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

Primary Purpose

Digestive System Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

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

About this trial

This is an interventional basic science trial for Digestive System Disease

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Anaheim Clinical Trials

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Arm Label

Part 1, Cohort 1A-1 to 1D-1 Healthy Participants

Part 1, Cohort 1E-1 Healthy Participants

Part 1, Cohort 1A-2 - 1D-2 Celiac Disease (CeD)

Part 1, Cohort 1E-2 CeD

Part 2, Cohort 2A - Cohort 2C Healthy Participants

Part 2, Cohort 2D Healthy Participants

Part 2, Cohort 2E Healthy Participants

Part 2, Cohort 2F- Cohort 2H Healthy Participants

Part 2, Cohort 2I and Cohort 2J Healthy Participants

Part 3, Cohorts 3A and 3B Healthy Participants

Part 3, Cohorts 3C and 3D Healthy Participants

Part 3, Cohorts 3E and 3F Healthy Participants

Part 3, Cohorts 3G and 3H Healthy Participants

Part 4, Cohorts 4A and 4B Healthy Participants

Part 3, Cohorts 3I and 3J Healthy Participants

Arm Description

A single dose of PvP001 placebo, PvP001 100 mg, PvP001 300 mg, or PvP001 900 mg will be administered in ascending order to healthy participants in Cohorts 1A-1, 1B-1, 1C-1, and 1D-1.

A single dose of the maximum feasible dose (MFD) of PvP002 will then be administered to healthy participants in Cohort 1E-1.

A single dose of PvP001 placebo, PvP001 100 mg, PvP001 300 mg, or PvP001 900 mg will be administered in ascending order to participants with CeD in Cohorts 1A-2, 1B-2, 1C-2, and 1D-2.

A single dose of the MFD of PvP002 will then be administered to participants with CeD in Cohort 1E-2.

Participants will be blinded to the PvP001 dose (placebo or MTD of PvP001) and will also receive MTD of PvP001 following 7 days of PPI treatment.

Participants will receive PvP001 placebo or MFD of PvP001.

Participants will receive PvP002 placebo or MFD of PvP002.

Participants will receive the PvP001 placebo and either 300 mg or 600 mg of PvP001.

Participants will receive the PvP001 placebo and 900 mg of PvP001.

Participants will receive single dose of PvP003 placebo and 600 mg of PvP003 with pretreatment buffer solution before a standardized 1 gm gluten-containing study meal.

Participants will receive single dose of PvP003 placebo and 600 mg of PvP003 without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal.

Participants will receive single dose of PvP003 placebo and 600 mg of PvP003 without pretreatment buffer solution after an approximately 50 milliliter (mL) portion of a standardized 1 gm gluten-containing study meal.

Participants will receive single dose of PvP003 placebo and 600 mg of PvP003 without pretreatment buffer solution before a standardized gluten-free study meal followed approximately 30 minutes later by a standardized 1 gm gluten-containing study meal.

Participants will receive multiple dose of PvP003 placebo and 600 mg of PvP003.

Participants will receive single dose of PvP003 placebo and 150 mg of PvP003 without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal.

Outcomes

Primary Outcome Measures

Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002

Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses

Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002

Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using Enzyme-Linked Immunosorbent Assay (ELISA) based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

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

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Secondary Outcome Measures

Part 1 and Part 2, Cmax: Maximum Observed Plasma Concentration for PvP001 and PvP002

Part 1 and Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP001 and PvP002

Part 1 and Part 2, T(1/2): Terminal Disposition Phase Half-life of PvP001 and PvP002

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

Part 1 and Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP001 and PvP002

Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002

Part 1: Maximum Tolerated Dose (MTD) of PvP001

MTD was defined as the maximum dose that was determined to be safe and tolerable for Part 1 (1B-1 and 1B-2, 1C-1 and 1C-2, 1D-1 and 1D-2) in healthy or CeD participants.

Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002

Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose

Part 3, Cmax: Maximum Observed Plasma Concentration for PvP003 150 mg and 600 mg Single Dose

Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 150 mg and 600 mg Single Dose

Part 3, T(1/2): Terminal Disposition Phase Half-life of PvP003 150 mg and 600 mg Single Dose

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

Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 150 mg and 600 mg Single Dose

Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose

Part 4, Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Multiple Dose

Part 4, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Multiple Dose

Part 4, T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Multiple Dose

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

Part 4, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 600 mg Multiple Dose

Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose

Full Information

NCT ID

NCT03701555

First Posted

October 8, 2018

Last Updated

June 21, 2022

Sponsor

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03701555

Brief Title

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

Official Title

A Phase 1, Four-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Gluten Degradation Activity of PvP001, PvP002, and PvP003 in Healthy Adult Volunteers and to Assess the Safety, Tolerability, and Pharmacokinetics of PvP001 and PvP002 in Adults With Celiac Disease

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

June 19, 2018 (Actual)

Primary Completion Date

January 31, 2021 (Actual)

Study Completion Date

July 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Millennium Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Digestive System Disease

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

Participant

Allocation

Randomized

Enrollment

139 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1, Cohort 1A-1 to 1D-1 Healthy Participants

Arm Type

Experimental

Arm Description

A single dose of PvP001 placebo, PvP001 100 mg, PvP001 300 mg, or PvP001 900 mg will be administered in ascending order to healthy participants in Cohorts 1A-1, 1B-1, 1C-1, and 1D-1.

Arm Title

Part 1, Cohort 1E-1 Healthy Participants

Arm Type

Experimental

Arm Description

A single dose of the maximum feasible dose (MFD) of PvP002 will then be administered to healthy participants in Cohort 1E-1.

Arm Title

Part 1, Cohort 1A-2 - 1D-2 Celiac Disease (CeD)

Arm Type

Experimental

Arm Description

A single dose of PvP001 placebo, PvP001 100 mg, PvP001 300 mg, or PvP001 900 mg will be administered in ascending order to participants with CeD in Cohorts 1A-2, 1B-2, 1C-2, and 1D-2.

Arm Title

Part 1, Cohort 1E-2 CeD

Arm Type

Experimental

Arm Description

A single dose of the MFD of PvP002 will then be administered to participants with CeD in Cohort 1E-2.

Arm Title

Part 2, Cohort 2A - Cohort 2C Healthy Participants

Arm Type

Experimental

Arm Description

Participants will be blinded to the PvP001 dose (placebo or MTD of PvP001) and will also receive MTD of PvP001 following 7 days of PPI treatment.

Arm Title

Part 2, Cohort 2D Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive PvP001 placebo or MFD of PvP001.

Arm Title

Part 2, Cohort 2E Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive PvP002 placebo or MFD of PvP002.

Arm Title

Part 2, Cohort 2F- Cohort 2H Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive the PvP001 placebo and either 300 mg or 600 mg of PvP001.

Arm Title

Part 2, Cohort 2I and Cohort 2J Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive the PvP001 placebo and 900 mg of PvP001.

Arm Title

Part 3, Cohorts 3A and 3B Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive single dose of PvP003 placebo and 600 mg of PvP003 with pretreatment buffer solution before a standardized 1 gm gluten-containing study meal.

Arm Title

Part 3, Cohorts 3C and 3D Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive single dose of PvP003 placebo and 600 mg of PvP003 without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal.

Arm Title

Part 3, Cohorts 3E and 3F Healthy Participants

Arm Type

Experimental

Arm Description

Arm Title

Part 3, Cohorts 3G and 3H Healthy Participants

Arm Type

Experimental

Arm Description

Arm Title

Part 4, Cohorts 4A and 4B Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive multiple dose of PvP003 placebo and 600 mg of PvP003.

Arm Title

Part 3, Cohorts 3I and 3J Healthy Participants

Arm Type

Experimental

Arm Description

Participants will receive single dose of PvP003 placebo and 150 mg of PvP003 without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal.

Intervention Type

Other

Intervention Name(s)

PvP001 placebo

Intervention Description

placebo

Intervention Type

Drug

Intervention Name(s)

PvP001 100 mg

Intervention Description

PvP001 100 mg

Intervention Type

Drug

Intervention Name(s)

PvP001 300 mg

Intervention Description

PvP001 300 mg

Intervention Type

Drug

Intervention Name(s)

PvP001 900 mg

Intervention Description

PvP001 900 mg

Intervention Type

Drug

Intervention Name(s)

Maximum Feasible Dose (MFD) of PvP002

Other Intervention Name(s)

MFD of PvP002

Intervention Description

MFD of PvP002

Intervention Type

Drug

Intervention Name(s)

Maximum Tolerated Dose (MTD) of PvP001

Intervention Description

Maximum Tolerated Dose (MTD) of PvP001

Intervention Type

Drug

Intervention Name(s)

MTD of PvP001 following 7 days of PPI treatment

Intervention Description

Maximum Tolerated Dose (MTD) of PvP001 following 7 days of PPI (Proton Pump Inhibitor) treatment

Intervention Type

Other

Intervention Name(s)

PvP002 placebo

Intervention Description

Placebo

Intervention Type

Drug

Intervention Name(s)

PvP001 600 mg

Intervention Description

PvP001 600 mg

Intervention Type

Drug

Intervention Name(s)

PvP003 placebo

Intervention Description

Placebo tablet orally.

