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 |
Anti-MAG peripheral neuropathy is a rare disease. It occurs when the body’s own immune system develops antibodies against myelin (protein of the nerves, myelin-associated glycoprotein, MAG). |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066137 |
E.1.2 | Term | Anti-MAG neuropathy |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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E.2.2 | Secondary objectives of the trial |
pharmacokinetics of PPSGG after single and multiple intravenous administrations, pharmacodynamics, preliminary efficacy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age between 18 and 80 years, male and female. • Patient with a confirmed diagnosis of monoclonal IgM associated with monoclonal gammopathy of undetermined significance (MGUS) with anti-MAG activity (titer of > 10’000 Bühlmann Titer units (BTU) and demyelinating neuropathy defined by electrophysiological criteria according to European Federation of Neurological Societies/Peripheral Nervous System paraproteinemic demyelinating neuropathy EFNS/PNS PDN guideline, 2010. • Clear clinical signs of disability: with at least ONLS ≥ 2 in lower extremities. • Inflammatory Neuropathy Cause and Treatment sensory sum score (ISS) ≥2. • Adequate hepatic and renal function
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E.4 | Principal exclusion criteria |
• Patients with total serum IgM levels >30 g. • Hematological malignancy, prior malignancy of any organ system (except BCC) • Previous immunosuppressive treatment with intravenous immunoglobulin (IVIG) or apheresis/plasmapheresis in the preceeding 3 months, and cyclophosphamide and/or biologicals (e.g. rituximab): in the preceeding 6 months prior to enrolment • Other neurological, neuromuscular, rheumatologic or orthopedic conditions with significant impact on the capability of walking preventing evaluation of neurological scores
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of safety based on vital signs, physical examination, ECGs, laboratory assessments, Signs of infusion-related reactions, including clinical signs and symptoms, changes in diastolic or systolic blood pressure, heart rate, oxygen saturation, and skin reactions or local reactions at the infusion site and collection of AEs assessed from baseline until the end of the study visit. Presence of anti-drug antibodies (ADA) will also be investigated |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ECG: 1-lead during infusions, 12-lead predose, 1h, 2h, 8h post dose and EOS during SAD and during MAD on infusion days (Day 1-7, 8, 14, 21, 28, 35, 42, 56), 70, 98, EOS. The same days for vital signs Safety lab: SAD: SCR, baseline, Day 8, EOS Safety lab: MAD: SCR, baseline, Day 8, 28, 42, 98, EOS. |
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E.5.2 | Secondary end point(s) |
PK: Non-compartmental parameters related to PPSGG, including but not limited to Tmax, Cmax, as well as trough (pre-dose) levels after multiple dose, PD: Reduction of anti-MAG antibodies (Anti-MAG IgM Titers (BTU), Paraprotein levels (g/l) and total IgM (g/L) Time to anti-MAG IgM rebound (time until antibody levels are reach individual pre-treatment /baseline levels again), Paraprotein levels (g/L), Total IgM levels (g/L), Anti-human natural killer-1 (HNK-1) titers, preliminary efficacy: Change in ONLS score, Time to walk 10 meters, RODS, Ataxia score, Modified ISS, exploratory endpoint and in selected sites only), Grip Strength |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK during infusion day in SAD and in MAD only on infusion days 1, 3, 5, 42: 30, 60min, 2, 6, 8 h. PK and PD on Day 1, 2, 4, 8, 14 and EoS during SAD and on Day 1-5,8,14,21,28,35,42,56,70, EOS and FU during MAD Scores: for SAD: SCR, D14, EOS and Day 42 (FU) for MAD: SCR, Day 14, 42, 98, EOS and 180 |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
During SAD open non controlled and during MAD placebo controlled, randomised |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
France |
Netherlands |
Spain |
Switzerland |
United Kingdom |
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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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Study Completion (SC) is defined as when the last patient completes their EOS visit at the end of the MAD phase, or at the end of SAD, if the patient decides not to continue with the MAD, and any repeated assessments associated with this visit have been followed-up appropriately by the investigator, or in the event of an early study termination decision, the date of that decision. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |