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Pharmacokinetics, Safety, and Tolerability of SYN-020

Primary Purpose

Enteritis Caused by Radiation (Disorder)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SYN-020 delayed release capsule
Sponsored by
Theriva Biologics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Enteritis Caused by Radiation (Disorder)

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Subject is able to read, write, and comprehend English at a sufficient level to understand study related materials, has provided written informed consent before any study-related procedure was performed, and is willing and able to comply with all testing and study requirements.
  2. Subject is a healthy male or female, aged 18 through 50 years, inclusive.
  3. Subject does not use any tobacco or nicotine product (eg, cigarette, pipe, e-cigarette, vape) and has not used any tobacco or nicotine product for at least 2 months before Day -1.
  4. Subject has a BMI of 18.5 to 27 kg/m2 for initial cohorts or, for exploratory cohorts, ≥ 27.1 kg/m2. For Cohorts 1 through 4, if insufficient subjects are available to meet this criterion, subjects with a BMI up to 29 kg/m2 may be included with written authorization from the Sponsor.
  5. Subject is healthy based on physical examination, clinical laboratory tests, 12-lead ECG, and vital signs.
  6. Subject is willing to minimize the risk of inducing pregnancy from the time of signing the informed consent form (ICF) to at least either 90 days (males) or 30 days (females) after the study drug dose.
  7. If female, subject has a negative serum pregnancy test at Screening and on Day -1 (CRU admission).
  8. Subject usually has at least 1 bowel movement a day based on self-reporting.

Exclusion Criteria:

  1. Subject has a history or the presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, vascular, metabolic, collagen, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
  2. Subject has any known malabsorption syndrome or history of gastrointestinal surgery that could compromise the study objectives.
  3. Subject has used any medication (prescription or non-prescription) or herbal supplement, other than prescription hormone replacement therapy (eg, thyroid, testosterone, estrogen) or contraception methods described in Inclusion Criterion #6, within 21 days before Day -1.
  4. Subject is pregnant, breastfeeding, or not using a medically accepted method of contraception.
  5. Subject is unable to abstain from artificial sweeteners (eg, aspartame, acesulfame potassium, advantame, saccharin, stevia, and sucralose) from CRU admission to the end of study participation.
  6. Subject has a positive urine drug or alcohol test at Screening or CRU admission OR has a history of drug/alcohol abuse within 12 months before Screening.
  7. Subject has donated more than 500 mL blood during the 3-month period before Day -1.
  8. Subject has known intolerance of study drug/ingredients.
  9. In the judgment of the Investigator, subject has any factor (eg, other treatment) that could invalidate the study result.
  10. Subject is currently enrolled in another clinical study or has received an investigational drug or device within 30 days or within a time period consistent with a washout period of 5 half-lives before signing the ICF, whichever is longer.
  11. Subject has already participated in this study.

Sites / Locations

  • Spaulding Clinical Research LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

SYN-020, 5 mg

SYN-020, 15 mg

SYN-020, 45 mg

SYN-020, 150 mg

Arm Description

6 subjects to receive a single 5 mg dose of SYN-020

6 subjects to receive a single 15 mg dose of SYN-020

6 subjects to receive a single 45 mg dose of SYN-020

6 subjects to receive a single 150 mg dose of SYN-020

Outcomes

Primary Outcome Measures

SYN-020 systemic absorption
Analysis of SYN-020 level present in blood
SYN-020 presence in feces
Analysis of SYN-020 level present in feces

Secondary Outcome Measures

Percentage of Participants with Changes in Clinical Laboratory Testing
Hematology, clinical chemistry, urinalysis, virus serology, drug screen, alcohol screen, pregnancy test, postmenopausal screen
Number of Participants With Changes in Physical exam
Complete and abbreviated physical examinations will be performed
Number of Participants with Changes in Vital Signs
Blood pressure, pulse rate, respiratory rate, oral temperature
Number of Participants with Changes in Electrocardiograms
12-lead ECG, P-wave, QRS-complex, QT-interval
Immunogenicity testing
Measurement of anti-drug antibodies by ELISA

