VTP-1000 in Adults With Celiac Disease
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: VTP-1000, Matched Placebo.
- Кому может быть актуально
- Состояния в реестре: Celiac Disease. Базовые параметры: 18 лет — 70 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- США
- Следующий шаг
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Официальное название
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
Обзор
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.
Подробное описание
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)
A stepwise single dose escalation of 3 dose levels of VTP-1000 is planned. A total of 6 participants will be treated at each dose level (4 will receive VTP-1000 and 2 will receive matched placebo). A sentinel dosing approach will be followed, with the first 2 participants randomized to receive VTP1000 or placebo in a 1:1 ratio. Subsequent participants will be randomized in a 3:1 ratio at least 7 days after the second sentinel participant has received trial intervention. Participants will be screened for eligibility up to 28 days prior treatment. Participants will be followed for 21 days after dosing including a 3-day domicile period following administration of VTP-1000.
Part B (Multiple Ascending Dose)
A stepwise multiple dose escalation of up to 3 dose levels of VTP-1000 is planned. A total of 8 participants will be treated at each dose level (6 will receive VTP-1000 and 2 will receive matched placebo). A sentinel dosing approach will be followed in the first dose level only, with the first 2 participants randomized to receive VTP1000 or placebo in a 1:1 ratio. Subsequent participants at the first dose level will be randomized in a 5:1 ratio at least 7 days after the second sentinel participant has received trial intervention. Participants in the second and third dose levels will be randomized in a 6:2 ratio, and no sentinel dosing sequence will be applied.
Participants will be screened for eligibility up to 28 days prior to the start of treatment. Eligible participants will receive 3 doses of trial intervention every 2 weeks at a given dose level with and followed for 57 days. After completion of the third dose of trial intervention, participants will undergo a gluten challenge.
Вмешательства
- Биопрепарат VTP-1000
Intramuscular (IM) injection comprised of self-assembling nanoparticles of gluten peptides and a rapamycin component - Другое Matched Placebo
Intramuscular (IM) injection comprised of saline solution
Первичные конечные точки
- Treatment Emergent Adverse Events, Serious Adverse Events and Adverse Events of Special Interest (AESIs) [Срок оценки: 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 Chemistry laboratory safety parameters [Срок оценки: 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 Coagulation laboratory safety parameters [Срок оценки: 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 hematology laboratory safety parameters [Срок оценки: 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 urinalysis laboratory safety parameters [Срок оценки: 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 12-lead electrocardiogram (ECG) parameters [Срок оценки: 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 [Срок оценки: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.]
- Number of participants with changes from baseline in anti-tissue transglutaminase (anti-tTG) immunoglobulin A (IgA) antibodies [Срок оценки: 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 in physical examination findings [Срок оценки: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.]
Вторичные конечные точки (12)
- PART A SAD:Maximum concentration in plasma (Cmax) rapamycin component [Срок оценки: 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).]
- PART A SAD: Time corresponding to Cmax (Tmax) of rapamycin component [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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:Time corresponding to Cmax (Tmax) of rapamycin component [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50]
Критерии участия
Критерии включения
- 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
Критерии исключения
- 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
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Рандомизированное
- Модель
- Последовательный дизайн
- Маскирование
- Четверное слепое
- Основная цель
- Лечение
Центры проведения
США · 16 центров
- Parexel EPCU LA — Los Angeles
- Peak Gastroenterology Associates — Colorado Springs
- Jacksonville Center for Clinical Research — Jacksonville
- GCP Research — St. Petersburg
- Parexel EPCU Baltimore — Baltimore
- Clinical Research Institute of Michigan — Clinton Township
- West Michigan Clinical Research Center — Wyoming
- Mayo Clinic — Rochester
- … и ещё 8 центров
Идентификаторы
NCT: NCT06310291 · GLU001