anti-MAG neuropathy MedDRA version: 21.1 Level: LLT Classification code 10066137 Term: Anti-MAG neuropathy System Organ Class: 100000004852
Conditions
Sponsors
Polyneuron Pharmaceuticals AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age between 18 and 80 years, male and female. • Patient with a confirmed diagnosis of monoclonal IgM associated with MGUS with anti-MAG activity (titer of > 10’000 BTU) and demyelinating neuropathy defined by electrophysiological criteria according to EFNS/PNS PDN guideline, 2010. • Clear clinical signs of disability: with at least ONLS = 2 in lower extremities. • Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score =2. • Adequate hepatic and renal function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: • Patients with total serum IgM levels >30 g. • Hematological malignancy, prior malignancy of any organ system (except BCC) • Prior immunosuppression: No IVIG in previous 3 months, no previous cyclophosphamide or biologicals in prior 6/12. • Other neurological, neuromuscular, rheumatologic or orthopedic condition with significant impact on the capabilities of walk preventing evaluation of neurological scores
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: safety and tolerability ;Secondary Objective: pharmacokinetics of PPSGG after single and multiple intravenous administrations, pharmacodynamics, preliminary efficacy;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 will also be investigated;Timepoint(s) of evaluation of this end point: ECG: 1-lead during infusions, 12-lead predose, 1h, 2h, 8h post dose. On Day 2 and EOS during SAD and during MAD on infusion days (Day 1-5, 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 and time to reduction, Time to anti-MAG IgM rebound (to pre-treatment BTU levels), Paraprotein levels (g/L), Total IgM levels (g/L), Anti-human natural killer-1 (HNK-1) IgM titers, Reduction of anti-MAG antibodies by =50% and time to reduction, preliminary efficacy: Change in ONLS score, Time to walk 10 meters, RODS, Ataxia score, Modified ISS, MUNIX (motor unit number index), Grip Strength;Timepoint(s) of evaluation of this end point: PK during infusion: 5, 30, 60min, 2, 6, 8 h, PK and PD on SCR, baseline, Day 2, 4, 8 and 14 during SAD and on Day 1-5,8,14,21,28,35,42,56,70, EOS and FU during MAD Scores: SCR, Day 14, 42, 98, EOS and 180 during MAD | — |
Countries
France, Netherlands, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinical Trial Helpdesk
Polyneuron Pharmaceuticals
Outcome results
None listed