VTP-1000 in Adults With Celiac Disease

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 65 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 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.

- Negative or weak positive anti-tissue transglutaminase (tTG) IgA antibodies and negative or weak positive anti-deamidated gliadin peptide IgG (anti-DGP)-IgA/IgA antibodies.

- Non-pregnant or breast feeding females.

- No other clinical significant findings at screening.

Exclusion Criteria:

- 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06310291
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Early Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Barinthus Biotherapeutics
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Celiac Disease

Additional Details

VTP-1000 is a gluten-derived (GLU) peptide immunotherapy that is designed to induce antigen-specific immune tolerance against gluten in patients with coeliac 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 antigenspecific effector T (Teff) cells that underly disease pathogenesis. In turn, this may allow for better management of the condition. This is the first clinical trial with VTP-1000, therefore the primary endpoint will be assessment of the safety and tolerability of single and multiple dosing and determination of a dose and schedule for further investigation. 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. Trial Design. This is a Phase I, First in Human, multicentre trial conducted in 2 parts; a randomised double-blind placebo controlled SAD part (Part A) followed by a randomised double-blind placebo-controlled MAD part (Part B) incorporating a gluten challenge component. Part A (Single Ascending Dose) A stepwise single dose escalation of 3 dose levels of VTP-1000 is planned. Participants will be screened for eligibility in the period 28 days to 2 days prior to the start of treatment. Eligible participants will be admitted to the clinic on the day before dosing (Day -1). Eligibility will be reconfirmed prior to a single dose of VTP-1000 administered by intramuscular injection on Day 1, followed by inpatient observation and assessment for a 48hour period prior to discharge from the clinic on Day 3. Participants will be followed for 21 days after dosing, with follow-up visits on Days 3, 5, 8 and 15 and an End of Trial (EOT) visit on Day 22. 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 randomised to receive VTP1000 or placebo in a 1:1 ratio. Subsequent participants will be randomised in a 3:1 ratio at least 7 days after the second sentinel participant has received trial intervention. The medical monitor will review the safety and tolerability data to confirm the safety profile is acceptable for the first 2 participants in a dose level before the next participant receives trial intervention. Subsequent participants can be dosed in parallel to the third. Part B (Multiple Ascending Dose) A stepwise multiple dose escalation of up to 3 dose levels of VTP-1000 is planned, commencing at the starting dose (and frequency) determined by the Safety Monitoring Committee (SMC) review following completion of Part A (SAD). Participants will be screened for eligibility in the period 28 days to 1 day prior to the start of treatment. Eligible participants will receive 3 doses of trial intervention every 2 weeks (on Days 1, 15 and 29) at a given dose level with follow-up on Days 8, 22 and 36. Telephone calls to the participant will also be made by the trial site staff on the day after each treatment day (Days 2, 16 and 30). Two weeks after completion of the third dose of trial intervention, participants will undergo a gluten challenge on Day 43, with a follow-up assessment on Day 50. An EOT visit will be performed on Day 57. 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, with the first 2 participants randomised to receive VTP1000 or placebo in a 1:1 ratio. Subsequent participants will be randomised in a 5:1 ratio at least 7 days after the second sentinel participant has received all 3 doses of trial intervention, following review of safety and tolerability data from the first 2 participants by the medical monitor to confirm the safety profile is acceptable.

Arms & Interventions