Trial Outcomes & Findings for Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (NCT NCT04480307)

NCT ID: NCT04480307

Last Updated: 2024-11-07

Results Overview

Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

48 weeks

Results posted on

2024-11-07

Participant Flow

Screening details: Subjects who met the inclusion criteria at the Screening visit (within 3 weeks prior to dosing) and at the Baseline visit (Study Day 1 (SD1)) were considered eligible to participate in the clinical study.

Participant milestones

Participant milestones
Measure	Temelimab 18 mg/kg Temelimab 18 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg Temelimab 36 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg Temelimab 54 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo Placebo was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Overall Study STARTED	11	10	10	10
Overall Study COMPLETED	11	9	10	9
Overall Study NOT COMPLETED	0	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Temelimab 18 mg/kg Temelimab 18 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg Temelimab 36 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg Temelimab 54 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo Placebo was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Overall Study Withdrawal by Subject	0	1	0	0
Overall Study Adverse Event	0	0	0	1

Baseline Characteristics

Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temelimab 18 mg/kg n=11 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=10 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=10 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=10 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	41 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	43.2 years STANDARD_DEVIATION 7.3 • n=5 Participants	47.9 years STANDARD_DEVIATION 6.3 • n=7 Participants	45.2 years STANDARD_DEVIATION 10.2 • n=5 Participants	45.6 years STANDARD_DEVIATION 9.4 • n=4 Participants	45.4 years STANDARD_DEVIATION 8.3 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	21 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	4 Participants n=4 Participants	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	39 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment Sweden	11 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	41 participants n=21 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: Safety set (SAF): all patients having taken at least one dose of IMP. Patients were allocated to the group based on treatment they received

Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs)

Outcome measures

Outcome measures
Measure	Temelimab 18 mg/kg n=11 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=10 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=10 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=10 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Safety and Tolerability	10 Participants with at least one TEAE	9 Participants with at least one TEAE	10 Participants with at least one TEAE	9 Participants with at least one TEAE

SECONDARY outcome

Timeframe: 48 weeks

Population: Per protocol (PP) set: All patients of the RS with no major protocol deviations and with at least 9 infusions performed. All protocol deviations were assessed and documented on a case-by-case basis prior to database lock, and deviations considered to have a serious impact on the efficacy results led to the relevant patient being excluded from the set.

Change in magnetization transfer saturation (MT Sat) in periventricular NAWM at Week 48 compared to Baseline. The MT Sat represents the fraction of free water, as transformed to per-unit scale, saturated by a single Magnetization transfer (MT) pulse during repetition time (TR).

Outcome measures

Outcome measures
Measure	Temelimab 18 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=7 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=8 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Neuroimaging	-0.011 per unit Standard Deviation 0.097	-0.060 per unit Standard Deviation 0.081	-0.016 per unit Standard Deviation 0.194	0.008 per unit Standard Deviation 0.113

SECONDARY outcome

Timeframe: 48 weeks

Population: PP set

Change in magnetization transfer saturation (MT Sat) in cortex at Week 48 compared to Baseline. The MT Sat represents the fraction of free water, as transformed to per-unit scale, saturated by a single Magnetization transfer pulse during repetition time.

Outcome measures

Outcome measures
Measure	Temelimab 18 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=6 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=7 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Neuroimaging	0.037 per unit Standard Deviation 0.058	0.044 per unit Standard Deviation 0.044	-0.013 per unit Standard Deviation 0.077	0.018 per unit Standard Deviation 0.040

SECONDARY outcome

Timeframe: 48 weeks

Population: PP set

Change in T1 and T2 lesion volume at Week 48 compared to Baseline

Outcome measures

Outcome measures
Measure	Temelimab 18 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=9 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=8 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Neuroimaging Change in T1 lesion volume	-0.055 mL Standard Deviation 0.315	-0.032 mL Standard Deviation 0.686	0.227 mL Standard Deviation 0.405	-0.044 mL Standard Deviation 0.185
Neuroimaging Change in T2 lesion volume	0.028 mL Standard Deviation 0.085	0.029 mL Standard Deviation 0.088	0.023 mL Standard Deviation 0.061	0.027 mL Standard Deviation 0.075

SECONDARY outcome

Timeframe: 48 weeks

Population: Per protocol (PP) set

Change in brain parenchymal volume fraction at Week 48 compared to Baseline. The brain parenchymal fraction is defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour.

Outcome measures

Outcome measures
Measure	Temelimab 18 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=9 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=8 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Neuroimaging	-0.013 Ratio Standard Deviation 0.011	-0.021 Ratio Standard Deviation 0.032	-0.011 Ratio Standard Deviation 0.013	-0.019 Ratio Standard Deviation 0.017

SECONDARY outcome

Timeframe: 48 weeks

Population: PP set

Change in thalamic volume fraction at Week 48 compared to Baseline. The thalamic volume fraction is the ratio of the legitimate (i.e. thalamic) brain tissue volume to the total volume within the brain surface contour.

Outcome measures

Outcome measures
Measure	Temelimab 18 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=9 Participants Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=9 Participants Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=8 Participants Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Neuroimaging	-0.000 Ratio Standard Deviation 0.000	-0.000 Ratio Standard Deviation 0.000	-0.000 Ratio Standard Deviation 0.000	-0.000 Ratio Standard Deviation 0.000

Adverse Events

Temelimab 18 mg/kg

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Temelimab 36 mg/kg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Temelimab 54 mg/kg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Temelimab 18 mg/kg n=11 participants at risk Monthly IV repeated dose Temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 36 mg/kg n=10 participants at risk Monthly IV repeated dose Temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Temelimab 54 mg/kg n=10 participants at risk Monthly IV repeated dose temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).	Placebo n=10 participants at risk Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
Infections and infestations COVID-19	9.1% 1/11 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).	0.00% 0/10 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).	0.00% 0/10 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).	0.00% 0/10 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).
Infections and infestations Urinary tract infection	0.00% 0/11 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).	0.00% 0/10 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).	0.00% 0/10 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).	10.0% 1/10 • The collection of Adverse Events (AEs) was from the time the patient signed the informed consent onwards up to Week 48. Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs).

Other adverse events

Additional Information

David Leppert, Study director

GeNeuro SA

Phone: 225524800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place