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

Anti-MAG Neuropathy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04568174
• Other study ID #: PN-1007-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 17, 2020
• Est. completion date: September 23, 2021

Study information

• Verified date: October 2021
• Source: Polyneuron Pharmaceuticals AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: September 23, 2021
• Est. primary completion date: September 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Anti-MAG Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• PPSGG
an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies
• Placebo
A standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Polyneuron Pharmaceuticals AG

Countries where clinical trial is conducted

France,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events (AEs) and Serious Adverse Events (SAEs)	All AEs will be recorded, whether considered minor or serious, drug-related or not	1 month
Primary	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	Tmax	Time of peak concentration of PPSGG (PN-1007)	Day 1 to Day 42
Secondary	Cmax	Maximum Plasma Concentration of PPSGG (PN-1007)	Day 1 to Day 42
Secondary	AUCinf	Area under the plasma concentration versus time curve from zero to infinity of PPSGG (PN-1007)	Day 1 to Day 42
Secondary	t1/2	Terminal half life of PPSGG (PN-1007)	Day 1 to Day 42
Secondary	Pharmacodynamic	Change in anti-MAG Buhlmann titer from baseline measured by ELISA	up to Day 28
Secondary	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