First in Human Study to Test the Safety and Preliminary Efficacy of PPSGG in Patients With Anti-MAG Neuropathy

Study Overview
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Brief Summary
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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
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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.

Official Title
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First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of PPSGG (PN-1007) in Anti-MAG Neuropathy Patients

Conditions
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Anti-MAG Neuropathy

Intervention / Treatment
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* Drug: PPSGG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single Group in SAD and parallel in MAD
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PPSGG<br>sterile liquid, one 1-hour infusion in SAD and multiple infusions in MAD. In SAD multiple cohorts being tested. Dosage and regime in MAD to be defined based on SAD outcome. | Drug: PPSGG<br>* an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies<br>* Other names: PN-1007;|
| Placebo Comparator: Placebo<br>standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection | Drug: Placebo<br>* A standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | All AEs will be recorded, whether considered minor or serious, drug-related or not | 1 month | 
| anti-drug-antibodies ADA | Potential ADAs (immunogenicity) resulting from exposure of patients to PPSGG (PN-1007) will be measured by ELISA | 1 month in SAD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time of peak concentration of PPSGG (PN-1007) | Day 1 to Day 42 | 
| Cmax | Maximum Plasma Concentration of PPSGG (PN-1007) | Day 1 to Day 42 | 
| AUCinf | Area under the plasma concentration versus time curve from zero to infinity of PPSGG (PN-1007) | Day 1 to Day 42 | 
| t1/2 | Terminal half life of PPSGG (PN-1007) | Day 1 to Day 42 | 
| Pharmacodynamic | Change in anti-MAG Buhlmann titer from baseline measured by ELISA | up to Day 28 | 
| Change From Baseline in ONLS | Overall Neuropathy Limitations Scale measures limitations in the everyday activities of the upper and lower limbs | up to Day 150 in MAD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral neuropathy