Clinical Trials Register

Summary
EudraCT Number:	2021-002148-56
Sponsor's Protocol Code Number:	ACT-CS-005
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-07-25
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2021-002148-56

A.3

Full title of the trial

A RANDOMIZED, DOUBLE BLIND, MULTICENTER, MULTINATIONAL, PLACEBO CONTROLLED, PARALLEL GROUP, SINGLE DOSE, ADAPTIVE EFFICACY AND SAFETY STUDY OF GLENZOCIMAB USED AS AN ADD-ON THERAPY ON TOP OF STANDARD OF CARE IN THE 4.5 HOURS FOLLOWING AN ACUTE ISCHEMIC STROKE

A.3.1

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

ADAPTIVE EFFICACY AND SAFETY STUDY OF GLENZOCIMAB USED AS AN ADD-ON THERAPY ON TOP OF STANDARD OF CARE IN THE 4.5 HOURS FOLLOWING AN ACUTE ISCHEMIC STROKE

A.3.2

Name or abbreviated title of the trial where available

ACTISAVE

A.4.1

Sponsor's protocol code number

ACT-CS-005

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05070260

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	ACTICOR BIOTECH
B.1.3.4	Country	France
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	ACTICOR BIOTECH
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ACTICOR BIOTECH
B.5.2	Functional name of contact point	Regulatory Affairs Manager
B.5.3	Address:
B.5.3.1	Street Address	WOJO Building, 82, avenue du Maine
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75014
B.5.3.4	Country	France
B.5.4	Telephone number	33665460479
B.5.6	E-mail	jessica.jami@acticor-biotech.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	glenzocimab
D.3.2	Product code	ACT017
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	Glenzocimab
D.3.9.1	CAS number	2101829-58-5
D.3.9.4	EV Substance Code	SUB201813
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	10
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	Yes
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 injection
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

Acute ischemic stroke

E.1.1.1

Medical condition in easily understood language

Ischemic Stroke is defined as an acute neurologic deficit caused by
vascular occlusion or stenosis

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	22.1
E.1.2	Level	LLT
E.1.2	Classification code	10055221
E.1.2	Term	Ischemic stroke
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To show the efficacy of glenzocimab vs. placebo, on the "poor outcome" defined as a mRS score of 4-6 (vs 0-3) assessed at Day 90

E.2.2

Secondary objectives of the trial

Key sec obj: To show the efficacy of glenzocimab vs. placebo on the "favorable outcome" defined as an mRS score of 0-2 (vs 3-6) assessed at Day 90.
Other sec obj: To assess the efficacy of glenzocimab vs. placebo on the:
•mRS 5-6 at Day 90
•mRS 0-1 at Day 90
•Ordinal mRS at Day 90
• Utility weighted mRS (UW-mRS) at Day 90
• Change from baseline in the National Institute of Health Stroke Scale (NIHSS) score at Day 1
•All-cause mortality within 72 hours
•All-cause mortality at Day 90
•Symptomatic and non-symptomatic ICHs
• To assess recanalization in patients undergoing thrombectomy
• To assess cerebral tissue reperfusion
• To assess the impact on follow up imaging (follow up infarct volume, infarct growth and volume of hemorrhagic transformation)
To assess the efficacy of glenzocimab vs. placebo of all endpoints, in specific subgroups: subjects who will receive thrombectomy vs who will not, by age level, baseline NIHSS level and thrombolytic agent, if feasible.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization).
2. Having given their own written consent or legal representative's consent, or emergency consent, and in any case, in strict accordance with country-specific legal requirements.
3. Presenting with an acute disabling ischemic stroke either in the anterior or in posterior circulation, with or without visible occlusion, with a known time of onset, that is ≤ 4.5 hrs
4. Presenting with a pre-IVT NIHSS ≥ 6
5. In whom IVT is or has been initiated, whether or not patients are additionally eligible to mechanical thrombectomy (MT+IVT), according to the recommendation of the last guidelines (ASA and ESO recommendations),
6. Women of childbearing potential (WOCBP) must have a negative serum/urine pregnancy test at baseline. Women of childbearing potential, i.e, fertile, are defined as women following menarche and until becoming post-menopausal unless permanently sterile, i.e, having undergone hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
7. Post-menopausal women defined as not having menses for 12 months without an alternative medical cause. For WOCBP, a highly effective birth control method shoudl be in place that can achieve a failure rate of less than 1% per year that should last for at least 2 months after IMP
administration.
Birth control methods which may be considered as highly effective in WOCBP include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (intravaginal, transdermal),
• Progestogen-only hormonal contraception associated with inhibition of ovulation (injectable, implantable)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion,
• vasectomized partner,
Birth control methods which may be considered as highly effective for men and that should last for 4 months after IMP administration include:
• vasectomy,
• use of condom combined with a highly effective birth control method for their WOCBP partner.
Please note that hormonal contraception is a risk factor for thromboembolic events and attention should be called to reconsider it passed the acute stroke phase.
8. Patients affiliated to a health insurance - modality depending on country legal requirements

