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

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

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.

Study Overview

• Status: Terminated
• Conditions: Anti-MAG Neuropathy
• Intervention / Treatment: Drug: PPSGG; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Limoges, France, 87 042
    • Service de Neurologie Centre de Référence Neuropathies Périphériques Rares, CHU Limoges
  • Marseille, France, 13385
    • Referral centre for neuromuscular diseases and ALS, hôpital La Timone
  • Paris, France, 94275
    • Département de Neurologie Pôle Neurosciences Centre de Référence des Neuropathies Amyloïdes Familiales et autres Neuropathies Périphériques Rares Centre Hospitalier Universitaire de Bicêtre
• Netherlands
  • Utrecht, Netherlands
    • UMC Utrecht Cancer Center
• Spain
  • Barcelona, Spain
    • Barcelona
• Switzerland
  • Lausanne, Switzerland
    • Lausanne
• United Kingdom
  • London, United Kingdom, WC1N 3bg
    • National hospital for neurology and neurosurgery, Queen London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: PPSGG; an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies; Other Names: PN-1007
Placebo Comparator: Placebo; standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection	Drug: Placebo; A standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Polyneuron Pharmaceuticals AG
• Investigators: Study Chair: Hedvika Lazar, Polyneuron Pharmaceuticals AG

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): September 23, 2021
• Study Completion (Actual): September 23, 2021

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: peripheral neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: PN-1007-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No