A Study of PVP001, PVP002, and PVP003 in Healthy Adults and PVP001 and PVP002 in Adults With Celiac Disease
Condition: Digestive System Disease
MeSH terms: Celiac Disease; Digestive System Diseases; Gastrointestinal Diseases
Intervention: PvP001 placebo; PvP001 100 mg; PvP001 300 mg; PvP001 900 mg; Maximum Feasible Dose (MFD) of PvP002; Maximum Tolerated Dose (MTD) of PvP001; MTD of PvP001 following 7 days of PPI treatment; PvP002 placebo; PvP001 600 mg; PvP003 placebo; PvP003; PvP003 150 mg
Intervention description: placebo; PvP001 100 mg; PvP001 300 mg; PvP001 900 mg; MFD of PvP002; Maximum Tolerated Dose (MTD) of PvP001; Maximum Tolerated Dose (MTD) of PvP001 following 7 days of PPI (Proton Pump Inhibitor) treatment; Placebo; PvP001 600 mg; Placebo tablet orally.; PvP003 tablet orally.; PvP003 150 mg
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Enrollment: 139.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      It is hoped that different forms of the same medicine, called PVP001, PVP002, and PVP003,
      will help people with celiac disease. Both healthy adults and adults with celiac disease will
      take part in this study.

      There are many main aims of the study.

        -  To check if participants have side effects from different forms of the study medicine.
           These forms are called PVP001 (liquid in a cup), PVP002 capsule, and PVP003 tablet.

        -  To check how well PVP003 breaks down gluten.

        -  To check how much PVP003 participants can take without getting side effects from it.

      The study is in 4 parts. At the start of each part of the study, the study doctor will check
      to determine who can take part at the first study visit. Different groups of participants
      will be in different parts of the study.

      In all parts of the study, some participants will take 1 of the 3 forms of study medicine.
      Others will take a placebo. In this study, a placebo will look like the form of study
      medicine but will not have any medicine in it. This means that a placebo can either look like
      PVP001 liquid in a cup, the PVP002 tablet, or the PVP003 tablet.

      In Part 1, different small groups of participants will take lower to higher doses of PVP001
      or PVP002 or a placebo. This is to work out the best dose of study medicine to take in other
      parts of the study. After treatment, participants will regularly visit the clinic to check
      that they have no problems with their treatment, including any side effects from their
      treatment.

      In Part 2, different small groups will take different doses of PVP001 or PVP002 or a placebo,
      either with or without a meal that has different amounts of gluten in it. This is to check if
      PVP001 or PVP002 has broken down gluten in the body. Participants will visit the clinic after
      treatment to check how much gluten has been broken down in the body.

      In Part 3, different small groups will take different doses of PVP003 or a placebo, either
      with or without a meal that has gluten in it. This is to check if PVP003 has broken down
      gluten in the body. Participants will visit the clinic after treatment to check if more
      gluten has broken down in the body.

      In Part 4, different small groups will take PVP003 or placebo 3 times a day for 5 days. After
      treatment, participants will visit the clinic to check that they have no problems with their
      treatment, including any side effects from their treatment.
    

Eligibility criteria:

        Inclusion Criteria:

        Part 1, Part 2, Part 3 and Part 4

          1. Male or female age 18- 64 years, inclusive

          2. No relevant gastrointestinal symptoms

          3. Able to abstain from alcohol for 72 hours prior to the Screening Visit; for 72 hours
             prior to and after the Cohort Treatment Day (Part 1, Part 2, and Part 3); for 72 hours
             prior to the Safety Visit (Part 2 and Part 3); and for 72 hours prior to Day 1 of the
             first Cohort Treatment Period through the Safety Visit (Part 4).

          4. A female participant must have a negative pregnancy test at Screening and on Cohort
             Treatment Day -1 (Part 1, Part 2, and Part 3) or a negative pregnancy test at
             Screening and on Day -1 of each Cohort Treatment Period (Part 4), and must agree to
             continue acceptable birth control measures (example, abstinence, a stable hormonal
             contraceptive, double-barrier method, or vasectomy in partner) from the Screening
             Visit through the 28 ± 2 days. Follow Up ADA Blood Sampling Visit

          5. A male participant must agree to use acceptable birth control measures (e.g.,
             abstinence, latex condom, or vasectomy), or must have a female partner who will
             continue birth control measures (e.g., abstinence, a stable hormonal contraceptive, or
             double-barrier method) from the Screening Visit through the 28 ± 2 days Follow Up
             Anti-Drug Antibody Blood Sampling Visit

          6. Able to read and understand English

          7. Able to provide written informed consent

             Additional Inclusion Criteria for Part 1, Part 2, Part 3, and Part 4 Healthy Adult
             Volunteers

          8. No use of over-the-counter or prescription medication, except for birth control
             medications for the duration of the study

          9. No history of gastrointestinal diseases or disorders

         10. No history of intolerance, sensitivity, or reactions to gluten or any other food or
             food ingredient

         11. Able to maintain a gluten-free diet for 24 hours prior to the Cohort Treatment Day
             (Part 1, Part 2, and Part 3), or usually ingests meals three times a day (that is,
             breakfast, lunch, and dinner) and is able to continue doing so during each Cohort
             Treatment Period (Part 4)

             Additional Inclusion Criteria for Part 1 Participants with Celiac Disease

         12. Documented history of Celiac Disease in medical records

         13. Maintaining a gluten-free diet for ≥6 months

         14. No use of over-the-counter or prescription medication, except for birth control
             medications and those allowed by the study doctor, for the duration of the study.

         15. No history of gastrointestinal diseases or disorders, other than Celiac Disease

         16. No history of intolerance, hypersensitivity, or reaction to any food or food
             ingredient

         17. Able to continue a gluten-free diet for the duration of the study

        Exclusion Criteria:

        Part 1, Part 2, Part 3, and Part 4

          1. Current symptoms or signs of illness

          2. Chronic viral infection or immunodeficiency condition

          3. Any female who is pregnant, planning to become pregnant during the study, or
             breast-feeding; any male who is planning to father a child during the study

          4. Receipt (or planned receipt) of another investigational medication within 4 weeks
             prior to the Screening Visit through the duration of the study

          5. Alcohol consumption greater than (>) 5 drinks/week, alcohol consumption within 72
             hours prior to any study visit (Part 1, Part 2, and Part 3), alcohol consumption
             within 72 hours prior to Day 1 of the first Cohort Treatment Period through the Safety
             Visit (Part 4), or a positive alcohol breathalyzer test at any study visit

          6. History of illicit or recreational drug use within the three years prior to the
             Screening Visit, or a positive urine drug screen at any study visit

          7. Use of tobacco or nicotine products, including smoking, smokeless tobacco,
             e-cigarettes, or nicotine replacement products within 12 months prior to the Screening
             Visit through the duration of the study