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Assess the Safety, Tolerability, Pharmacokinetics (PK), and Gluten Degradation Activity of PvP001, PvP002, and PvP003 in Healthy Adult Volunteers and to Assess the Safety, Tolerability, and PK of PvP001 and PvP002 in Adults With Celiac Disease (CeD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03701555
Recruitment Status : Recruiting
First Posted : October 10, 2018
Last Update Posted : June 11, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of the study is to determine the safety and tolerability of single doses of PvP001 and PvP002, in healthy volunteers and participants with CeD in Part 1, to evaluate the ability of PvP001 and PvP002 to degrade gluten in healthy volunteers and to determine the effect of standard dose proton pump inhibitor (PPI) pretreatment on the ability of PvP001 to degrade gluten in healthy volunteers in Part 2, to evaluate the ability of PvP003 to degrade gluten in healthy volunteers in Part 3, and to determine the safety and tolerability of multiple doses of PvP003 600 milligram (mg), in healthy volunteers in Part 4.

Condition or disease Intervention/treatment Phase
Digestive System Disease Other: PvP001 placebo Drug: 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 Other: PvP002 placebo Drug: PvP001 600 mg Drug: PvP003 placebo Drug: PvP003 Phase 1

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 four groups; within Groups 1 to 4 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 the treatment order. A participant may participate in only one part/group of the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
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
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Experimental: 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.
Other: PvP001 placebo
placebo

Drug: PvP001 100 mg
PvP001 100 mg

Drug: PvP001 300 mg
PvP001 300 mg

Drug: PvP001 900 mg
PvP001 900 mg

Experimental: 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.
Drug: Maximum Feasible Dose (MFD) of PvP002
Maximum Feasible Dose (MFD) of PvP002

Experimental: 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.
Other: PvP001 placebo
placebo

Drug: PvP001 100 mg
PvP001 100 mg

Drug: PvP001 300 mg
PvP001 300 mg

Drug: PvP001 900 mg
PvP001 900 mg

Experimental: Part 1, Cohort 1E-2 Celiac Disease (CeD)
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
Maximum Feasible Dose (MFD) of PvP002

Experimental: 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.
Other: PvP001 placebo
placebo

Drug: Maximum Tolerated Dose (MTD) of PvP001
Maximum Tolerated Dose (MTD) of PvP001

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

Experimental: Part 2, Cohort 2D Healthy Participants
Participants will receive PvP001 placebo or MFD of PvP001.
Other: PvP001 placebo
placebo

Drug: Maximum Tolerated Dose (MTD) of PvP001
Maximum Tolerated Dose (MTD) of PvP001

Experimental: Part 2, Cohort 2E Healthy Participants
Participants will receive PvP002 placebo or MFD of PvP002.
Drug: Maximum Feasible Dose (MFD) of PvP002
Maximum Feasible Dose (MFD) of PvP002

Other: PvP002 placebo
Placebo

Experimental: Part 2, Cohort 2F- Cohort 2H Healthy Participants
Participants will receive the PvP001 placebo and either 300 mg or 600 mg of PvP001.
Other: PvP001 placebo
placebo

Drug: PvP001 300 mg
PvP001 300 mg

Drug: PvP001 600 mg
PvP001 600 mg

Experimental: Part 2, Cohort 2I and Cohort 2J Healthy Participants
Participants will receive the PvP001 placebo and 900 mg of PvP001.
Other: PvP001 placebo
placebo

Drug: PvP001 900 mg
PvP001 900 mg

Experimental: 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.
Drug: PvP003 placebo
Placebo tablet orally.

Drug: PvP003
PvP003 tablet orally.

Experimental: 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.
Drug: PvP003 placebo
Placebo tablet orally.

Drug: PvP003
PvP003 tablet orally.

Experimental: 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.
Drug: PvP003 placebo
Placebo tablet orally.

Drug: PvP003
PvP003 tablet orally.

Experimental: 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.
Drug: PvP003 placebo
Placebo tablet orally.

Drug: PvP003
PvP003 tablet orally.

Experimental: Part 4, Cohorts 4A and 4B Healthy Participants
Participants will receive multiple dose of PvP003 placebo and 600 mg of PvP003.
Drug: PvP003 placebo
Placebo tablet orally.

