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

Sponsor

Polyneuron Pharmaceuticals AG (Industry)

Overall Status

Terminated

CT.gov ID

NCT04568174

Collaborator

(none)

Enrollment

Locations

Arms

10.2

Actual Duration (Months)

0.1

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Anti-MAG Neuropathy	Drug: PPSGG Drug: Placebo	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single Group in SAD and parallel in MADSingle Group in SAD and parallel in MAD

Masking:

Triple (Participant, 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

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 17, 2020

Actual Primary Completion Date :

Sep 23, 2021

Actual Study Completion Date :

Sep 23, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Polyneuron Pharmaceuticals AG

Investigators

Study Chair: Hedvika Lazar, Polyneuron Pharmaceuticals AG

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Polyneuron Pharmaceuticals AG

ClinicalTrials.gov Identifier:

NCT04568174

Other Study ID Numbers:

PN-1007-001

First Posted:

Sep 29, 2020

Last Update Posted:

Oct 15, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Polyneuron Pharmaceuticals AG

peripheral neuropathy

Additional relevant MeSH terms:

Peripheral Nervous System Diseases

Study Results

No Results Posted as of Oct 15, 2021