Anti-MAG NeuropathyPhase 1/2NCT04568174
First in Human Study to Test the Safety and Preliminary Efficacy of PPSGG in Patients With Anti-MAG Neuropathy
A Phase 1/2 study testing PPSGG in people with Anti-MAG Neuropathy, run by Polyneuron Pharmaceuticals AG at 7 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Anti-MAG Neuropathy
- What is being tested?
- PPSGG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 17 Nov 2020to 23 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
France3 sites
Service de Neurologie Centre de Référence Neuropathies Périphériques Rares, CHU Limoges
Limoges, 87 042
Referral centre for neuromuscular diseases and ALS, hôpital La Timone
Marseille, 13385
Département de Neurologie Pôle Neurosciences Centre de Référence des Neuropathies Amyloïdes Familiales et autres Neuropathies Périphériques Rares Centre Hospitalier Universitaire de Bicêtre
Paris, 94275
United Kingdom1 site
National hospital for neurology and neurosurgery, Queen London
London, WC1N 3bg
About this study
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
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.
Read the 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.
- Conditions
- Anti-MAG Neuropathy
- Being tested
- PPSGG, Placebo
- Keywords
- peripheral neuropathy
- Medical subject headings
- Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PPSGGDrug
Also called PN-1007
an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies
PlaceboDrug
A standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection
| Study group | Role | What they receive |
|---|---|---|
| PPSGG | Active comparator | 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. Receives: Drug: PPSGG |
| Placebo | Placebo comparator | standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs) and Serious Adverse Events (SAEs)
All AEs will be recorded, whether considered minor or serious, drug-related or not
Measured: 1 month
anti-drug-antibodies ADA
Potential ADAs (immunogenicity) resulting from exposure of patients to PPSGG (PN-1007) will be measured by ELISA
Measured: 1 month in SAD
Secondary outcomes (6)
Tmax
Time of peak concentration of PPSGG (PN-1007)
Measured: Day 1 to Day 42
Cmax
Maximum Plasma Concentration of PPSGG (PN-1007)
Measured: Day 1 to Day 42
AUCinf
Area under the plasma concentration versus time curve from zero to infinity of PPSGG (PN-1007)
Measured: Day 1 to Day 42
t1/2
Terminal half life of PPSGG (PN-1007)
Measured: Day 1 to Day 42
Pharmacodynamic
Change in anti-MAG Buhlmann titer from baseline measured by ELISA
Measured: 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
Measured: up to Day 150 in MAD
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2020
- Study start17 Nov 2020
- Primary completion23 Sep 2021
- Study completion23 Sep 2021
Why it stopped: Data don't support further development
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anti-MAG NeuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single Group in SAD and parallel in MAD
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Polyneuron Pharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hedvika Lazar, Study chair, Polyneuron Pharmaceuticals AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04568174
- Sponsor's protocol ID
- PN-1007-001
- Status last verified
- Oct 2021
- First submitted
- 8 Sep 2020
- Last updated
- 15 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04568174
- Acronym / sponsor ID
- PN-1007-001
- Conditions
- Anti-MAG Neuropathy
- Keywords
- peripheral neuropathy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data don't support further development
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Polyneuron Pharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- 17 Nov 2020 (actual)
- Primary completion
- 23 Sep 2021 (actual)
- Study completion
- 23 Sep 2021 (actual)
- First posted
- 29 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Single Group in SAD and parallel in MAD
| Arm | Type | Receives |
|---|---|---|
| PPSGG | Active comparator | Drug: PPSGGsterile 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. |
| Placebo | Placebo comparator | Drug: Placebostandard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PPSGGAlso: PN-1007an antibody scavenger of pathogenic anti-MAG immunoglobulin M (IgM) autoantibodies | Drug | PPSGG |
| PlaceboA standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection | Drug | Placebo |
Primary outcome
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 1 month
All AEs will be recorded, whether considered minor or serious, drug-related or not
anti-drug-antibodies ADA
Time frame: 1 month in SAD
Potential ADAs (immunogenicity) resulting from exposure of patients to PPSGG (PN-1007) will be measured by ELISA
6 secondary outcomes
Tmax
Time frame: Day 1 to Day 42
Cmax
Time frame: Day 1 to Day 42
AUCinf
Time frame: Day 1 to Day 42
t1/2
Time frame: Day 1 to Day 42
Pharmacodynamic
Time frame: up to Day 28
Change From Baseline in ONLS
Time frame: up to Day 150 in MAD
Results and safety
The study was stopped early (reason given: Data don't support further development). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Individual participant dataSharing planned: No
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RecruitingPhase 2
Zanubritnib and Anti-MAG Neuropathy
Anti-MAG IgM-associated Demyelinating Polyneuropathy
Enrolling by invitationObservational study
This Study Aims to Investigate the Efficacy of Photobiomodulation in the Treatment of Anti-MAG-induced Peripheral Neuropathy (LASER-MAG)
Anti MAG Neuropathy
RecruitingObservational study
Studying Nerve Function and Structure in Charcot-Marie-Tooth Disease, Anti-MAG Neuropathy and CIDP
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Immunoglobulin M (IgM)-Anti-myelin-associated-glycoprotein(MAG) Peripheral Neuropathy Study
Immunoglobin M Anti-myelin-associated-glycoprotein Peripheral Neuropathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hedvika Lazar study chair
Polyneuron Pharmaceuticals AG
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PPSGG in people with Anti-MAG Neuropathy, run by Polyneuron Pharmaceuticals AG at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France, Netherlands, Spain, Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Data don't support further development). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2021.