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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
Intramuscular (IM) injection comprised of self-assembling nanoparticles of gluten peptides and a rapamycin component
Intramuscular (IM) injection comprised of saline solution
Parexel EPCU LA
Los Angeles, California, United States
RECRUITINGPeak Gastroenterology Associates
Colorado Springs, Colorado, United States
RECRUITINGJacksonville Center for Clinical Research
Jacksonville, Florida, United States
RECRUITINGGCP Research
St. Petersburg, Florida, United States
RECRUITINGParexel EPCU Baltimore
Baltimore, Maryland, United States
RECRUITINGClinical Research Institute of Michigan
Clinton Township, Michigan, United States
RECRUITINGWest Michigan Clinical Research Center
Wyoming, Michigan, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITINGNYU Langone - Gastroenterology Associates
New York, New York, United States
RECRUITINGNorth Carolina Clinical Research
Raleigh, North Carolina, United States
RECRUITING...and 6 more locations
Treatment Emergent Adverse Events, Serious Adverse Events and Adverse Events of Special Interest (AESIs)
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
Time frame: 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
Changes from baseline and clinically significant abnormalities in standard clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Time frame: 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
Measurement of in standard clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Time frame: 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
Measurement of standard hematology clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Time frame: 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
Measurement of standard urinalysis clinical laboratory safety parameters according to NCI CTCAE Version 5.0
Time frame: 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
Changes from baseline and clinically significant abnormalities in 12-lead ECG parameters recorded according to NCI CTCAE Version 5.0
Time frame: 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
Changes from baseline and clinically significant abnormalities in vital signs according to NCI CTCAE Version 5.0
Time frame: 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
Measurement of anti tTG immunoglobulin at screening and post treatment
Time frame: 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
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.
Time frame: Participants will be assessed for up to 21 days and 57 days post first dose for SAD and MAD parts of the study respectively.
PART A SAD:Maximum concentration in plasma (Cmax) rapamycin component
Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
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Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
Blood concentration of the rapamycin component of VTP1000 at specified timepoints measured using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and standard pharmacokinetic parameters
Time frame: 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
The Maximum concentration in plasma (Cmax) results will be reviewed from Part A (SAD) and the Part B (MAD) schedule may be updated accordingly to include additional sampling timepoints and inclusion of the derivation of pharmacokinetic parameters, as applicable.
Time frame: 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
The Cmax(Tmax) results will be reviewed from Part A (SAD) and the Part B (MAD) schedule may be updated accordingly to include additional sampling timepoints and inclusion of the derivation of pharmacokinetic parameters, as applicable.
Time frame: 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
The AUC from time 0 to last quantifiable concentration (AUC0-t) results will be reviewed from Part A (SAD) and the Part B (MAD) schedule may be updated accordingly to include additional sampling timepoints and inclusion of the derivation of pharmacokinetic parameters, as applicable.
Time frame: 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
The pharmacokinetic results will be reviewed from Part A (SAD) and the Part B (MAD) schedule may be updated accordingly to include additional sampling timepoints and inclusion of the derivation of pharmacokinetic parameters, as applicable.
Time frame: 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
The Half-life results will be reviewed from Part A (SAD) and the Part B (MAD) schedule may be updated accordingly to include additional sampling timepoints and inclusion of the derivation of pharmacokinetic parameters, as applicable.
Time frame: 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
The clearance of rapamycin component results will be reviewed from Part A (SAD) and the Part B (MAD) schedule may be updated accordingly to include additional sampling timepoints and inclusion of the derivation of pharmacokinetic parameters, as applicable.
Time frame: Part B (MAD): Days 1, 15 and 29 pre-dose and 4 hours (±10 minutes) post-dose; Day 43 pre-challenge and Day 50