A Phase 1, First in Human, Randomized, Placebo-controlled Trial With a Controlled Gluten Challenge to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VTP-1000 in Adults With Celiac Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 30
- 主要终点
- Changes from baseline and clinically significant abnormalities in vital signs
研究概览
简要总结
GLU001 is a first-in-human clinical trial to assess the safety and tolerability of VTP-1000 for adults with celiac disease. This trial will assess VTP-1000 at various dose levels compared to placebo in a single ascending dose (SAD) and multiple ascending dose (MAD) format. Participants will be followed for a short period of time to assess the impact of VTP-1000 on their immune system (Adverse events, reactions in the blood, and physical exam differences). Participants enrolled in the MAD portion of the trial will undergo a gluten challenge to assess the impact exposure to gluten has on participants after administration of VTP-1000.
详细描述
VTP-1000 is a gluten-derived (GLU) peptide immunotherapy that is designed to induce antigen-specific immune tolerance against gluten in patients with celiac disease. The technology underlying VTP-1000 consists of the sponsor's proprietary self-assembling nanoparticles based on amphiphilic peptides tolerance immunotherapy (SNAP-TI) platform which has been configured to package 12 GLU peptide antigens and rapamycin into nanoparticles of ~20 nm diameter.
The goal of treatment with VTP-1000 is to induce tolerance to gluten in patients with coeliac disease by activating antigen-specific regulatory T (Treg) cells that promote tolerance and reducing pre-existing, pathogenic antigen-specific effector T (Teff) cells that underly disease pathogenesis. In turn, this may allow for better management of the condition.
GLU001 is a multi-center phase I first in human study to assess the safety and tolerability of VTP-1000 in adults with celiac disease. The trial also aims to demonstrate proof-of-principle of induction of immune tolerance and early proof-of-concept for VTP-1000 as a potential treatment for coeliac disease based on assessment of pharmacodynamics and preliminary efficacy determined by means of a controlled gluten challenge.
GLU001 will be conducted as a randomized double-blind placebo-controlled study in two parts - Part A and Part B. Part A will be a single ascending dose (SAD) followed by Part B a multiple ascending dose (MAD) which incorporates a gluten challenge.
Part A (Single Ascending Dose)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of celiac disease as confirmed by positive serology and intestinal histology
- •Presence of Human Leukocyte Antigen (HLA)-DQ2.5 genotype
- •Participants who are on a well controlled gluten restricted diet
- •Anti-tissue transglutaminase (tTG) IgA antibodies less than 2 times the upper limit of normal and anti-deamidated gliadin peptide IgG (anti-DGP)-IgA/IgA antibodies less than 3 times the upper limit of normal
- •Non-pregnant or breast feeding females
- •No other clinical significant findings at screening
排除标准
- •Refractory celiac disease
- •Selective IgA deficiency
- •Positive for HLA-DQ8
- •Known wheat allergy or that is Type I hypersensitivity
- •Active inflammatory bowel disease or other condition with symptoms that will be similar to celiac disease
研究组 & 干预措施
VTP-1000 Dose 3 (SAD)
3 dose levels in SAD and MAD parts of trial
干预措施: VTP-1000 (Biological)
VTP-1000 Dose 1 (MAD)
3 dose levels in SAD and MAD parts of trial
干预措施: VTP-1000 (Biological)
VTP-1000 Dose 2 (MAD)
3 dose levels in SAD and MAD parts of trial
干预措施: VTP-1000 (Biological)
VTP-1000 Dose 3 (MAD)
3 dose levels in SAD and MAD parts of trial
干预措施: VTP-1000 (Biological)
Matched Placebo (MAD)
2 placebo comparators; 1 for each part of the study
干预措施: Matched Placebo (Other)
VTP-1000 Dose 2 (SAD)
3 dose levels in SAD and MAD parts of trial
干预措施: VTP-1000 (Biological)
Matched Placebo (SAD)
2 placebo comparators; 1 for each part of the study
干预措施: Matched Placebo (Other)
VTP-1000 Dose 1 (SAD)
3 dose levels in SAD and MAD parts of trial
干预措施: VTP-1000 (Biological)
结局指标
主要结局
Changes from baseline and clinically significant abnormalities in vital signs
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Changes from baseline and clinically significant abnormalities in vital signs according to NCI CTCAE Version 5.0
Number of participants with changes from baseline in anti-tissue transglutaminase (anti-tTG) immunoglobulin A (IgA) antibodies
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Measurement of anti tTG immunoglobulin at screening and post treatment
Changes in physical examination findings
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Full physical examination required at screening; symptom-directed physical examination at all other clinic visits. Each physical examination must include a review of the administration sites.
Treatment Emergent Adverse Events, Serious Adverse Events and Adverse Events of Special Interest (AESIs)
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Incidence and severity of treatment-emergent adverse events (TEAEs) , Serious Adverse Events (SAEs) , Adverse Events of Special Interest (AESIs) and adverse events leading to trial intervention discontinuation or trial withdrawal according to NCI CTCAE Version 5.0
Changes from baseline and clinically significant abnormalities in standard Clinical Chemistry laboratory safety parameters
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Changes from baseline and clinically significant abnormalities in standard clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Changes from baseline and clinically significant abnormalities in standard Coagulation laboratory safety parameters
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Measurement of in standard clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Changes from baseline and clinically significant abnormalities in standard hematology laboratory safety parameters
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Measurement of standard hematology clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Changes from baseline and clinically significant abnormalities in standard urinalysis laboratory safety parameters
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Measurement of standard urinalysis clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Changes from baseline and clinically significant abnormalities 12-lead electrocardiogram (ECG) parameters
时间窗: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
Changes from baseline and clinically significant abnormalities in 12-lead ECG parameters recorded according to NCI CTCAE Version 5.0
次要结局
- PART A SAD:Maximum concentration in plasma (Cmax) rapamycin component(SAD Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- Volume of distribution of rapamycin component(Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- Part B MAD:Time corresponding to Cmax (Tmax) of rapamycin component(Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50)
- PART A SAD: Time corresponding to Cmax (Tmax) of rapamycin component(Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- AUC from time 0 to last quantifiable concentration (AUC0-t) of rapamycin component(Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- AUC extrapolated to infinity (AUC0-∞)of rapamycin component(Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- Half-life of rapamycin component(Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- Clearance of rapamycin component(Day 1 pre-dose; 0.083 hours* (±2 minutes), 0.25 hours* (±5 minutes), 0.5 hours (±5 minutes), 1 hour (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (±10 minutes), 24 hours (±30 minutes), 48 hours (±2 hours), 120 hours (±3 hours).)
- Part B MAD:Maximum concentration in plasma (Cmax) rapamycin component(Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50)
- Part B MAD:AUC from time 0 to last quantifiable concentration (AUC0-t) of rapamycin component(Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50)
- Part B MAD: Half-life of rapamycin component(Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50)
- Part B MAD:AUC extrapolated to infinity (AUC0-∞)of rapamycin component(Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50)
- Part B MAD: Clearance of rapamycin component(Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50)