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

Primary Purpose

Anti-MAG Neuropathy

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PPSGG
Placebo
Sponsored by
Polyneuron Pharmaceuticals AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anti-MAG Neuropathy focused on measuring peripheral neuropathy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Service de Neurologie Centre de Référence Neuropathies Périphériques Rares, CHU Limoges
  • Referral centre for neuromuscular diseases and ALS, hôpital La Timone
  • Département de Neurologie Pôle Neurosciences Centre de Référence des Neuropathies Amyloïdes Familiales et autres Neuropathies Périphériques Rares Centre Hospitalier Universitaire de Bicêtre
  • UMC Utrecht Cancer Center
  • Barcelona
  • Lausanne
  • National hospital for neurology and neurosurgery, Queen London

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

PPSGG

Placebo

Arm Description

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.

standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 8, 2020
Last Updated
October 7, 2021
Sponsor
Polyneuron Pharmaceuticals AG
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1. Study Identification

Unique Protocol Identification Number
NCT04568174
Brief Title
First in Human Study to Test the Safety and Preliminary Efficacy of PPSGG in Patients With Anti-MAG Neuropathy
Official Title
First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of PPSGG (PN-1007) in Anti-MAG Neuropathy Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Data don't support further development
Study Start Date
November 17, 2020 (Actual)
Primary Completion Date
September 23, 2021 (Actual)
Study Completion Date
September 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Polyneuron Pharmaceuticals AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anti-MAG Neuropathy
Keywords
peripheral neuropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Single Group in SAD and parallel in MAD
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
The SAD phase is open label and MAD is randomized, dose escalation, double blind (patient and investigator blinded), placebo-controlled
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PPSGG
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection
Intervention Type
Drug
Intervention Name(s)
PPSGG
Other Intervention Name(s)
PN-1007
Intervention Description
an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection
Primary Outcome Measure Information:
Title
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
All AEs will be recorded, whether considered minor or serious, drug-related or not
Time Frame
1 month
Title
anti-drug-antibodies ADA
Description
Potential ADAs (immunogenicity) resulting from exposure of patients to PPSGG (PN-1007) will be measured by ELISA
Time Frame
1 month in SAD
Secondary Outcome Measure Information:
Title
Tmax
Description
Time of peak concentration of PPSGG (PN-1007)
Time Frame
Day 1 to Day 42
Title
Cmax
Description
Maximum Plasma Concentration of PPSGG (PN-1007)
Time Frame
Day 1 to Day 42
Title
AUCinf
Description
Area under the plasma concentration versus time curve from zero to infinity of PPSGG (PN-1007)
Time Frame
Day 1 to Day 42
Title
t1/2
Description
Terminal half life of PPSGG (PN-1007)
Time Frame
Day 1 to Day 42
Title
Pharmacodynamic
Description
Change in anti-MAG Buhlmann titer from baseline measured by ELISA
Time Frame
up to Day 28
Title
Change From Baseline in ONLS
Description
Overall Neuropathy Limitations Scale measures limitations in the everyday activities of the upper and lower limbs
Time Frame
up to Day 150 in MAD

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hedvika Lazar
Organizational Affiliation
Polyneuron Pharmaceuticals AG
Official's Role
Study Chair
Facility Information:
Facility Name
Service de Neurologie Centre de Référence Neuropathies Périphériques Rares, CHU Limoges
City
Limoges
ZIP/Postal Code
87 042
Country
France
Facility Name
Referral centre for neuromuscular diseases and ALS, hôpital La Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Département de Neurologie Pôle Neurosciences Centre de Référence des Neuropathies Amyloïdes Familiales et autres Neuropathies Périphériques Rares Centre Hospitalier Universitaire de Bicêtre
City
Paris
ZIP/Postal Code
94275
Country
France
Facility Name
UMC Utrecht Cancer Center
City
Utrecht
Country
Netherlands
Facility Name
Barcelona
City
Barcelona
Country
Spain
Facility Name
Lausanne
City
Lausanne
Country
Switzerland
Facility Name
National hospital for neurology and neurosurgery, Queen London
City
London
ZIP/Postal Code
WC1N 3bg
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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