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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-004822-15 | EudraCT Number |
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Randomized, double-blind, placebo-controlled Phase IIa clinical study, assessing safety, tolerability, pharmacodynamic effects and pharmacokinetics of temelimab, administered at three different dose levels (18 mg/kg or 36 mg/kg or 54 mg/kg).
In this study temelimab is administered subsequently to rituximab therapy, i.e. no co-administration of rituximab and temelimab is done in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| temelimab 18 mg/kg | Experimental | Monthly IV repeated dose |
|
| temelimab 36 mg/kg | Experimental | Monthly IV repeated dose |
|
| temelimab 54 mg/kg | Experimental | Monthly IV repeated dose |
|
| Placebo | Placebo Comparator | Monthly IV repeated dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| temelimab 18 mg/kg | Drug | temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability | Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs) | 48 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Neuroimaging | 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). | 48 weeks |
| Neuroimaging |
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Main Inclusion Criteria:
Main Exclusion Criteria:
Current diagnosis of primary progressive MS (PPMS)
Any disease other than MS (e.g. myelitis and /or bilateral optic neuritis) that could better explain the patient's signs and symptoms
Usage of any of the following medications prior to the Screening visit:
CTCAE Grade 2 or greater lymphopenia
Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study
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)
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
Pregnant or breastfeeding women
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| Name | Affiliation | Role |
|---|---|---|
| David Leppert, MD | GeNeuro Innovation SAS | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Neurology, Academic Specialist Center | Stockholm | 113 65 | Sweden |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Temelimab 18 mg/kg | Temelimab 18 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
| FG001 | Temelimab 36 mg/kg | Temelimab 36 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
| FG002 | Temelimab 54 mg/kg | Temelimab 54 mg/kg was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
| FG003 | Placebo | Placebo was given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Randomised set (RS): All patients to whom a therapeutic treatment was randomly assigned using an interactive response system. Patients were analysed in their randomisation group whatever the treatment they received
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| ID | Title | Description |
|---|---|---|
| BG000 | Temelimab 18 mg/kg | 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). |
| BG001 | Temelimab 36 mg/kg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability | Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs) | Safety set (SAF): all patients having taken at least one dose of IMP. Patients were allocated to the group based on treatment they received | Posted | Number | Participants with at least one TEAE | 48 weeks |
|
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Temelimab 18 mg/kg | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Leppert, Study director | GeNeuro SA | 225524800 | +41 | dl@geneuro.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 1, 2020 | Mar 22, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| C581064 | temelimab |
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| temelimab 36 mg/kg | Drug | 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 | Drug | temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
|
| Placebo | Drug | Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
|
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. |
| 48 weeks |
| Neuroimaging | Change in T1 and T2 lesion volume at Week 48 compared to Baseline | 48 weeks |
| Neuroimaging | 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. | 48 weeks |
| Neuroimaging | 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. | 48 weeks |
| Adverse Event |
|
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).
| BG002 | Temelimab 54 mg/kg | 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). |
| BG003 | Placebo | Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Temelimab 54 mg/kg | 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). |
| OG003 | Placebo | Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). |
|
|
| Secondary | Neuroimaging | 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). | 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. | Posted | Mean | Standard Deviation | per unit | 48 weeks |
|
|
|
|
| Secondary | Neuroimaging | 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. | PP set | Posted | Mean | Standard Deviation | per unit | 48 weeks |
|
|
|
|
| Secondary | Neuroimaging | Change in T1 and T2 lesion volume at Week 48 compared to Baseline | PP set | Posted | Mean | Standard Deviation | mL | 48 weeks |
|
|
|
|
| Secondary | Neuroimaging | 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. | Per protocol (PP) set | Posted | Median | Standard Deviation | Ratio | 48 weeks |
|
|
|
|
| Secondary | Neuroimaging | 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. | PP set | Posted | Mean | Standard Deviation | Ratio | 48 weeks |
|
|
|
|
| 0 |
| 11 |
| 1 |
| 11 |
| 10 |
| 11 |
| EG001 | Temelimab 36 mg/kg | 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). | 0 | 10 | 0 | 10 | 9 | 10 |
| EG002 | Temelimab 54 mg/kg | 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). | 0 | 10 | 0 | 10 | 10 | 10 |
| EG003 | Placebo | Monthly IV repeated dose Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total). | 0 | 10 | 1 | 10 | 9 | 10 |
| Urinary tract infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Prostatic disorder | Reproductive system and breast disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Animal bite | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Patella fracture | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypoesthesia | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Oral mucosal exfoliation | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Bacterial vaginosis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Lyme disease | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Norovirus infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Periodontitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Respiratory syncytial virus bronchiolitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Vaginal infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Difference of change from baseline a posteriori |
| Difference of change from Baseline |
| -0.021 |
| 2-Sided |
| 95 |
| -0.121 |
| 0.057 |
| Superiority |
Difference of change from Baseline a posteriori. |
| Difference of change from Baseline |
| 0.012 |
| 2-Sided |
| 95 |
| -0.036 |
| 0.059 |
| Superiority |
| Change in T2 lesion volume |
|
| ANCOVA |
| 0.7428 |
| LS Mean Difference |
| 0.01 |
| 2-Sided |
| 95 |
| -0.051 |
| 0.071 |
| Superiority |
Difference of change from Baseline a posteriori |
| Difference of change from Baseline |
| 0.005 |
| 2-Sided |
| 95 |
| -0.010 |
| 0.023 |
| Superiority |