Drug: PvP003
PvP003 tablet orally.




Primary Outcome Measures :
  1. Part 1 and Part 4: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 in Part 1 and PvP003 600 mg After Multiple Doses in Part 4 [ Time Frame: Part 1: up to 4 weeks; Part 4: up to 6 weeks ]
  2. Part 1 and Part 4: Number of Participants Reporting one or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 in Part 1 and PvP003 600 mg After Multiple Doses in Part 4 [ Time Frame: Part 1: up to 4 weeks; Part 4: up to 6 weeks ]
  3. Part 1 and Part 4: Number of Participants with Markedly Abnormal Laboratory Values for PvP001 and PvP002 in Part 1 and PvP003 600 mg After Multiple Doses in Part 4 [ Time Frame: Part 1: up to 4 weeks; Part 4: up to 6 weeks ]
  4. Part 1 and Part 4: Number of Participants with Clinically Significant Change from Baseline Electrocardiogram's (ECG's) Findings for PvP001 and PvP002 in Part 1 and PvP003 600 mg After Multiple Doses in Part 4 [ Time Frame: Part 1: up to 4 weeks; Part 4: up to 6 weeks ]
  5. Part 1 and Part 4: Number of Participants with Clinically Significant Change from Baseline in Vital Signs Values for PvP001 and PvP002 in Part 1 and PvP003 600 mg After Multiple Doses in Part 4 [ Time Frame: Part 1: up to 4 weeks; Part 4: up to 6 weeks ]
  6. Part 1 and Part 4: Number of Participants with Clinically Significant Change from Baseline in Physical Examination Findings for PvP001 and PvP002 in Part 1 and PvP003 600 mg After Multiple Doses in Part 4 [ Time Frame: Part 1: up to 4 weeks; Part 4: up to 6 weeks ]
  7. Part 2: Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP001 [ Time Frame: Day 1 ]
  8. Part 2: Percentage of Gluten Degradation by PvP002 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP002 [ Time Frame: Day 1 ]
  9. Part 2: Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal Following 7 days of Standard Dose PPI (Proton Pump Inhibitor) Treatment [ Time Frame: Up to 7 days ]
  10. Part 2: Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal After Administration of PvP001 [ Time Frame: Day 1: up to 65 minutes post-dose ]
  11. Part 2: Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 1 gm Gluten-containing Study Meal After Administration of PvP001 [ Time Frame: Day 1: up to 65 minutes post-dose ]
  12. Part 3: Percentage of Gluten Degradation by PvP003 600 mg in a Standardized 1 gm Gluten-containing Study Meal After Administration of PvP003 [ Time Frame: Day 1 ]

