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Clinical Trial Results:
A long-term extension of Study GNC-401 with temelimab in patients with Relapsing forms of Multiple Sclerosis (RMS) under treatment with rituximab

Summary
EudraCT number	2021-001973-21
Trial protocol	SE
Global end of trial date	30 Apr 2022

Results information
Results version number	v1(current)
This version publication date	17 Jun 2023
First version publication date	17 Jun 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GNC-402

ISRCTN number

US NCT number

NCT05049161

WHO universal trial number (UTN)

Sponsor organisation name

GeNeuro Innovation SAS

Sponsor organisation address

60A Avenue Rockfeller , Lyon, France, 69008

Public contact

Clinical Trials Information, GeNeuro Innovation SAS, +41 22552 4800, contact@geneuro.com

Scientific contact

Clinical Trials Information, GeNeuro Innovation SAS, +41 22552 4800, contact@geneuro.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

30 Apr 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

30 Apr 2022

Global end of trial reached?

Yes

Global end of trial date

30 Apr 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective is to assess the long-term 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 are treated with rituximab for at least 1 year and who participated to the clinical study GNC-401. Patients who had been on placebo in study GNC-401 were randomised to temelimab, see below for details in "Subject disposition, Recruitment".

Protection of trial subjects

All patients were to be observed for 2 hours following completion of the first three IMP infusions and for at least 1 hour following completion of the subsequent IMP infusions. Intra patient dose escalation of temelimab was not permitted.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Aug 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Sweden: 33

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Patients randomised to placebo in study GNC-401 were rerandomised to temelimab 18 mg/kg, 36 mg/kg or 54 mg/kg (1:1:1) on D1 of study GNC-402 using a web based IRS with predefined randomisation list with blocks. Patients who received temelimab in study GNC 401 continued with the same dose in study GNC-402 without the need for re-randomisation.

Screening details

Patients who met all the inclusion criteria were eligible for inclusion in the study.

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

The present study GNC-402, was performed in double-blind fashion in patients who had completed study GNC-401. At entry, all patients received active treatment with temelimab. On D1 (Baseline, Visit 1 [V1]), the patients of the placebo group in study GNC-401 were re-randomised to temelimab 18 mg/kg, 36 mg/kg or 54 mg/kg (1:1:1), while the patients who received temelimab in study GNC-401 continued with the same dose.

Are arms mutually exclusive

Yes

Temelimab 18 mg/kg

Arm description

Temelimab 18 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Temelimab

Investigational medicinal product code

GNbAC1

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Temelimab was administered by IV infusion (200 mL over 2 hours) following dilution into glucose 5% solution

Temelimab 36 mg/kg

Arm description

Temelimab 36 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Temelimab

Investigational medicinal product code

GNbAC1

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Temelimab was administered by IV infusion (200 mL over 2 hours) following dilution into glucose 5% solution

Temelimab 54 mg/kg

Arm description

Temelimab 54 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Temelimab

Investigational medicinal product code

GNbAC1

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Temelimab was administered by IV infusion (200 mL over 2 hours) following dilution into glucose 5% solution

Number of subjects in period 1	Temelimab 18 mg/kg	Temelimab 36 mg/kg	Temelimab 54 mg/kg
Started	13	11	9
Completed	13	11	9

Baseline characteristics

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Reporting group title

Temelimab 18 mg/kg

Reporting group description

Temelimab 18 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Reporting group title

Temelimab 36 mg/kg

Reporting group description

Temelimab 36 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Reporting group title

Temelimab 54 mg/kg

Reporting group description

Temelimab 54 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Reporting group values	Temelimab 18 mg/kg	Temelimab 36 mg/kg	Temelimab 54 mg/kg	Total
Number of subjects	13	11	9	33
Age categorical
Units: Subjects
Adults (18-64 years)				0
Age continuous
Units: years
arithmetic mean (standard deviation)	44.8 ( 7.3 )	44.1 ( 9.4 )	49.1 ( 4.8 )	-
Gender categorical
Units: Subjects
Female	9	5	4	18
Male	4	6	5	15

Subject analysis set title

Randomised set (RS)

Subject analysis set type

Full analysis

Subject analysis set description

All patients to whom a therapeutic treatment was randomly assigned using a web-based interactive response system. Patients were analysed in their randomisation group whatever treatment they received.

Subject analysis set title

Safety set (SAF)

Subject analysis set type

Full analysis

Subject analysis set description

All patients having taken at least one dose of IMP. Patients were allocated to the group based on the treatment they received.

Subject analysis sets values	Randomised set (RS)	Safety set (SAF)
Number of subjects	33	33
Age categorical
Units: Subjects
Adults (18-64 years)
Age continuous
Units: years
arithmetic mean (standard deviation)	45.7 ( 7.6 )	45.7 ( 7.6 )
Gender categorical
Units: Subjects
Female	18	18
Male	15	15

End points

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Reporting group title

Temelimab 18 mg/kg

Reporting group description

Temelimab 18 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Reporting group title

Temelimab 36 mg/kg

Reporting group description

Temelimab 36 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Reporting group title

Temelimab 54 mg/kg

Reporting group description

Temelimab 54 mg/kg was planned to be given by IV infusion every 4 weeks for 48 weeks

Subject analysis set title

Randomised set (RS)

Subject analysis set type

Full analysis

Subject analysis set description

All patients to whom a therapeutic treatment was randomly assigned using a web-based interactive response system. Patients were analysed in their randomisation group whatever treatment they received.

