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

NCT ID: NCT03701555

Last Updated: 2023-04-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

139 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-19

Study Completion Date

2021-07-02

Brief Summary

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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

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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.

Conditions

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Digestive System Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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

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.

Group Type EXPERIMENTAL

PvP001 placebo

Intervention Type OTHER

placebo

PvP001 100 mg

Intervention Type DRUG

PvP001 100 mg

PvP001 300 mg

Intervention Type DRUG

PvP001 300 mg

PvP001 900 mg

Intervention Type DRUG

PvP001 900 mg

Part 1, Cohort 1E-1 Healthy Participants

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

Group Type EXPERIMENTAL

Maximum Feasible Dose (MFD) of PvP002

Intervention Type DRUG

MFD of PvP002

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

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.

Group Type EXPERIMENTAL

PvP001 placebo

Intervention Type OTHER

placebo

PvP001 100 mg

Intervention Type DRUG

PvP001 100 mg

PvP001 300 mg

Intervention Type DRUG

PvP001 300 mg

PvP001 900 mg

Intervention Type DRUG

PvP001 900 mg

Part 1, Cohort 1E-2 CeD

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

Group Type EXPERIMENTAL

Maximum Feasible Dose (MFD) of PvP002

Intervention Type DRUG

MFD of PvP002

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

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.

Group Type EXPERIMENTAL

PvP001 placebo

Intervention Type OTHER

placebo

Maximum Tolerated Dose (MTD) of PvP001

Intervention Type DRUG

Maximum Tolerated Dose (MTD) of PvP001

MTD of PvP001 following 7 days of PPI treatment

Intervention Type DRUG

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

Part 2, Cohort 2D Healthy Participants

Participants will receive PvP001 placebo or MFD of PvP001.

Group Type EXPERIMENTAL

PvP001 placebo

Intervention Type OTHER

placebo

Maximum Tolerated Dose (MTD) of PvP001

Intervention Type DRUG

Maximum Tolerated Dose (MTD) of PvP001

Part 2, Cohort 2E Healthy Participants

Participants will receive PvP002 placebo or MFD of PvP002.

Group Type EXPERIMENTAL

Maximum Feasible Dose (MFD) of PvP002

Intervention Type DRUG

MFD of PvP002

PvP002 placebo

Intervention Type OTHER

Placebo

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

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

Group Type EXPERIMENTAL

PvP001 placebo

Intervention Type OTHER

placebo

PvP001 300 mg

Intervention Type DRUG

PvP001 300 mg

PvP001 600 mg

Intervention Type DRUG

PvP001 600 mg

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

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

Group Type EXPERIMENTAL

PvP001 placebo

Intervention Type OTHER

placebo

PvP001 900 mg

Intervention Type DRUG

PvP001 900 mg

Part 3, Cohorts 3A and 3B Healthy Participants

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.

Group Type EXPERIMENTAL

PvP003 placebo

Intervention Type DRUG

Placebo tablet orally.

PvP003

Intervention Type DRUG

PvP003 tablet orally.

Part 3, Cohorts 3C and 3D Healthy Participants

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.

Group Type EXPERIMENTAL

PvP003 placebo

Intervention Type DRUG

Placebo tablet orally.

PvP003

Intervention Type DRUG

PvP003 tablet orally.

Part 3, Cohorts 3E and 3F Healthy Participants

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.

Group Type EXPERIMENTAL

PvP003 placebo

Intervention Type DRUG

Placebo tablet orally.

PvP003

Intervention Type DRUG

PvP003 tablet orally.

Part 3, Cohorts 3G and 3H Healthy Participants

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.

Group Type EXPERIMENTAL

PvP003 placebo

Intervention Type DRUG

Placebo tablet orally.

PvP003

Intervention Type DRUG

PvP003 tablet orally.

Part 4, Cohorts 4A and 4B Healthy Participants

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

Group Type EXPERIMENTAL

PvP003 placebo

Intervention Type DRUG

Placebo tablet orally.

PvP003

Intervention Type DRUG

PvP003 tablet orally.

Part 3, Cohorts 3I and 3J Healthy Participants

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.

Group Type EXPERIMENTAL

PvP003 placebo

Intervention Type DRUG

Placebo tablet orally.

PvP003 150 mg

Intervention Type DRUG

PvP003 150 mg

Interventions

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PvP001 placebo

placebo

Intervention Type OTHER

PvP001 100 mg

PvP001 100 mg

Intervention Type DRUG

PvP001 300 mg

PvP001 300 mg

Intervention Type DRUG

PvP001 900 mg

PvP001 900 mg

Intervention Type DRUG

Maximum Feasible Dose (MFD) of PvP002

MFD of PvP002

Intervention Type DRUG

Maximum Tolerated Dose (MTD) of PvP001

Maximum Tolerated Dose (MTD) of PvP001

Intervention Type DRUG

MTD of PvP001 following 7 days of PPI treatment

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

Intervention Type DRUG

PvP002 placebo

Placebo

Intervention Type OTHER

PvP001 600 mg

PvP001 600 mg

Intervention Type DRUG

PvP003 placebo

Placebo tablet orally.

Intervention Type DRUG

PvP003

PvP003 tablet orally.

Intervention Type DRUG

PvP003 150 mg

PvP003 150 mg

Intervention Type DRUG

Other Intervention Names

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MFD of PvP002

Eligibility Criteria

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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

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)

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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Anaheim Clinical Trials

Anaheim, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33741317 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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PvP-102-01

Identifier Type: -

Identifier Source: org_study_id

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