VTP-1000 in Adults With Celiac Disease
ConditionCeliac Disease
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-70
SponsorBarinthus Biotherapeutics
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Refractory celiac disease
Selective IgA deficiency
Positive for HLA-DQ8
Known wheat allergy or that is Type I hypersensitivity
Trial design
Design model
Sequential
Treatments tested in this trial
VTP-1000
Biological/VaccineIntramuscular (IM) injection comprised of self-assembling nanoparticles of gluten peptides and a rapamycin component
Matched Placebo
Other interventionIntramuscular (IM) injection comprised of saline solution
Treatment groups
45 Participants
are divided into 8 treatment groups8
Treatment groupsSee each treatment group below.
Group A: Matched Placebo (SAD)Placebo comparator 1 intervention
Group B: VTP-1000 Dose 1 (SAD)Experimental treatment 1 intervention
Group C: VTP-1000 Dose 2 (SAD)Experimental treatment 1 intervention
Group D: VTP-1000 Dose 3 (SAD)Experimental treatment 1 intervention
Group E: Matched Placebo (MAD)Placebo comparator 1 intervention
Group F: VTP-1000 Dose 1 (MAD)Experimental treatment 1 intervention
Group G: VTP-1000 Dose 2 (MAD)Experimental treatment 1 intervention
Group H: VTP-1000 Dose 3 (MAD)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.2
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.3
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.4
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.Secondary outcomes
1
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).2
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).3
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).4
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).Other outcomes
1
Gluten Antigen-specific T Cell Responses - Enzyme linked immunospot (ELISpot)
Peripheral Blood Mononucleocytes (PBMCs) will be isolated at the trial site or at a Central Laboratory. Following PBMC isolation, analysis of the magnitude of gluten antigen-specific T cell responses (Treg and Teff) in peripheral blood will be performed by the sponsor using enzyme linked immunospot (ELISpot)
Time frame
Part A (SAD): Day 1 pre-dose, Days 8 and 15 Part B (MAD): Day 1 pre-dose, Days 8, 22 and 36, Day 43 pre-challenge, Days 50 and 572
T cell receptor (TCR) sequencing
Whole Blood sampling with sequencing The whole blood will be isolated, frozen and stored at -80°C until shipped for analysis. Full details on blood sample collection, processing and handling requirements will be provided in the Laboratory Manual
Time frame
Part A (SAD): Day 1 pre-dose, Day 15 Part B (MAD): Day 1 pre-dose, Day 43 pre-challenge and Day 573
Serum Cytokine Concentrations
2 mL whole blood samples will be drawn for evaluation of Interleukin 2 (IL-2) in serum.Samples will be stored at -80°C until shipped to a Central Laboratory for analysis. Full details on blood sample collection, processing and handling requirements will be provided in the Laboratory Manual. Analysis of IL-2 concentration (and optionally additional cytokines) will be performed at the Central Laboratory using a multiplex cytokine (Meso Scale Discovery S-plex) method as specified in the respective Analytical Protocol.
Time frame
SAD Day 1 pre-dose, 4 hours and 24 hours postdose MAD: Days 1, 15 and 29 pre-dose and 4 hours post-dose4
Cytokine Whole Blood Stimulation
Five 4 mL samples will be drawn and transferred to Greiner Item Number 454088 Vacuette® tubes containing stimulation cocktails for evaluation of cytokines in whole blood stimulated with GLU peptide antigens.Samples will be incubated for 24 hours before processing to sera and stored at -80°C until shipped for analysis. Full details on blood sample collection, processing and handling requirements will be provided in the Laboratory Manual. Analysis of sera will be performed at a Central Laboratory using a single or multiplex cytokine method as specified in the respective Analytical Protocol.
Time frame
Part A (SAD): Day 1 pre-dose, Days 8 and 15 Part B (MAD): Day 1 pre-dose, Days 8, 22 and 36, Day 43 pre-challenge and Days 50 and 57Sponsors and contacts
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Source ClinicalTrials.gov