VTP-1000 for Celiac Disease

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Barinthus Biotherapeutics

Disqualifiers: Refractory celiac, IgA deficiency, others

Compensation: Varies

Number of Visits: 6

45 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How does the drug VTP-1000 for celiac disease differ from other treatments?

VTP-1000 is unique because it likely involves a glutenase similar to ALV003, which breaks down harmful gluten peptides before they can trigger an immune response in celiac patients, unlike the standard gluten-free diet that requires complete avoidance of gluten. ^{1 2 3 4 5}

What is the purpose of 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 is for adults with celiac disease who have a specific genetic marker (HLA-DQ2.5), confirmed diagnosis through tests and biopsy, are on a controlled gluten-free diet, and not pregnant or breastfeeding. They should also have low levels of certain antibodies related to celiac disease.

Inclusion Criteria

I have the HLA-DQ2.5 genotype.

Participants who are on a well controlled gluten restricted diet

I am not pregnant or breastfeeding.

Exclusion Criteria

My celiac disease does not improve with a gluten-free diet.

I have a condition where my body doesn't produce enough IgA antibodies.

I am positive for HLA-DQ8.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Single Ascending Dose (SAD)

Participants receive a single dose of VTP-1000 at escalating dose levels to assess safety and tolerability

3 weeks

Includes a 3-day domicile period following administration

Multiple Ascending Dose (MAD)

Participants receive multiple doses of VTP-1000 at escalating dose levels, followed by a gluten challenge

8 weeks

3 doses every 2 weeks, followed by gluten challenge

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VTP-1000

Trial Overview The trial is testing VTP-1000's safety and how well it's tolerated in different doses compared to a placebo. It includes single dose tests followed by multiple doses where participants will eat gluten to see if the drug reduces their immune response.

Participant Groups

Group I: VTP-1000 Dose 3 (SAD) Experimental Treatment 1 Intervention

3 dose levels in SAD and MAD parts of trial

Group II: VTP-1000 Dose 3 (MAD) Experimental Treatment 1 Intervention

3 dose levels in SAD and MAD parts of trial

Group III: VTP-1000 Dose 2 (SAD) Experimental Treatment 1 Intervention

3 dose levels in SAD and MAD parts of trial

Group IV: VTP-1000 Dose 2 (MAD) Experimental Treatment 1 Intervention

3 dose levels in SAD and MAD parts of trial

Group V: VTP-1000 Dose 1 (SAD) Experimental Treatment 1 Intervention

3 dose levels in SAD and MAD parts of trial

Group VI: VTP-1000 Dose 1 (MAD) Experimental Treatment 1 Intervention

3 dose levels in SAD and MAD parts of trial

Group VII: Matched Placebo (SAD) Placebo Group 1 Intervention

2 placebo comparators; 1 for each part of the study

Group VIII: Matched Placebo (MAD) Placebo Group 1 Intervention

2 placebo comparators; 1 for each part of the study

Who Is Running the Clinical Trial?

Barinthus Biotherapeutics

Lead Sponsor

Trials

12

Recruited

3,800+

Findings from Research

The QUANTA Lite (™) h-tTG/DGP Screen assay demonstrated 100% sensitivity and 91.12% specificity in detecting antibodies related to celiac disease in a study involving 41 celiac patients and 169 controls.

This new assay is considered superior to conventional tests and may serve as the best initial screening tool for celiac disease, potentially reducing the need for invasive duodenal biopsies in certain populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of a combination screening assay for celiac disease. Porcelli, B., Ferretti, F., Vindigni, C., et al.[2020]

In a study involving 20 patients with celiac disease, pre-treatment with ALV003, a glutenase mixture, effectively prevented immune responses to gluten, as shown by a significant reduction in T-cell responses compared to the placebo group (p=0.011).

Despite the immune response being abolished with ALV003, symptoms related to gluten ingestion were still reported in both groups, indicating that while ALV003 can block immune activation, it may not alleviate all symptoms associated with gluten consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of ALV003 pre-digestion of gluten on immune response and symptoms in celiac disease in vivo. Tye-Din, JA., Anderson, RP., Ffrench, RA., et al.[2010]

The IgA anti-tissue transglutaminase (anti-tTG) antibody assay is as reliable as the conventional IgA anti-endomysium antibody (EMA) assay for screening celiac disease in IgA-sufficient children, with a sensitivity of 89% and a negative predictive value of 98%.

Both tests showed high specificity (94% for anti-tTG and 97% for EMA), but the positive predictive value was lower for anti-tTG (67%) compared to EMA (80%), indicating that while both tests are effective, EMA may be slightly more reliable in confirming positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue transglutaminase enzyme-linked immunosorbent assay as a screening test for celiac disease in pediatric patients. Chan, AW., Butzner, JD., McKenna, R., et al.[2019]

Celiac disease affects about 1-2% of the population and requires a strict gluten-free diet (GFD) as the only effective treatment, but compliance is low at around 50%.

In children, 95% achieve normalization of duodenal mucosa within two years on a GFD, while adults may take 3-5 years for complete healing, highlighting the need for ongoing monitoring and support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive Study of the Different Tools Used to Evaluate the Adherence to a Gluten-Free Diet in Celiac Disease Patients. Rodrigo, L., Pérez-Martinez, I., Lauret-Braña, E., et al.[2019]

In a phase 2 trial involving 41 adults with celiac disease, the glutenase ALV003 significantly protected against gluten-induced mucosal injury, as evidenced by stable villus height to crypt depth ratios and intraepithelial lymphocyte counts compared to the placebo group.

While ALV003 showed efficacy in preventing mucosal damage during a gluten challenge, there were no significant differences in patient symptoms between the ALV003 and placebo groups, indicating that while the treatment may protect the intestine, it does not necessarily alleviate symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac disease. Lähdeaho, ML., Kaukinen, K., Laurila, K., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Assessment of a combination screening assay for celiac disease. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of ALV003 pre-digestion of gluten on immune response and symptoms in celiac disease in vivo. [2010]

3. United States pubmed.ncbi.nlm.nih.gov

Tissue transglutaminase enzyme-linked immunosorbent assay as a screening test for celiac disease in pediatric patients. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Descriptive Study of the Different Tools Used to Evaluate the Adherence to a Gluten-Free Diet in Celiac Disease Patients. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac disease. [2015]