Intervention Type

Drug

Intervention Name(s)

PvP003

Intervention Description

PvP003 tablet orally.

Intervention Type

Drug

Intervention Name(s)

PvP003 150 mg

Intervention Description

PvP003 150 mg

Primary Outcome Measure Information:

Title

Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002

Time Frame

Cohort Treatment Day up to 5 days after 24-hour safety assessment on Day 2 (up to Day 7)

Title

Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses

Time Frame

Day 1 of Cohort Treatment Period 1 up to 5 days after the Day 5 of Cohort Treatment Period 2 (up to Day 28)

Title

Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002

Time Frame

Cohort Treatment Day up to 5 days after 24-hour safety assessment on Day 2 (up to Day 7)

Title

Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses

Time Frame

Day 1 of Cohort Treatment Period 1 up to 5 days after the Day 5 of Cohort Treatment Period 2 (up to Day 28)

Title

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

Description

Time Frame

Cohort Treatment Day

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 20 minutes post-dose

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 35 minutes post-dose

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 65 minutes post-dose

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 20 minutes post-dose

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 35 minutes post-dose

Title

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

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 65 minutes post-dose

Title

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 35 minutes

Title

Description

Median percentage degraded relative to placebo was derived using the formula: (1 - [active/placebo])*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.

Time Frame

Cohort Treatment Day: at 65 minutes

Secondary Outcome Measure Information:

Title

Part 1 and Part 2, Cmax: Maximum Observed Plasma Concentration for PvP001 and PvP002

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose

Title

Part 1 and Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP001 and PvP002

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose

Title

Part 1 and Part 2, T(1/2): Terminal Disposition Phase Half-life of PvP001 and PvP002

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose

Title

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

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose

Title

Part 1 and Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP001 and PvP002

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose

Title

Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002

Time Frame

At Day 14 and Day 28

Title

Part 1: Maximum Tolerated Dose (MTD) of PvP001

Description

MTD was defined as the maximum dose that was determined to be safe and tolerable for Part 1 (1B-1 and 1B-2, 1C-1 and 1C-2, 1D-1 and 1D-2) in healthy or CeD participants.

Time Frame

Cohort Treatment Day up to Day 7

Title

Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002

Time Frame

Cohort Treatment Day up to 5 days after the final Cohort Treatment Day (up to Day 22)

Title

Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose

Time Frame

Cohort Treatment Day up to 5 days after final Cohort Treatment Day (up to Day 10)

Title

Part 3, Cmax: Maximum Observed Plasma Concentration for PvP003 150 mg and 600 mg Single Dose

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose

Title

Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 150 mg and 600 mg Single Dose

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose

Title

Part 3, T(1/2): Terminal Disposition Phase Half-life of PvP003 150 mg and 600 mg Single Dose

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose

Title

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

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose

Title

Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 150 mg and 600 mg Single Dose

Time Frame

Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose

Title

Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose

Time Frame

At Day 14 and Day 28

Title

Part 4, Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Multiple Dose

Time Frame

Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose

Title

Part 4, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Multiple Dose

Time Frame

Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose

Title

Part 4, T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Multiple Dose

Time Frame

Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose

Title

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

Time Frame

Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose

Title

Part 4, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 600 mg Multiple Dose

Time Frame

Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose

Title

Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose

Time Frame

At Day 14 and Day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Anaheim Clinical Trials

City

Anaheim

State/Province

California

ZIP/Postal Code

92801

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD Sharing Access Criteria

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

IPD Sharing URL

https://vivli.org/ourmember/takeda/

Citations:

PubMed Identifier

33741317

Citation

Pultz IS, Hill M, Vitanza JM, Wolf C, Saaby L, Liu T, Winkle P, Leffler DA. Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019. Epub 2021 Mar 17.

Results Reference

derived

Links:

URL

https://clinicaltrials.takeda.com/study-detail/5fb4db4c17465c002989a1a5

Description

Related Info

Learn more about this trial

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

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