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

Phase 1

Terminated

• Conditions: Anti-MAG Neuropathy
• Interventions: Drug: PPSGG; Drug: Placebo

• Registration Number: NCT04568174
• Lead Sponsor: Polyneuron Pharmaceuticals AG

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.

Study Timeline

• Study First Submitted: 2020-09-08
• Study First Submitted QC: 2020-09-23
• Study First Posted: 2020-09-29
• Study Start: 2020-11-17
• Primary Completion: 2021-09-23
• Study Completion: 2021-09-23
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-07
• Last Update Posted: 2021-10-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PPSGG	PPSGG	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.
Placebo	Placebo	standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection

Primary Outcome Measures

Name	Time	Method
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
Adverse Events (AEs) and Serious Adverse Events (SAEs)	1 month	All AEs will be recorded, whether considered minor or serious, drug-related or not

Secondary Outcome Measures

Name	Time	Method
Tmax	Day 1 to Day 42	Time of peak concentration of PPSGG (PN-1007)
Cmax	Day 1 to Day 42	Maximum Plasma Concentration of PPSGG (PN-1007)
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)
Pharmacodynamic	up to Day 28	Change in anti-MAG Buhlmann titer from baseline measured by ELISA
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

Trial Locations

Locations (7)

Lausanne; 🇨🇭 Lausanne, Switzerland

Barcelona; 🇪🇸 Barcelona, Spain

Service de Neurologie Centre de Référence Neuropathies Périphériques Rares, CHU Limoges; 🇫🇷 Limoges, France

Département de Neurologie Pôle Neurosciences Centre de Référence des Neuropathies Amyloïdes Familiales et autres Neuropathies Périphériques Rares Centre Hospitalier Universitaire de Bicêtre; 🇫🇷 Paris, France

Referral centre for neuromuscular diseases and ALS, hôpital La Timone; 🇫🇷 Marseille, France

UMC Utrecht Cancer Center; 🇳🇱 Utrecht, Netherlands

National hospital for neurology and neurosurgery, Queen London; 🇬🇧 London, United Kingdom