First in Human Study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of PPSGG (PN-1007) in anti-MAG neuropathy patients.
- Conditions
- anti-MAG neuropathyauto-immune10012303
- Registration Number
- NL-OMON49059
- Lead Sponsor
- Polyneuron Pharmaceuticals AG
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 9
- Written informed consent.
- Age between 18 and 80 years, male and female.
- Patient with a confirmed diagnosis of monoclonal IgM associated with
monoclonal gammopathy of undetermined significance (MGUS) with anti-MAG
activity (titer of > 10*000 Bühlmann Titer units [BTU]) and demyelinating
neuropathy defined by electrophysiological criteria according to European
Federation of Neurological Societies/Peripheral Nervous System paraproteinemic
demyelinating neuropathy (EFNS/PNS PDN) guideline, 2010.
- Clear clinical signs of disability: with at least ONLS * 2 in lower
extremities.
- Inflammatory Neuropathy Cause and Treatment sensory sum score (ISS) * 2.
- Patients must have adequate hepatic function as evidenced by total bilirubin
< 26 µmol/l (1.5 mg/dL), and alkaline phosphatase and aspartate
transaminase/alanine aminotransferase < 2X the upper limit of normal (ULN).
- Absence of cause of neuropathy independent from anti- MAG activity: e.g.
diabetes, hypothyroidism, past or current dependence on alcohol, past or
current treatment with neurotoxic drugs.
- Patients must have adequate renal function as evidenced by serum creatinine
<2 mg/dL or calculated creatinine clearance of *60 mL/min within 28 days before
the first investigational medicinal product (IMP) administration using the
Modification of Diet in Renal Disease (MDRD) formula.
- Capability to meet the requirements of the study.
- Patients with total serum IgM levels >30 g.
- Hematological malignancy (e.g. known multiple myeloma or confirmed
Waldenström's macroglobulinemia based on bone marrow analysis).
- Patients with any history of malignancy of any organ system (other than
localized basal cell carcinoma of the skin), treated or untreated, within the
past 5 years, regardless of whether there is evidence of local recurrence or
metastases.
- Previous immunosuppressive treatment with intravenous immunoglobulin (IVIG)
or apheresis/plasmapheresis in the preceeding 3 months, and/or cyclophosphamide
and biologicals (e.g. rituximab): in the preceeding 6 months prior to enrolment.
- Other neurological, neuromuscular, rheumatologic or orthopedic conditions
with significant impact on the capability of walking preventing evaluation of
neurological scores.
- Anti-MAG neuropathy patients with persistent clinically significant
laboratory abnormalities not related to the anti-MAG neuropathy, such as
significant renal dysfunction, hepatic dysfunction, cardiac disease or other
significant neurological disorder.
- Anti-MAG neuropathy patients with a modified Rankin Scale (mRS) score > 4.
- Participation in another interventional clinical trial.
- Any other significant finding that would increase, according to the
Investigator, the risk of having an adverse outcome from participating in the
study.
- Any other medical condition, including mental illness or substance abuse
deemed by the investigator(s) to likely interfere with the patient's ability to
sign informed consent, cooperate and participate in the study, or interfere
with the interpretation of the results.
- Patients who have undergone major surgery * 2 weeks prior to starting study
drug or who have not recovered from the side-effects of surgery.
- A history of clinically significant ECG abnormalities, or any of the
following ECG abnormalities at screening:
PR > 200 msec.; QRS complex > 120 msec.; QTcF > 450 msec (males); QTcF > 460
msec (females); History of familial long QT syndrome or known family history of
Torsades de Pointes; Use of agents known to prolong the QT interval unless they
can be permanently discontinued for the duration of the study.
- Sexually active males must use a condom during intercourse after the start of
the IMP administration and for at least one week after stopping study
medication and should not father a child in this period after completion of the
study medication (SAD and MAD phases). A condom is required to be used also by
vasectomized men in order to prevent delivery of the drug via seminal fluid. In
addition, male participants should not donate sperm for the time period
specified above.
- Use of other investigational drugs at the time of enrolment, or within 5
half-lives of enrolment, or within 30 days, whichever is longer; or longer if
required by local regulations.
- Women of child-bearing potential, defined as all women physiologically
capable of becoming pregnant, unless they are using highly effective methods of
contraception during dosing and for 1 week after discontinuation of the
investigational drug.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method