E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the long term safety of GNbAC1 in patients with RRMS. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the long-term efficacy of GNbAC1 in terms of MRI outcomes, relapse rate, disability and disease progression. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients must have completed Period 2 of study GNC-003 and must meet all eligibility criteria for the GNC-004 study;
- Patients (male or female with reproductive potential) must agree to use highly effective methods of birth control |
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E.4 | Principal exclusion criteria |
- Patients not having completed study GNC-003.
- Emergence of any disease diagnosis during the course of study GNC-003 that is not MS and could better explain the patient’s neurological signs and symptoms.
- Any major medical or psychiatric disorder that could put the patient at undue risk during the study, according to the investigator’s opinion, or that would affect the capacity of the patient to fulfill the requirements of the study, including: Schizophrenia, bipolar disorder, or major depressive disorder, History of suicide attempt, or current suicidal ideation, current alcohol or drug abuse.
- Body weight<40kg
- Patients not able to follow study instructions, or not able to follow the study assessments defined by the protocol.
- Forbidden concomitant treatments
- Legal incapacity or limited legal capacity.
- Pregnancy.
- Female patients of childbearing potential (FPCBP) or procreative male patients (PMP), not willing to use highly effective contraceptive methods throughout the study duration and at least until 5 months after the last study treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following parameters will be evaluated to assess the long term safety of GNbAC1:
- Spontaneously-reported adverse events (AEs) and serious adverse events (SAEs);
- Clinical safety laboratory (Haematology, Chemistry, Coagulation), urinalysis and pregnancy urinary test;
- IgG4 dosing;
- Physical examination and vital signs: Blood pressure, heart rate, temperature, and body weight;
- 12-lead ECG;
- Human anti-GNbAC1 antibodies in serum;
- Suicidality assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- AEs at each visit; SAEs at any time
-Laboratory parameters and urinalysis every 6 months and urine pregnancy test at each study visit
- Physical examination and vital signs at selection and at each study visit
- C-SSRS at every visit
- ECG and human anti-GNbAC1 antibodies every 6 months
- IgG4 at baseline, W48 and W96 |
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E.5.2 | Secondary end point(s) |
The following parameters will be evaluated to assess the long term efficacy of GNbAC1:
- Brain MRI markers of inflammation, disease progression, demyelination and remyelination;
- Annualized relapse rate;
- Proportion of patients with confirmed neurological disability worsening (defined as an increase of ≥ 1.5 step on the EDSS for EDSS= 0; increase of ≥ 1 step on the EDSS from EDSS > 0 and < 5.5; and ≥0.5 EDSS steps from EDSS ≥ 5.5, confirmed after at least 3 months at scheduled clinic visits)
- Proportion of patients with confirmed neurological disability improvement (defined as a decrease of at least 1 step on the EDSS from EDSS ≥1 and < 5.5and decrease of at least 0.5 EDSS steps from EDSS ≥ 5.5, confirmed after at least 3 months at scheduled clinic visits)
- Proportion of patients with No Evidence of Disease Activity (NEDA, defined as absence of new T1 or T2 lesions on MRI scan, absence of relapse and absence of confirmed disability worsening at Week 48 and 96);
- Time to confirmed neurological disability worsening (as defined above);
- Time to confirmed neurological disability improvement (as defined above);
- Mean change in EDSS Step from baseline in GNC-003 study;
- Mean change in MSFC scores (including subcomponent scores) from baseline in GNC-003 study. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Brain MRI at Weeks 48 and 96
- Annualized relapse rate at Weeks 48 and 96
- EDSS and MSFC at Weeks 24, 48, 72 and 96
- Proportion of patients with confirmed neurological disability worsening or improvement from baseline in GNC-003 study to weeks 24, 48, 72 and 96 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, biomarkers analysis |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | No |
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 |
Bulgaria |
Croatia |
Czech Republic |
Estonia |
Germany |
Hungary |
Italy |
Poland |
Russian Federation |
Serbia |
Spain |
Ukraine |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |