A Study of PVP001, PVP002, and PVP003 in Healthy Adults and PVP001 and PVP002 in Adults With Celiac Disease

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: PvP001 placebo (Other); PvP001 100 mg (Drug); PvP001 300 mg (Drug); PvP001 900 mg (Drug); Maximum Feasible Dose (MFD) of PvP002 (Drug); Maximum Tolerated Dose (MTD) of PvP001 (Drug); MTD of PvP001 following 7 days of PPI treatment (Drug); PvP002 placebo (Other); PvP001 600 mg (Drug); PvP003 placebo (Drug); PvP003 (Drug); PvP003 150 mg (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Millennium Pharmaceuticals, Inc.
Primary completion: Jan 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002	0; 0; 0; 0; 0; 3	—
PRIMARY Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses	0; 0	—
PRIMARY Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002	0; 0; 0; 0; 0; 0	—
PRIMARY Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses	0; 0	—
PRIMARY Part 2, Group 1, Cohort 2B: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 Gram (gm) Gluten-containing Study Meal After Administration of PvP001	94.41; 97.89	—
PRIMARY Part 2, Group 2, Cohort 2E: Median Percentage of Gluten Degradation by PvP002 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP002	99.67; 99.70	—
PRIMARY Part 2, Group 1, Cohort 2C: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal Following 7 Days of Standard Dose PPI Treatment	99.44; 99.62	—
PRIMARY Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001	95.89; 98.13; 97.63; 97.98	—
PRIMARY Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001	98.19; 98.95; 97.92; 98.43	—
PRIMARY Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001	95.21; 98.15; 96.30; 98.87	—
PRIMARY Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001	99.82; 99.77	—
PRIMARY Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001	99.48; 99.69	—
PRIMARY Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001	99.22; 98.49	—
PRIMARY Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003	94.68; 79.69; 68.49; NA; 88.23; 96.66	—
PRIMARY Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003	89.54; 50.36; 85.63; 98.86; 84.48; 95.34	—
SECONDARY Part 1 and Part 2, Cmax: Maximum Observed Plasma Concentration for PvP001 and PvP002	—	—
SECONDARY Part 1 and Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP001 and PvP002	—	—
SECONDARY Part 1 and Part 2, T(1/2): Terminal Disposition Phase Half-life of PvP001 and PvP002	—	—
SECONDARY Part 1 and Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP001 and PvP002	—	—
SECONDARY Part 1 and Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP001 and PvP002	—	—
SECONDARY Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002	0; 0; 0; 0; 0; 0	—
SECONDARY Part 1: Maximum Tolerated Dose (MTD) of PvP001	900	—
SECONDARY Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002	1; 0; 2; 0; 0; 1	—
SECONDARY Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose	4; 1; 0; 0; 1; 1	—
SECONDARY Part 3, Cmax: Maximum Observed Plasma Concentration for PvP003 150 mg and 600 mg Single Dose	—	—
SECONDARY Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 150 mg and 600 mg Single Dose	—	—
SECONDARY Part 3, T(1/2): Terminal Disposition Phase Half-life of PvP003 150 mg and 600 mg Single Dose	—	—
SECONDARY Part 3, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP003 150 mg and 600 mg Single Dose	—	—
SECONDARY Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 150 mg and 600 mg Single Dose	—	—
SECONDARY Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose	0; 0; 0; 0; 0; 0	—
SECONDARY Part 4, Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Multiple Dose	—	—
SECONDARY Part 4, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Multiple Dose	—	—
SECONDARY Part 4, T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Multiple Dose	—	—
SECONDARY Part 4, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP003 600 mg Multiple Dose	—	—
SECONDARY Part 4, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 600 mg Multiple Dose	—	—
SECONDARY Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose	1; 1; 1; 0	—

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

Male or female age 18- 64 years, inclusive
No relevant gastrointestinal symptoms
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).
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
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
Able to read and understand English
Able to provide written informed consent

Additional Inclusion Criteria for Part 1, Part 2, Part 3, and Part 4 Healthy Adult Volunteers

No use of over-the-counter or prescription medication, except for birth control medications for the duration of the study
No history of gastrointestinal diseases or disorders
No history of intolerance, sensitivity, or reactions to gluten or any other food or food ingredient
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

Documented history of Celiac Disease in medical records
Maintaining a gluten-free diet for ≥6 months
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.
No history of gastrointestinal diseases or disorders, other than Celiac Disease
No history of intolerance, hypersensitivity, or reaction to any food or food ingredient
Able to continue a gluten-free diet for the duration of the study

Exclusion Criteria

Part 1, Part 2, Part 3, and Part 4

Current symptoms or signs of illness
Chronic viral infection or immunodeficiency condition
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
Receipt (or planned receipt) of another investigational medication within 4 weeks prior to the Screening Visit through the duration of the study
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
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
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

Bottom Line