Anti-MAG Neuropathy
Conditions
Keywords
peripheral neuropathy
Brief summary
In this study, the new drug called PPSGG (PN-1007) will be tested. Preliminary studies conducted in animals suggest PPSGG (PN-1007) might be a good treatment for reducing levels of anti-MAG antibodies in patients with anti-MAG neuropathy. This is the first research of PPSGG (PN-1007) in people and its main purpose is to test its safety and acceptability in patients. In this study it will be examined how the drug is changed by and removed from the body and checked for signs that the drug may be truly effective against anti-MAG neuropathy. PPSGG (PN-1007) will be tested at several different doses.
Detailed description
PPSGG (PN-1007) is intended to bind anti-MAG IgM autoantibodies, the underlying cause of anti-MAG neuropathy, in a highly selective manner, resulting in their neutralization and removal from the circulation. This allows specific targeting of anti-MAG IgM in the circulation and circumvents unspecific immunosuppression associated with current treatment strategies. This is a Phase I/IIa, First in Human (FiH), multicenter, single and multiple ascending dose escalation trial of PPSGG (PN-1007), an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies for treatment of anti-MAG neuropathy. The aim of the study is to assess the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of PPSGG (PN-1007) in a SAD and a MAD phase in an adaptive trial in anti-MAG neuropathy patients.
Interventions
DRUGPPSGG
an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies
DRUGPlacebo
A standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection
Sponsors
Polyneuron Pharmaceuticals AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The SAD phase is open label and MAD is randomized, dose escalation, double blind (patient and investigator blinded), placebo-controlled
Intervention model description
Single Group in SAD and parallel in MAD
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients 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 * Adequate hepatic and renal function
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 months. * 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 | Description |
|---|---|---|
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | 1 month | All AEs will be recorded, whether considered minor or serious, drug-related or not |
| anti-drug-antibodies ADA | 1 month in SAD | Potential ADAs (immunogenicity) resulting from exposure of patients to PPSGG (PN-1007) will be measured by ELISA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf | Day 1 to Day 42 | Area under the plasma concentration versus time curve from zero to infinity of PPSGG (PN-1007) |
| t1/2 | Day 1 to Day 42 | Terminal half life of PPSGG (PN-1007) |
| Tmax | Day 1 to Day 42 | Time of peak concentration of PPSGG (PN-1007) |
| Change From Baseline in ONLS | up to Day 150 in MAD | Overall Neuropathy Limitations Scale measures limitations in the everyday activities of the upper and lower limbs |
| Pharmacodynamic | up to Day 28 | Change in anti-MAG Buhlmann titer from baseline measured by ELISA |
| Cmax | Day 1 to Day 42 | Maximum Plasma Concentration of PPSGG (PN-1007) |
Countries
France, Netherlands, Spain, Switzerland, United Kingdom
Outcome results
None listed