Clinical Trials Register

Summary
EudraCT Number:	2020-000067-23
Sponsor's Protocol Code Number:	PN-1007-001
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-03-13
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2020-000067-23

A.3

Full title of the trial

First in Human Study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of PPSGG in anti-MAG neuropathy patients

Étude de première administration chez l’homme visant à évaluer la sécurité d’emploi, la tolérance, la pharmacocinétique, la pharmacodynamique et l’efficacité préliminaire du PPSGG (PN-1007) chez des patients atteints de neuropathie anti-MAG.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

First in human study to test the safety and preliminary efficacy of PPSGG, an antibody catcher in patients with anti-MAG neuropathy

A.4.1

Sponsor's protocol code number

PN-1007-001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Polyneuron Pharmaceuticals AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Polyneuron Pharmaceuticals AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Polyneuron Pharmaceuticals
B.5.2	Functional name of contact point	Clinical Trial Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Hochbergerstrasse 60C
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4057
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41(0)61638 23 23
B.5.6	E-mail	c.trials@polyneuron.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/048/17
D.3 Description of the IMP
D.3.1	Product name	PPSGG solution for infusion
D.3.2	Product code	PPSGG
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	POLYPHENYL(DISODIUM 3-O-SULFO-BETA-D-GLUCOPYRANURONATE)-(1->3)-BETA-D-GALACTOPYRANOSIDE
D.3.9.4	EV Substance Code	SUB192728
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

anti-MAG neuropathy

E.1.1.1

Medical condition in easily understood language

Anti-MAG peripheral neuropathy is a rare disease. It occurs when the body’s own immune system develops antibodies against myelin (protein of the nerves, myelin-associated glycoprotein, MAG).

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10066137
E.1.2	Term	Anti-MAG neuropathy
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

safety and tolerability

E.2.2

Secondary objectives of the trial

pharmacokinetics of PPSGG after single and multiple intravenous administrations, pharmacodynamics, preliminary efficacy

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age between 18 and 80 years, male and female.
• Patient 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: with at least ONLS ≥ 2 in lower extremities.
• Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score ≥2.
• Adequate hepatic and renal function

E.4

Principal 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 6/12.
• Other neurological, neuromuscular, rheumatologic or orthopedic condition with significant impact on the capabilities of walk preventing evaluation of neurological scores

E.5 End points

E.5.1

Primary end point(s)

Assessment of safety based on vital signs, physical examination, ECGs, laboratory assessments, Signs of infusion-related reactions, including clinical signs and symptoms, changes in diastolic or systolic blood pressure, heart rate, oxygen saturation, and skin reactions or local reactions at the infusion site and collection of AEs assessed from baseline until the end of the study visit. Presence of Anti-drug antibodies will also be investigated

E.5.1.1

Timepoint(s) of evaluation of this end point

ECG: 1-lead during infusions, 12-lead predose, 1h, 2h, 8h post dose. On Day 2 and EOS during SAD and during MAD on infusion days (Day 1-5, 8, 14, 21, 28, 35, 42, 56), 70, 98, EOS. The same days for vital signs
Safety lab: SAD: SCR, baseline, Day 8, EOS
Safety lab: MAD: SCR, baseline, Day 8, 28, 42, 98, EOS.

E.5.2

Secondary end point(s)

PK: Non-compartmental parameters related to PPSGG, including but not limited to Tmax, Cmax, as well as trough (pre-dose) levels after multiple dose, PD: Reduction of anti-MAG antibodies and time to reduction, Time to anti-MAG IgM rebound (to pre-treatment BTU levels), Paraprotein levels (g/L), Total IgM levels (g/L), Anti-human natural killer-1 (HNK-1) IgM titers, Reduction of anti-MAG antibodies by ≥50% and time to reduction, preliminary efficacy: Change in ONLS score, Time to walk 10 meters, RODS, Ataxia score, Modified ISS, MUNIX (motor unit number index), Grip Strength

E.5.2.1

Timepoint(s) of evaluation of this end point

PK during infusion: 5, 30, 60min, 2, 6, 8 h,
PK and PD on SCR, baseline, Day 2, 4, 8 and 14 during SAD and on Day 1-5,8,14,21,28,35,42,56,70, EOS and FU during MAD
Scores: SCR, Day 14, 42, 98, EOS and 180 during MAD

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

During SAD open non controlled and during MAD double-blind placebo controlled, randomised

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

France

Netherlands

Spain

Switzerland

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Study Completion (SC) is defined as when the last patient completes their EOS visit at the end of the MAD phase, or at the end of SAD, if the patient decides not to continue with the MAD, and any repeated assessments associated with this visit have been followed-up appropriately by the investigator, or in the event of an early study termination decision, the date of that decision.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

There are currently no plans to extend use of drug to patients until long term safety data are obtained.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-04-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-01

P. End of Trial
P.	End of Trial Status	Ongoing

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