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

NCT03701555 | Completed Phase 1 Results FDA Drug

• 1 other identifier: PvP-102-01
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 1

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.

Conditions

Digestive System Disease

Outcome Measures

Primary Outcomes (15)

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

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

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

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

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

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

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

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

• 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.

  Cohort Treatment Day

• 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.

  Cohort Treatment Day

• 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.

  Cohort Treatment Day

• 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.

  Cohort Treatment Day: at 20 minutes post-dose

• 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.

  Cohort Treatment Day: at 35 minutes post-dose

• 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.

  Cohort Treatment Day: at 65 minutes post-dose

• 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.

  Cohort Treatment Day: at 20 minutes post-dose

• 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.

  Cohort Treatment Day: at 35 minutes post-dose

• 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.

  Cohort Treatment Day: at 65 minutes post-dose

• 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.

  Cohort Treatment Day: at 35 minutes

• 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.

  Cohort Treatment Day: at 65 minutes

Secondary Outcomes (21)

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

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

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

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

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

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

• 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

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

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

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

Study Arms (15)

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

EXPERIMENTAL

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.

Other: PvP001 placebo; Drug: PvP001 100 mg; Drug: PvP001 300 mg; Drug: PvP001 900 mg

Part 1, Cohort 1E-1 Healthy Participants

EXPERIMENTAL

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

Drug: Maximum Feasible Dose (MFD) of PvP002

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

EXPERIMENTAL

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.

Other: PvP001 placebo; Drug: PvP001 100 mg; Drug: PvP001 300 mg; Drug: PvP001 900 mg

Part 1, Cohort 1E-2 CeD

EXPERIMENTAL

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

Drug: Maximum Feasible Dose (MFD) of PvP002

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

EXPERIMENTAL

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.

Other: PvP001 placebo; Drug: Maximum Tolerated Dose (MTD) of PvP001; Drug: MTD of PvP001 following 7 days of PPI treatment

Part 2, Cohort 2D Healthy Participants

EXPERIMENTAL

Participants will receive PvP001 placebo or MFD of PvP001.

Other: PvP001 placebo; Drug: Maximum Tolerated Dose (MTD) of PvP001

Part 2, Cohort 2E Healthy Participants

EXPERIMENTAL

Participants will receive PvP002 placebo or MFD of PvP002.

Drug: Maximum Feasible Dose (MFD) of PvP002; Other: PvP002 placebo

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

EXPERIMENTAL

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

Other: PvP001 placebo; Drug: PvP001 300 mg; Drug: PvP001 600 mg

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

EXPERIMENTAL

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

Other: PvP001 placebo; Drug: PvP001 900 mg

Part 3, Cohorts 3A and 3B Healthy Participants

EXPERIMENTAL

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.

Drug: PvP003 placebo; Drug: PvP003

Part 3, Cohorts 3C and 3D Healthy Participants

EXPERIMENTAL

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.

Drug: PvP003 placebo; Drug: PvP003

Part 3, Cohorts 3E and 3F Healthy Participants

EXPERIMENTAL

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.

Drug: PvP003 placebo; Drug: PvP003

Part 3, Cohorts 3G and 3H Healthy Participants

EXPERIMENTAL

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.

Drug: PvP003 placebo; Drug: PvP003

Part 4, Cohorts 4A and 4B Healthy Participants

EXPERIMENTAL

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

Drug: PvP003 placebo; Drug: PvP003

Part 3, Cohorts 3I and 3J Healthy Participants

EXPERIMENTAL

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.

Drug: PvP003 placebo; Drug: PvP003 150 mg

Interventions

PvP001 placebo OTHER

placebo

Part 1, Cohort 1A-1 to 1D-1 Healthy Participants; Part 1, Cohort 1A-2 - 1D-2 Celiac Disease (CeD); Part 2, Cohort 2A - Cohort 2C Healthy Participants; Part 2, Cohort 2D Healthy Participants; Part 2, Cohort 2F- Cohort 2H Healthy Participants; Part 2, Cohort 2I and Cohort 2J Healthy Participants

PvP001 100 mg DRUG

PvP001 100 mg

Part 1, Cohort 1A-1 to 1D-1 Healthy Participants; Part 1, Cohort 1A-2 - 1D-2 Celiac Disease (CeD)

PvP001 300 mg DRUG

PvP001 300 mg

Part 1, Cohort 1A-1 to 1D-1 Healthy Participants; Part 1, Cohort 1A-2 - 1D-2 Celiac Disease (CeD); Part 2, Cohort 2F- Cohort 2H Healthy Participants

PvP001 900 mg DRUG

PvP001 900 mg

Part 1, Cohort 1A-1 to 1D-1 Healthy Participants; Part 1, Cohort 1A-2 - 1D-2 Celiac Disease (CeD); Part 2, Cohort 2I and Cohort 2J Healthy Participants

Maximum Feasible Dose (MFD) of PvP002 DRUG

MFD of PvP002

Also known as: MFD of PvP002

Part 1, Cohort 1E-1 Healthy Participants; Part 1, Cohort 1E-2 CeD; Part 2, Cohort 2E Healthy Participants

Maximum Tolerated Dose (MTD) of PvP001 DRUG

Maximum Tolerated Dose (MTD) of PvP001

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

MTD of PvP001 following 7 days of PPI treatment DRUG

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

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

PvP002 placebo OTHER

Placebo

Part 2, Cohort 2E Healthy Participants

PvP001 600 mg DRUG

PvP001 600 mg

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

PvP003 placebo DRUG

Placebo tablet orally.

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 3, Cohorts 3I and 3J Healthy Participants; Part 4, Cohorts 4A and 4B Healthy Participants

PvP003 DRUG

PvP003 tablet orally.

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

PvP003 150 mg DRUG

PvP003 150 mg

Part 3, Cohorts 3I and 3J Healthy Participants

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Related Publications (1)

• 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.

  PMID: 33741317 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Digestive System Diseases

Interventions

Maximum Tolerated Dose

Intervention Hierarchy (Ancestors)

Toxicity Tests; Investigative Techniques; Toxicological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 10, 2018
• Study Start: June 19, 2018
• Primary Completion: January 31, 2021
• Study Completion: July 2, 2021
• Last Updated: April 4, 2023
• Results First Posted: April 4, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

US (1)