E.4

Principal exclusion criteria

1. Coma, or NIHSS >25
2. Patients < 18 years
3. Protected adults under guardanship or curatorship
4. Prior ischemic stroke within the past 3 months
5. mRS pre-stroke known to be ≥ 2
6. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on Baseline Computed Tomography Angiography (CTA) or Magnetic Resonance Imaging with vascular injection (MRA).
7. Significant mass effect with midline shift
8. Stroke of hemorrhagic origin
9. Patients likely to require dual antiplatelet therapy (DAPT) within the first 24 hrs after cessation of glenzocimab or placebo infusion for e.g., carotid stenting
10. Known renal insufficiency (Grades 4-5 – severe or terminal), with a creatinine clearance < 30 mL/Mn using Cockroft formula)
11. Known allergic reaction to contrast agents
12. Known ongoing anti-coagulant therapy, except preventative doses of injectable low molecular weight heparin (LMWH)
13. Known ongoing treatment with a mAb.
14. Prior cardiopulmonary resuscitation < 10 days.
15. Childbirth within < 10 days.
16. Seizures at stroke onset if it precludes obtaining an accurate baseline (pr-IVT) NIHSS
17. Life expectancy (except for stroke) < 3 months.
18. Pregnancy or breastfeeding.
19. Females of childbearing potential not using effective birth control methods.
20. Known current participation in another clinical investigation with experimental drug.

E.5 End points

E.5.1

Primary end point(s)

Binary "Poor Outcome" on the mRS defined by a score of 4-6 (versus 0-3) assessed at Day 90

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 90

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint: Binary “Favorable Outcome” on the mRS defined by a score of 0-2 (versus 3-6) assessed at Day 90
Other Secondary Efficacy Endpoints:
•All-cause mortality at Day 90
• mRS 0-1
• mRS 5-6 at Day 90
•Ordinal mRS at Day 90
• Utility-Weighted mRS
•All-cause mortality within 72 hours
•Symptomatic and non-symptomatic ICHs
• Neurological Status Change as assessed by:
o Response defined by a relative decrease (%) in NIHSS value at 24 hrs compared to pre-IVT value higher than 30%.
o Relative change (%) in NIHSS value at 24 hrs compared to pre-IVT value
• Recanalization rate as centrally measured by eTICI score in those patients having a post-thrombectomy angiography with a focus on successful recanalization
• Infarct volume progression:
o Follow-up infarct volume (FIV) at 24 hrs on non-contrast CT or diffusion weighted MRI
o Infarct growth (FIV minus baseline infarct volume on non-contrast CT or diffusion-weighted MRI)
• Volume of hemorrhagic transformation
• Quality of Life, as assessed at Day 90 by the EuroQol-5 Dimensions (EQ-5D-5L)

E.5.2.1

Timepoint(s) of evaluation of this end point

T15min
6 hrs
24 hrs
7 Days
30 Days
60 Days
90 Days

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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)

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Israel

United Kingdom

United States

Belgium

Czechia

Denmark

France

Germany

Slovakia

Spain

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

E.8.9.2

In all countries concerned by the trial days

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:

133

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

267

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients experiencing an acute ischemic stroke and not conscious when
entering the study

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

350

F.4.2.2

In the whole clinical trial

400

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)

Normal standard of care

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

2022-08-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-02-02

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