First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of PPSGG (PN-1007) in Anti-MAG Neuropathy Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 7
- 主要终点
- anti-drug-antibodies ADA
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The SAD phase is open label and MAD is randomized, dose escalation, double blind (patient and investigator blinded), placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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,
- •Clear clinical signs of disability
- •Adequate hepatic and renal function
排除标准
- •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
研究组 & 干预措施
PPSGG
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.
干预措施: PPSGG (Drug)
Placebo
standard PBS solution, pH 7.4, composed of disodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, sodium chloride, and water for injection
干预措施: Placebo (Drug)
结局指标
主要结局
anti-drug-antibodies ADA
时间窗: 1 month in SAD
Potential ADAs (immunogenicity) resulting from exposure of patients to PPSGG (PN-1007) will be measured by ELISA
Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 1 month
All AEs will be recorded, whether considered minor or serious, drug-related or not
次要结局
- Tmax(Day 1 to Day 42)
- Cmax(Day 1 to Day 42)
- AUCinf(Day 1 to Day 42)
- t1/2(Day 1 to Day 42)
- Pharmacodynamic(up to Day 28)
- Change From Baseline in ONLS(up to Day 150 in MAD)