, or legal guardian are unlikely to comply with the study procedures.
16. Participant has any other medical, psychological, or behavioral conditions that, in the opinion of the Investigator, would confound or interfere with evaluation of safety, efficacy, and/or PK of the investigational drug; prevent compliance with the study protocol; preclude informed consent; or render the participant, parent, or caretaker unable/unlikely to comply with the study procedures.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint for the study is the 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 nonsteroidal anti-inflammatory 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.
To ensure consistency across study sites, all VOCs identified will be adjudicated by an independent, blinded panel comprised of experts in SCD. The primary efficacy analysis will be performed on adjudicated data.

E.5.1.1

Timepoint(s) of evaluation of this end point

48 week treatment period

E.5.2

Secondary end point(s)

• Time to first VOC during the 48-week treatment period.
• Time to second VOC during the 48-week treatment period.
• Proportion of participants with no VOCs during the 48-week treatment period.
• Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment period where admission 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, or
• Number of days of inpatient hospitalization for a VOC during the 48-week treatment period.

E.5.2.1

Timepoint(s) of evaluation of this end point

48-week treatment period

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Colombia

Egypt

Ghana

Kenya

Lebanon

Nigeria

Oman

Saudi Arabia

Tanzania, United Republic of

United States

Zambia

France

Germany

Italy

Turkey

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

227

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

240

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Participants not enrolling in the OLE study will complete the study at the time of the last scheduled study procedures at the Week 60 visit. For participants who enroll into the OLE study, the Week 48 visit will be the final study visit. Participants will receive their first dose in the OLE study on the same day as the completion of the Week 48 visit.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-07-28

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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