First in human study to test the safety and preliminary efficacy of PPSGG, an antibody catcher in patients with anti-MAG neuropathy

Phase 1

Conditions: anti-MAG neuropathy
MedDRA version: 21.1Level: LLTClassification code 10066137Term: Anti-MAG neuropathySystem Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-000067-23-GB

Lead Sponsor: Polyneuron Pharmaceuticals AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 48

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

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

•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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 (ADA) 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 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<br>Safety lab: SAD: SCR, baseline, Day 8, EOS<br>Safety lab: MAD: SCR, baseline, Day 8, 28, 42, 98, EOS.

Secondary Outcome Measures

Name	Time	Method
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;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. <br>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<br>Scores: for SAD: SCR, D14, EOS and Day 42 (FU)<br>for MAD: SCR, Day 14, 42, 98, EOS and 180

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