Full Information

First Posted
March 12, 2021
Last Updated
October 7, 2021
Sponsor
Theriva Biologics, Inc.
Collaborators
Spaulding Clinical Research LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04815993
Brief Title
Pharmacokinetics, Safety, and Tolerability of SYN-020
Official Title
A Single Ascending Dose Trial to Assess the Pharmacokinetics, Safety, and Tolerability of Orally Administered SYN-020 Delayed Release Capsules in Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
March 22, 2021 (Actual)
Primary Completion Date
May 18, 2021 (Actual)
Study Completion Date
September 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Theriva Biologics, Inc.
Collaborators
Spaulding Clinical Research LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 1, single-center, open-label, single ascending dose study to assess the PK, safety, and tolerability of SYN-020 delayed release capsules administered orally to healthy adult male and female subjects with a BMI of 18.5 to 27 kg/m2. Up to 36 subjects will participate, in each of up to 6 sequential cohorts. Single doses of 5, 15, 45, and 150 mg SYN-020 are planned in Cohorts 1 through 4, respectively. Cohorts 5 and 6, if enrolled, will receive doses that were well tolerated in an earlier cohort to determine the effect of BMI and/or a high-fat meal on the SYN-020 PK profile. For each cohort, eligible subjects will be admitted to the clinic on Day -1, and receive study drug in the morning of Day 1. For PK analysis, blood and feces will be collected before dosing and for up to 96 hours (blood) or 120 hours (feces) after dosing. Subjects will be discharged from the clinic after the End of Study procedures are completed on Day 6.
Detailed Description
Intestinal alkaline phosphatase (IAP) is a naturally occurring enzyme produced by the small intestine in all mammals, including humans, and is considered essential for promoting normal gastrointestinal (GI) function and maintaining proper gut homeostasis, as well as appearing to play a pivotal role in the mediation of inflammation. SYN-020 is a recombinant bovine IAP isotype II being developed by Synthetic Biologics, Inc. to reduce the cumulative GI toxicity and inflammation that can be associated with repeat administration of radiation in patients with cancer. This is a Phase 1, single-center, open-label, single ascending dose study to assess the PK, safety, and tolerability of SYN-020 delayed release capsules administered orally to healthy adult male and female subjects with a BMI of 18.5 to 27 kg/m2. Up to 36 subjects will participate, with 6 subjects (approximately equal numbers of male and females) in each of up to 6 sequential cohorts. Single doses of 5, 15, 45, and 150 mg SYN-020 are planned in Cohorts 1 through 4, respectively. Cohorts 5 and 6, if enrolled, will receive doses that were well tolerated in an earlier cohort to determine the effect of BMI and/or a high-fat meal on the SYN-020 PK profile, and will be described fully in a protocol amendment. For each cohort, eligible subjects will be admitted to the clinical research unit (CRU) on Day -1, and subjects who remain eligible will, after a minimum 10-hour overnight fast, receive study drug in the morning of Day 1. For PK analysis, blood and feces will be collected before dosing and for up to 96 hours (blood) or 120 hours (feces) after dosing. Subjects will be discharged from the CRU after the End of Study (EOS) procedures are completed on Day 6.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Enteritis Caused by Radiation (Disorder)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
single ascending dose
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SYN-020, 5 mg
Arm Type
Experimental
Arm Description
6 subjects to receive a single 5 mg dose of SYN-020
Arm Title
SYN-020, 15 mg
Arm Type
Experimental
Arm Description
6 subjects to receive a single 15 mg dose of SYN-020
Arm Title
SYN-020, 45 mg
Arm Type
Experimental
Arm Description
6 subjects to receive a single 45 mg dose of SYN-020
Arm Title
SYN-020, 150 mg
Arm Type
Experimental
Arm Description
6 subjects to receive a single 150 mg dose of SYN-020
Intervention Type
Drug
Intervention Name(s)
SYN-020 delayed release capsule
Other Intervention Name(s)
Intestinal Alkaline Phosphatase
Intervention Description
SYN-020, is an opaque, white, size 3 HPMC capsule for oral administration containing enteric-coated, delayed-release pellets.
Primary Outcome Measure Information:
Title
SYN-020 systemic absorption
