Clinical trial NCT04568174: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Anti-MAG Neuropathy
Keywords: peripheral neuropathy
Lead sponsor: Polyneuron Pharmaceuticals AG
Sponsor class: INDUSTRY
First posted: 2020-09-29
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single Group in SAD and parallel in MAD
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 1 month
measure: anti-drug-antibodies ADA
timeFrame: 1 month in SAD
Secondary outcomes:
measure: Tmax
timeFrame: Day 1 to Day 42
measure: Cmax
timeFrame: Day 1 to Day 42
measure: AUCinf
timeFrame: Day 1 to Day 42
measure: t1/2
timeFrame: Day 1 to Day 42
measure: Pharmacodynamic
timeFrame: up to Day 28
measure: Change From Baseline in ONLS
timeFrame: up to Day 150 in MAD
Other outcomes:
Locations:
city: Limoges
country: France
facility: Service de Neurologie Centre de Référence Neuropathies Périphériques Rares, CHU Limoges
city: Marseille
country: France
facility: Referral centre for neuromuscular diseases and ALS, hôpital La Timone
city: Paris
country: France
facility: Département de Neurologie Pôle Neurosciences Centre de Référence des Neuropathies Amyloïdes Familiales et autres Neuropathies Périphériques Rares Centre Hospitalier Universitaire de Bicêtre
city: Utrecht
country: Netherlands
facility: UMC Utrecht Cancer Center
city: Barcelona
country: Spain
facility: Barcelona
city: Lausanne
country: Switzerland
facility: Lausanne
city: London
country: United Kingdom
facility: National hospital for neurology and neurosurgery, Queen London
Study officials:
affiliation: Polyneuron Pharmaceuticals AG
name: Hedvika Lazar
role: STUDY_CHAIR
References: