| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| relapsing multiple sclerosis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsing-remitting (RR) multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and axonal loss. |
|
| 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 | 18.1 |
| 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 |
|
| 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 |
| To investigate the ability of the HAP score to accurately predict responders to Octagam 5% |
|
| E.2.2 | Secondary objectives of the trial |
| • To verify that Octagam 5% in predicted responders is of at least similar effectiveness as the first-line therapies IFN-β sc or GA • To verify that the HAP score result is of no predictive power for the ARR in IFN-β sc or GA treated patients • To evaluate the assumption that the HAP score truly predicts the effectiveness of treatment with Octagam 5% and not the progress of disease as such • To investigate the proportion of patients responding to IMP treatment vs. patients not responding • To investigate the effect of IMP treatment on the time to first medically confirmed relapse after 3-month run-in phase • To investigate the effect of IMP treatment on the level of disability, evaluated by means of the EDSS and the MSFC score • To investigate the effect of IMP treatment on the brain by means of MRI parameters (lesion number and volume; whole brain volume) • To investigate the effect of IMP treatment on health-related QoL • To investigate the safety and tolerability of IMP treatment |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Patients aged ≥18 years and ≤65 years
2) Early diagnosed relapsing form of MS (≤ 5years) according to the revised McDonald criteria (1-3)
3) Patients who are at least 3 months on stable dosage of either IFN-β sc or GA and who did NOT receive the other first-line therapy before, OR patients who are treatment-naïve
4) Kurtzke’s EDSS ≤3.5
5) Patients who experienced at least one medically confirmed relapse during the last 12 months or at least two such relapses in the last 24 months prior to study entry (but not within 30 days between last steroid treatment of relapse and start of screening;
subjects who relapse during the screening phase can be re-screened, once the relapse has resolved but earliest 30 days after the end of relapse treatment with steroids) or at least 1 T1 Gd+ lesion at screening
6) Voluntarily given, fully informed written consent obtained from patient before any study-related procedures are conducted
7) Patient must be capable to understand and comply with the relevant aspects of the study protocol. |
|
| E.4 | Principal exclusion criteria |
1) Patients who have received treatment with immunoglobulins for any reason in the last 6 months
2) Patients who have received immunosuppressive treatments such as azathioprine, mitoxantrone, cyclophosphamide, teriflunomide or fingolimod in the last 6 months
3) Patients who have received rituximab or other immune cell depleting therapies in the last 18 months
4) Treatment with steroids (oral or parenteral, long-term, i.e. 30 days or more, not intermittent or burst, daily, ≥0.15 mg of prednisone or equivalent/kg/day ) except relapse treatment with corticosteroids
5) Patients who have received monoclonal antibody therapy with natalizumab in the last 12 months
6) Patients who have ever received monoclonal antibody therapies with alemtuzumab, daclizumab, or ocrelizumab
7) Patients with renal function impairment as defined by estimated glomerular filtration rate (eGFR) ≤60 mL/min
8) Patients with known intolerance to homologous immunoglobulins, especially immunoglobulin A (IgA) deficiency, when the patient has antibodies against IgA
9) Patients with a history of deep vein thrombosis or thrombotic complications of IVIG therapy
10) Patients with a body weight of ≥120 kg
11) Patients with a history of anaphylaxis after previous transfusions of blood or blood products
12) Patients for whom MRI is contraindicated or who are allergic to gadolinium
13)Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to use an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or
vasectomised partner) while on study
14) Patients with a diagnosis of significant depression or medical history of suicide attempts
15) Patients with known chronic infectious diseases (e.g. hepatitis B or C, HIV, syphilis, tuberculosis) or malignant disease
16) Patients with known antibody deficiencies or other autoimmune diseases other than MS
17) Patients with medical history of epilepsy
18) Patients with decompensated liver disease
19) Patients participating in another study during the course of this study or during the past 3 months or who have ever participated in a study investigating new diseasemodifying or immunosuppressive drugs
20) Patients who are institutionalised or kept in detention. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Superiority with regard to decreased ARR of Octagam 5% treatment in patients pre-classified as predicted responders (“RO”) compared to predicted nonresponders (“NRO”) to Octagam 5% treatment |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints are:
• ARR of Octagam 5% treatment compared to active control (first-line therapy: IFN-β sc or GA)
• ARR of IFN-β sc or GA treatment compared between predicted responders (“RI/G”) and non-responders (“NRI/G”) to Octagam 5% treatment
• Compare ARR of “RO” with both IMP treatment arms combined (“RI/G” and “NRI/G”)
• Percentage of responders and non-responders in the 21-month period between 3 months after first study treatment administration (“run-in” phase) and the end of treatment period at month 24)
• Time from randomisation to first medically confirmed relapse after 3-month run-in phase
• Time from last relapse before enrolment to first medically confirmed relapse after 3-month run-in phase
• Progression of the disease (defined as an increase of the EDSS), confirmed at 2 separate assessments at least 12 weeks apart
• Change in MSFC
• Cerebral MRI assessments: number and volumes of Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) enhancing lesions with T1 weighted imaging; number of new and enlarging T2 lesions; number of new T1 Black Holes; volumes of T1 and T2 lesions; whole brain volume
• Health-related Quality of Life assessed by MSQOL-54
Secondary safety endpoints are:
• Adverse event (AE) monitoring
• Vital signs (blood pressure, heart rate, body temperature and respiratory rate)
• Standard laboratory safety tests (clinical chemistry and haematology) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 29 |
| 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 |
| Austria |
| Bulgaria |
| Germany |
| Hungary |
| Poland |
| Russian Federation |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| 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 | 4 |
| 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 |
Print
