Clinical Trials Register

Summary
EudraCT Number:	2019-004822-15
Sponsor's Protocol Code Number:	GNC-401
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-01-17
Trial results	View 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

Sweden - MPA

A.2

EudraCT number

2019-004822-15

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo Controlled Trial, Examining the Safety, Tolerability, Pharmacodynamic Effects and Pharmacokinetics of Temelimab Following Rituximab Treatment in Patients with Relapsing Forms of Multiple Sclerosis (RMS)

A.3.1

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

A Clinical Trial Examining the Effects of Temelimab Following Rituximab Treatment in Patients with Multiple Sclerosis

A.3.2

Name or abbreviated title of the trial where available

ProTEct-MS

A.4.1

Sponsor's protocol code number

GNC-401

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	GeNeuro Innovation SAS
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	GeNeuro Innovation SAS
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	GeNeuro Innovation SAS
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	60 avenue Rockefeller
B.5.3.2	Town/ city	Lyon
B.5.3.3	Post code	69008
B.5.3.4	Country	France
B.5.4	Telephone number	+4122552 4800
B.5.6	E-mail	contact@geneuro.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	Temelimab
D.3.2	Product code	GNbAC1
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	temelimab
D.3.9.1	CAS number	1393641-34-3
D.3.9.2	Current sponsor code	GNbAC1
D.3.9.4	EV Substance Code	SUB174388
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	16.7
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.IMP: 2
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	Temelimab
D.3.2	Product code	GNbAC1
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	temelimab
D.3.9.1	CAS number	1393641-34-3
D.3.9.2	Current sponsor code	GNbAC1
D.3.9.4	EV Substance Code	SUB174388
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	33.3
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.IMP: 3
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	Temelimab
D.3.2	Product code	GNbAC1
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	temelimab
D.3.9.1	CAS number	1393641-34-3
D.3.9.2	Current sponsor code	GNbAC1
D.3.9.4	EV Substance Code	SUB174388
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	50
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 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

Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

Multiple Sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10080700
E.1.2	Term	Relapsing multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 assess the safety and tolerability of temelimab following intravenous (IV) administration of 18 mg/kg, 36 mg/kg or 54 mg/kg, in patients with RMS who have been treated with rituximab for at least 1 year

E.2.2

Secondary objectives of the trial

To determine the pharmacodynamic effects of temelimab on neuroprotection and remyelination based on neuroimaging .

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The subject has given written informed consent to participate in the study
2. Current diagnosis of RMS, based on the McDonald 2017 criteria
3. Having received treatment with rituximab, as per local clinical routine for at least 12 months prior to the Screening Visit
4. Having received their last dose of rituximab not more than 8 weeks and not less than 4 weeks before Randomization (Study Day 1)
5. Having B-cell count < Lower limit of detection (LLOD) (<0.01*10-9 CD19+ cells/ L)
6. Having expanded disability status scale (EDSS) 2.5 – 5.5 inclusive at Baseline
7. Present clinical worsening in one or more neurological domains as assessed by EDSS, ambulatory function as assessed by 6MWT or T25FW, cognitive functioning as assessed by SDMT or increased need of walking aids or pharmacological/procedures for bowel and bladder functions over the last year.
8. Brain Magnetic resonance imaging (MRI), lesion burden with >9 T2 cerebral lesions (assessed within the last 24 months)
9. Stable clinical presentation of MS for 30 days prior to Screening e.g. no relapse, no acute neurological exacerbation.
10. Age range from 18 to 55 years (both inclusive)
11. Body weight between 40 – 100 kg (both ranges are inclusive)
12. No disease modifying therapies (DMTs) other than rituximab, within 12 months of Screening
13. No contraindication to Biomarker assessments: brain Magnetic resonance imaging (MRI), blood/serum collection and cerebrospinal fluid (CSF) collection
14. Agreeing to undergo two lumbar puncture
15. Be willing and able to follow all study procedures and assessments according to the study protocol
16. Female patients of childbearing potential (FPCBP) or procreative male patients (PMP), willing to use highly effective contraceptive methods throughout the study duration and at least until 5 months after the last study treatment

E.4

Principal exclusion criteria

1. Current diagnosis of primary progressive MS (PPMS)
2. Any disease other than MS (e.g. myelitis and /or bilateral optic neuritis) that could better explain the patient’s signs and symptoms
3. Usage of any of the following medications prior to the Screening visit:
a) Any usage of interferon beta, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide within 12 months prior to Screening,
b) Any history of exposure to mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation at any time,
c) Any usage of natalizumab within 24 months prior to Screening,
d) Any usage of highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine within 12 months prior to Screening,
e) Any usage of any experimental treatment if not washed out for ≥ 5 half-lives or ≥ 12 months (whichever is longer), except rituximab which is allowed before the study.
4. CTCAE Grade 2 or greater lymphopenia
5. Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including:
a) Diagnosis or history of schizophrenia
b) Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation
c) Current or past (within the last 2 years) alcohol or drug abuse
6. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (NYHA class 3 or 4)
7. Known inability to undergo an MRI scan
8. Contraindications to the use of glucose 5% infusion
9. Inability to follow study instructions, or complete study assessments, as defined by the protocol
10. Any history of cancer with the exceptions of basal cell carcinoma and/or carcinoma in situ of the cervix, and only if successfully treated by complete surgical resection, with documented clean margins and any medically unstable condition as determined by the investigator
11. Legal incapacity or limited legal capacity
12. Pregnant or breastfeeding women
13. History of, or positive serology for viral hepatitis B not explained by vaccination
14. History of, or positive serology for viral hepatitis C or human immunodeficiency virus (HIV) at any time
15. Abnormal liver function tests: AST or ALT > 2 times upper limit of normal range (ULN), or conjugated bilirubin > 2 times ULN, or AP or GGT > 3 times ULN
16. Positive pregnancy test at any time

E.5 End points

E.5.1

Primary end point(s)

• Overall Summary of Adverse Events
• AEs by Primary SOC and PT
• SAE by Primary SOC and PT
• Physical Examination: Shift from Baseline to worst post-dose result by Body System
• ECG Interpretation: Change from Baseline to Week 48 and Summary Statistics for change from Baseline to Week 48
• Vital Signs: Summary Statistics For Change From Baseline By Follow-Up Visit
• Concomitant Medications by WHO ATC Level Class 1 and WHO ATC Level Class 2
• Hematology: Normal Range Shifts from Baseline by Follow-Up visit
• Clinical Chemistry (including C-reactive protein): Normal Range Shifts from Baseline by Follow-Up Visit -Safety Set
• Coagulation: Normal Range Shifts from Baseline by Follow-Up Visit -Safety Set
• Urinalysis: Normal Range Shifts from Baseline by Follow-Up Visit

E.5.1.1

Timepoint(s) of evaluation of this end point

Over 48 weeks

E.5.2

Secondary end point(s)

• Change in magnetization transfer (MTR) in periventricular normal-appearing white matter (NAWM) at week 48 compared to baseline
• Change in magnetization transfer (MTR) in cerebral cortex at week 48 compared to baseline
• Change in T1 lesion volume at week 48 compared to baseline
• Change in T2 lesion volume at week 48 compared to baseline
• Change in brain parenchymal volume fraction at week 48 compared to baseline
• Change in thalamic volume fraction at week 48 compared to baseline

E.5.2.1

Timepoint(s) of evaluation of this end point

at week 48

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

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

Yes

E.6.13.1

Other scope of the trial description

Quality of Life assessments, Immunogenicity, Biomarkers

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)

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

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:

F.1.3

Elderly (>=65 years)

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.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)

None

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

2020-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-01-24

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