Description
Analysis of SYN-020 level present in blood
Time Frame
Daily Day 1 through Day 5
Title
SYN-020 presence in feces
Description
Analysis of SYN-020 level present in feces
Time Frame
Daily Day -1 through Day 6
Secondary Outcome Measure Information:
Title
Percentage of Participants with Changes in Clinical Laboratory Testing
Description
Hematology, clinical chemistry, urinalysis, virus serology, drug screen, alcohol screen, pregnancy test, postmenopausal screen
Time Frame
Day -1, Day 2, Day 6
Title
Number of Participants With Changes in Physical exam
Description
Complete and abbreviated physical examinations will be performed
Time Frame
Day 1 and Day 6
Title
Number of Participants with Changes in Vital Signs
Description
Blood pressure, pulse rate, respiratory rate, oral temperature
Time Frame
Daily Day -1 through Day 6
Title
Number of Participants with Changes in Electrocardiograms
Description
12-lead ECG, P-wave, QRS-complex, QT-interval
Time Frame
Day -1, Day 1, Day 2, Day 6
Title
Immunogenicity testing
Description
Measurement of anti-drug antibodies by ELISA
Time Frame
Day 1, Day 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subject is able to read, write, and comprehend English at a sufficient level to understand study related materials, has provided written informed consent before any study-related procedure was performed, and is willing and able to comply with all testing and study requirements. Subject is a healthy male or female, aged 18 through 50 years, inclusive. Subject does not use any tobacco or nicotine product (eg, cigarette, pipe, e-cigarette, vape) and has not used any tobacco or nicotine product for at least 2 months before Day -1. Subject has a BMI of 18.5 to 27 kg/m2 for initial cohorts or, for exploratory cohorts, ≥ 27.1 kg/m2. For Cohorts 1 through 4, if insufficient subjects are available to meet this criterion, subjects with a BMI up to 29 kg/m2 may be included with written authorization from the Sponsor. Subject is healthy based on physical examination, clinical laboratory tests, 12-lead ECG, and vital signs. Subject is willing to minimize the risk of inducing pregnancy from the time of signing the informed consent form (ICF) to at least either 90 days (males) or 30 days (females) after the study drug dose. If female, subject has a negative serum pregnancy test at Screening and on Day -1 (CRU admission). Subject usually has at least 1 bowel movement a day based on self-reporting. Exclusion Criteria: Subject has a history or the presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, vascular, metabolic, collagen, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results. Subject has any known malabsorption syndrome or history of gastrointestinal surgery that could compromise the study objectives. Subject has used any medication (prescription or non-prescription) or herbal supplement, other than prescription hormone replacement therapy (eg, thyroid, testosterone, estrogen) or contraception methods described in Inclusion Criterion #6, within 21 days before Day -1. Subject is pregnant, breastfeeding, or not using a medically accepted method of contraception. Subject is unable to abstain from artificial sweeteners (eg, aspartame, acesulfame potassium, advantame, saccharin, stevia, and sucralose) from CRU admission to the end of study participation. Subject has a positive urine drug or alcohol test at Screening or CRU admission OR has a history of drug/alcohol abuse within 12 months before Screening. Subject has donated more than 500 mL blood during the 3-month period before Day -1. Subject has known intolerance of study drug/ingredients. In the judgment of the Investigator, subject has any factor (eg, other treatment) that could invalidate the study result. Subject is currently enrolled in another clinical study or has received an investigational drug or device within 30 days or within a time period consistent with a washout period of 5 half-lives before signing the ICF, whichever is longer. Subject has already participated in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Sanabria, MD
Organizational Affiliation
Spaulding Clinical Research LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Spaulding Clinical Research LLC
City
West Bend
State/Province
Wisconsin
ZIP/Postal Code
53095
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Pharmacokinetics, Safety, and Tolerability of SYN-020

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