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
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      This study has four parts. Each part of the study begins with a Screening Period of up to 4
      weeks to allow for completion of screening procedures and subject scheduling. Each
      participant will be screened by means of medical history, medication review, Gastrointestinal
      Symptoms Questionnaire (GSQ), physical examination, vital signs, weight, height, laboratory
      tests, and ECG. The GSQ is being used as a separate safety monitoring tool in this study to
      ensure that all gastrointestinal complaints are reported by the participant.

      Following completion of all screening procedures, eligible participants will be enrolled in
      the study.

      Part 1 of the study in healthy participants will be completed prior to enrollment of any
      subject in Part 2 of the study. A participant enrolled in Part 1 of the study will
      participate in one of five dose Cohorts. Enrollment of healthy participants and participants
      with CeD in each of the five dose Cohorts will occur sequentially, but each of these dose
      Cohorts will be open to enrollment only after demonstration of the safety and tolerability of
      the same dose level in healthy participants. A healthy participant enrolled in Part 2 of the
      study will participate in one of three groups; within Groups 1, 2 and 3 enrollment may occur
      in parallel. A healthy participant enrolled in Part 3 of the study will participate in one of
      five groups; within Groups 1 to 5 enrollment will occur sequentially. A healthy participant
      enrolled in Part 4 of the study will participate in two cohorts; enrollment in Part 4 may
      occur in parallel with enrollment in Part 3. Each participant will be randomized to one of
      two possible treatment order. Participants who participate in Part 1 or Part 2 of the study,
      and who are not ADA positive, may participate in Part 3 or Part 4 of the study. No other
      participants may participate in more than one Part/Group of the study.
    

Intervention name(s): 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 type(s): Other; Drug; Drug; Drug; Drug; Drug; Drug; Other; Drug; Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): MFD of PvP002
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Primary purpose: Basic Science