Subject analysis set title

Safety set (SAF)

Subject analysis set type

Full analysis

Subject analysis set description

All patients having taken at least one dose of IMP. Patients were allocated to the group based on the treatment they received.

Primary: Safety and Tolerability

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End point title

Safety and Tolerability ^[1]

End point description

End point type

Primary

End point timeframe

From the time the patient received their first dose of IMP until their last study visit +28 days.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistics were provided depending on the nature of considered data. This was a Phase IIa study, the primary objective being the safety. No statistical analysis was planned in the SAP for safety endpoints. Numbers and types of Adverse Events were simply described and compared across arms.

End point values	Temelimab 18 mg/kg	Temelimab 36 mg/kg	Temelimab 54 mg/kg	Safety set (SAF)
Number of subjects analysed	13	11	9	33
Units: TEAEs	7	9	7	23

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the time the patient received his/her first dose of IMP until his/her last study visit +28 days

Adverse event reporting additional description

When an AE occurred after written consent had been obtained but before the first dose of study treatment, the AE was considered a non-treatment emergent AE (also termed ‘pre treatment AE’).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Temelimab 18 mg/mL

Reporting group description

Temelimab 18 mg/mL was planned to be given as monthly (4-weekly) IV infusions for 48 weeks (12 administrations in total).

Reporting group title

Temelimab 36 mg/mL

Reporting group description

Temelimab 36 mg/mL was planned to be given as monthly (4-weekly) IV infusions for 48 weeks (12 administrations in total).

Reporting group title

Temelimab 54 mg/mL

Reporting group description

Temelimab 54 mg/mL was planned to be given as monthly (4-weekly) IV infusions for 48 weeks (12 administrations in total).

Serious adverse events	Temelimab 18 mg/mL	Temelimab 36 mg/mL	Temelimab 54 mg/mL
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 13 (0.00%)	0 / 11 (0.00%)	1 / 9 (11.11%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 13 (0.00%)	0 / 11 (0.00%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2.5%

Non-serious adverse events	Temelimab 18 mg/mL	Temelimab 36 mg/mL	Temelimab 54 mg/mL
Total subjects affected by non serious adverse events
subjects affected / exposed	7 / 13 (53.85%)	9 / 11 (81.82%)	7 / 9 (77.78%)
Investigations
Hepatic enzyme increased
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0
Limb injury
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0
Wound
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Surgical and medical procedures
Tooth extraction
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 13 (0.00%)	0 / 11 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	1
Headache
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Meralgia paraesthetica
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	2 / 9 (22.22%)
occurrences all number	0	1	2
Fatigue
subjects affected / exposed	0 / 13 (0.00%)	0 / 11 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	1 / 9 (11.11%)
occurrences all number	0	1	1
Nasal congestion
subjects affected / exposed	0 / 13 (0.00%)	0 / 11 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	1
Psychiatric disorders
Depression
subjects affected / exposed	0 / 13 (0.00%)	0 / 11 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	1
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	1 / 9 (11.11%)
occurrences all number	0	1	1
Pain in extremity
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Infections and infestations
COVID-19
subjects affected / exposed	2 / 13 (15.38%)	2 / 11 (18.18%)	4 / 9 (44.44%)
occurrences all number	1	1	1
Nasopharyngitis
subjects affected / exposed	1 / 13 (7.69%)	3 / 11 (27.27%)	3 / 9 (33.33%)
occurrences all number	1	1	1
Sinusitis
subjects affected / exposed	2 / 13 (15.38%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	1	1	0
Gastroenteritis
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Skin infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Tooth infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 11 (9.09%)	0 / 9 (0.00%)
occurrences all number	0	1	0
Urinary tract infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 11 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
30 Apr 2022	All patients were withdrawn from the study prematurely when the Sponsor decided to stop the study since temelimab was not available for clinical supply, following the worldwide shortage of culture media and supplementary reagents due to COVID-19 pandemic. The overall mean (SD) study duration was 15.0 weeks (7.6), which was similar between treatment groups. At time of termination, 33 patients were still receiving treatment with temelimab in study GNC-402 in Sweden.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A long-term extension of Study GNC-401 with temelimab in patients with Relapsing forms of Multiple Sclerosis (RMS) under treatment with rituximab

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety and Tolerability

Primary: Safety and Tolerability

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: A long-term extension of Study GNC-401 with temelimab in patients with Relapsing forms of Multiple Sclerosis (RMS) under treatment with rituximab

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety and Tolerability

Primary: Safety and Tolerability

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A long-term extension of Study GNC-401 with temelimab in patients with Relapsing forms of Multiple Sclerosis (RMS) under treatment with rituximab