Secondary Outcome Measures :
  1. Part 1 and Part 2; Cmax: Maximum Observed Plasma Concentration for PvP001 and PvP002 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post-dose ]
  2. Part 1 and Part 2; Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP001 and PvP002 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post-dose ]
  3. Part 1 and Part 2; T(1/2): Terminal Disposition Phase Half-life of PvP001 and PvP002 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post-dose ]
  4. Part 1 and Part 2; AUC: Area Under the Plasma Concentration Versus Time Curve of PvP001 and PvP002 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post-dose ]
  5. Part 1 and Part 2: Number of Participants with Anti-drug Antibodies (ADA ) to PvP001 and PvP002 [ Time Frame: 28 days ]
  6. Part 1: Maximum Tolerated Dose (MTD) of PvP001 for use in Part 2 of the Study [ Time Frame: 28 days ]
  7. Part 2: Number of Participants Reporting one or More TEAEs for PvP001 and PvP002 [ Time Frame: Up to 6 weeks ]
  8. Part 2: Number of Participants Reporting TESAEs for PvP001 and PvP002 [ Time Frame: Up to 6 weeks ]
  9. Part 2: Number of Participants with Markedly Abnormal Laboratory Values for PvP001 and PvP002 [ Time Frame: Up to 6 weeks ]
  10. Part 2: Number of Participants with Clinically Significant Change from Baseline in ECG's Findings for PvP001 and PvP002 [ Time Frame: Up to 6 weeks ]
  11. Part 2: Number of Participants with Clinically Significant Change from Baseline in Vital Signs Values for PvP001 and PvP002 [ Time Frame: Up to 6 weeks ]
  12. Part 2: Number of Participants with Clinically Significant Change from Baseline in Physical Examination Findings for PvP001 and PvP002 [ Time Frame: Up to 6 weeks ]
  13. Part 3: Percentage of Gluten Degradation by PvP003 600 mg With and Without Pretreatment Buffer Solution Administered Before a Standardized 1 gm Gluten-containing Study Meal [ Time Frame: Day 1: 35 and 65 minutes post-dose ]
  14. Part 3: Percentage of Gluten Degradation by PvP003 600 mg Without Pretreatment Buffer Solution Administered After an Approximately 50 Milliliter (mL) Portion of a Standardized 1 gm Gluten-containing Study Meal [ Time Frame: Day 1: 35 and 65 minutes post-dose ]
  15. Part 3: Percentage of Gluten Degradation by PvP003 600 mg Without Pretreatment Buffer Solution Administered Before a Standardized Gluten-free Study Meal Followed by a Standardized 1 gm Gluten-containing Study Meal [ Time Frame: Day 1: 65 minutes post-dose ]
  16. Part 3: Number of Participants Reporting one or More TEAEs with PvP003 600 mg After a Single Dose [ Time Frame: Up to 5 weeks ]
  17. Part 3: Number of Participants Reporting TESAE with PvP003 600 mg After a Single Dose [ Time Frame: Up to 5 weeks ]
  18. Part 3: Number of Participants with Markedly Abnormal Clinically Significant Changes in Laboratory Values Abnormalities Findings for with PvP003 600 mg After a Single Dose [ Time Frame: Up to 5 weeks ]
  19. Part 3: Number of Participants with Clinically Significant Change from BaselineChanges in ECG's with PvP003 600 mg After a Single Dose [ Time Frame: Up to 5 weeks ]
  20. Part 3: Number of Participants with Clinically Significant Change from Baseline in n Vital Signs with PvP003 600 mg After a Single Dose [ Time Frame: Up to 5 weeks ]
  21. Part 3: Number of Participants with Clinically Significant Changes in Physical Examination Findings with PvP003 600 mg After a Single Dose [ Time Frame: Up to 5 weeks ]
  22. Part 3; Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Single Dose [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post dose ]
  23. Part 3; Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Single Dose [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post dose ]
  24. Part 3; T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Single Dose [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post dose ]
  25. Part 3, AUC: Area Under the Plasma Concentration Versus Time Curve for PvP003 600 mg single Dose [ Time Frame: Day 1 pre-dose and at multiple time points (up to 480 minutes) post dose ]
  26. Part 3: Number of Participants with ADA to PvP003 600 mg Single Dose [ Time Frame: 28 days ]
  27. Part 4; Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Multiple Dose [ Time Frame: Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose ]
  28. Part 4; Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Multiple Dose [ Time Frame: Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose ]
  29. Part 4; T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Multiple Dose [ Time Frame: Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose ]
  30. Part 4, AUC: Area Under the Plasma Concentration Versus Time Curve for PvP003 600 mg Multiple Dose [ Time Frame: Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose ]
  31. Part 4: Number of Participants with ADA to PvP003 600 mg Multiple Dose [ Time Frame: 28 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 Anti-Drug Antibody Blood Sampling Visit
  5. A male participant must agree to 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

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

  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)

    Additional Inclusion Criteria for Part 1 Participants with Celiac Disease

  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03701555


Contacts
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Contact: Takeda Study Registration Call Center 1-877-825-3327 medicalinformation@tpna.com

Locations
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United States, California
Anaheim Clinical Trials Recruiting
Anaheim, California, United States, 92801
Contact: Peter Winkle, MD    714-774-7777    pwinkle@agmg.com   
Sponsors and Collaborators
Takeda
Investigators
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Principal Investigator: Peter Winkle, MD Anaheim Clinical Trials
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03701555    
Other Study ID Numbers: PvP-102-01
First Posted: October 10, 2018    Key Record Dates
Last Update Posted: June 11, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Celiac Disease
Gastrointestinal Diseases
Digestive System Diseases
Malabsorption Syndromes
Intestinal Diseases
Metabolic Diseases