Clinical Trials Register

Summary
EudraCT Number:	2021-002148-56
Sponsor's Protocol Code Number:	ACT-CS-005
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-11-16
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

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

RANDOMIZOVANÉ, DVOJITĚ ZASLEPENÉ, MULTICENTRICKÉ, MULTINÁRODNÍ, PLACEBEM KONTROLOVANÉ, PARALELNĚ USPOŘÁDANÉ, ADAPTIVNÍ KLINICKÉ HODNOCENÍ S PODÁNÍM JEDNÉ DÁVKY, ZKOUMAJÍCÍ ÚČINNOST A BEZPEČNOST GLENZOCIMABU JAKO PŘÍDATNÉ LÉČBY NAVÍC KE STANDARDNÍ LÉČBĚ V PRŮBĚHU 4,5 HODINY PO AKUTNÍ ISCHEMICKÉ CÉVNÍ MOZKOVÉ PŘÍHODĚ

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.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	HOPITAL COCHIN 27 RUE DU FAUBOURG SAINT JACQUES
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

Primary Objective:
• To show the efficacy of glenzocimab vs. placebo, on at least one of the 2 dual endpoints, i.e. the ordinal modified Rankin Scale (mRS) assessed at Day 90 or the binary poor outcome defined as a mRS score of 4-6 assessed at Day 90, either in the overall population (denoted as OP) or in the subgroup of patients who received Mechanical Thrombectomy (denoted as MT+).

E.2.2

Secondary objectives of the trial

Key Secondary Objectives:
• To show the efficacy of glenzocimab vs. placebo on the all-cause mortality at day-90 either in the OP or in the subgroup of patients who received MT+.
Other Secondary Objectives:
Efficacy:
• To assess the favorable responses defined as mRS score of 0-1
•To assess the good responses defined as mRS score 0-2
•To assess the utility weighted mRS (UW-mRS)
•To assess the evolution of the National Institute of Health Stroke Scale (NIHSS) score
•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)
Safety:
•To assess the number of the following events:
o Symptomatic and non-symptomatic intracranial hemorrhages, o Deaths, o Serious adverse events (SAEs), 3 more are in the Protocol Synopsis

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
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 ≥ 4
5. In whom thrombolysis with rt-PA is or has been initiated, whether
or not patients are additionally eligible to mechanical thrombectomy
(MT + alteplase).
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 sal pingectomy 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 should 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 device (IUD),
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.

E.4

Principal exclusion criteria

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

E.5 End points

E.5.1

Primary end point(s)

Primary Dual Endpoint:
Ordinal modified Ranking Scale at Day 90

E.5.1.1

Timepoint(s) of evaluation of this end point

Ordinal mRS assessed at Day 90

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint:
All-Cause Mortality at Day 90
Other Secondary Efficacy Endpoints:
•mRS 0-1
•mRS 0-2
•Utility-Weighted mRS
•Neurological Status Change as assessed by:
-Response defined by a relative decrease (%) in NIHSS value at 24 hrs compared to pre-IVT value higher than 30%.
-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:
-Follow-up infarct volume (FIV) at 24 hrs on non-contrast CT or diffusion weighted MRI
-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)
SAFETY Secondary Endpoints:
Incidence of the following events:
•Deaths within the first 24 hrs and over the whole study period until Day 90 (Kaplan-Meier curve)
•Symptomatic intracranial hemorrhages, defined by both anatomical imaging (according to Heidelberg's classification) AND an increase in NIHSS score by 4 points or greater, or death that is not explained otherwise (according to ECASS III study definition (9))
•Non-symptomatic hemorrhages, seen on 24 hrs plain
CT-Scan or MRI, not present at baseline assessment, once other diagnoses are excluded
•ncidence, nature and severity of Adverse Events, SAEs, bleeding-related events (BREs), and Treatment-Emergent Adverse Events (TEAEs)
•Change in Blood Pressure, Heart Rate at any visit until Discharge/Day 7 as compared to Baseline
•Change in clinical laboratory assessments (hematology, biochemistry) at 24 hrs and Discharge/Day 7 as compared to Baseline
•Change in coagulation parameters (INR, PT, aPTT) at 24 hrs as compared to Baseline
•ECG changes at 24 hrs and Discharge/Day 7 as compared to Baseline.

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 States

Belgium

Czechia

Denmark

France

Germany

Slovakia

Spain

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

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:

333

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

667

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

750

F.4.2.2

In the whole clinical trial

1000

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

2022-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-09

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials