A Phase 1, Open-Label Evaluation of the Pharmacokinetics and Safety of a Single Dose of Apraglutide in Subjects With Normal and Impaired Hepatic Function

The primary objective is to assess the PK of apraglutide in subjects with hepatic impairment compared with matched control subjects with normal hepatic function following single SC dose administration.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Apraglutide

Detailed Description

A two stage design, open label, multi-center, non-randomized trial to evaluate the the safety and tolerability of a single subcutaneous dose of 5 mg apraglutide in subjects with varying degrees of hepatic function. The hepatic function will estimated with the Child-Pugh classification.

Part 1: 8 subjects with moderate hepatic impairment (Cohort 1) and 8 subjects with normal hepatic function (Cohort 2).

Part 2: 8 subjects with mild hepatic impairment (Cohort 3) and 8 subjects with normal hepatic function (from Cohort 2 where possible and additional subject). Part 2 will be conducted only if the geometric mean ratio (GMR) of AUCinf or AUClast for the moderate hepatic impairment group compared to the control group is ≥2.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Münich, Germany
    • APEX
• Slovakia
  • Bratislava, Slovakia
    • Summit Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All Participants:

• Age between 18 and 75 years inclusive
• Subjects who are willing and able to comply with the study procedures
• Subjects able to understand and willing to sign the informed consent
• Body mass index (BMI) of ≥18 to ≤35 kg/m2; and a total body weight of >50 kg (110 lb).
• Women of childbearing potential (WOCBP) on highly effective method of contraception during the trial and for 1 month after the end of trial (EOT) visit. Sterilized or infertile or postmenopausal females.
• Male subjects with a female partner of childbearing potential: highly effective methods of contraception and no sperm donation during the trial and for 1 month after (EOT) visit.

Participants with impaired hepatic function:

• Confirmed and documented diagnosis of cirrhosis
• Moderate liver disease (Child-Pugh B): clinically stable for at least 1 month prior to screening
• Mild liver disease (Child-Pugh A): clinically stable for at least 1 month prior to screening

Exclusion Criteria:

• History of clinically significant GI, bronchopulmonary, neurological, cardiovascular, endocrine, or allergic disease
• Known hypersensitivity to the investigational medicinal product (IMP), any of their excipients or drugs of the same class
• If capable of reproduction, unwilling to use an effective form of contraception
• If a female of child-bearing potential, a positive urine/blood pregnancy test
• Breast-feeding women
• Positive urine/blood test for alcohol and drugs of abuse at Screening and on Day-1
• Use of prohibited medications or herbal remedies
• Known presence or history of intestinal polyps
• Known presence or history of any type of cancer
• Pancreatic events such as acute pancreatitis, pancreatic duct stenosis, pancreas infection, and increased blood amylase and lipase (>2.0-5.0×upper limit of normal range)
• Participation in an investigational drug or device study within 30 days prior to Screening
• Donation of blood over 500 mL within 2 months prior to Screening
• Heavy use of tobacco products (i.e., smokes more than 10 cigarettes per day)
• Concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial
• Any intercurrent clinically significant illness in the previous 28 days before Day 1 of this study
• Positive blood screen for human immunodeficiency virus (HIV) antigen/antibody combo, hepatitis A (HAV), hepatitis B surface antigen (HBsAgB), or hepatitis C virus (HCV)
• Unwillingness or inability to comply with the study protocol for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal hepatic function	Drug: Apraglutide; Single dose of apraglutide 5mg.
Experimental: Moderate hepatic impairment; Child-Pugh B	Drug: Apraglutide; Single dose of apraglutide 5mg.
Experimental: Mild hepatic impairment; Child-Pugh A	Drug: Apraglutide; Single dose of apraglutide 5mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma apraglutide primary PK parameter: AUCinf or AUClast	Area under the curve to infinity (AUCinf) or area under the curve from time zero to the last quantifiable concentration (AUClast) if AUCinf cannot be reliably estimated	0 to 312 hours
Plasma apraglutide primary PK parameter: AUC0-168h	Area under the curve from time zero to 168 hours after apraglutide administration (AUC0-168h)	0 to 168 hours
Maximum observed plasma concentration (Cmax)		0 to 168 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of maximum plasma concentration (tmax)	0 to 168 hours
Apparent clearance after extravascular administration (CL/F)	0 to 168 hours
Apparent volume of distribution after extravascular administration (Vz/F)	0 to 168 hours
Terminal elimination rate constant (λz)	0 to 168 hours
Terminal half-life (t½)	0 to 168 hours
Incidence, nature,and severity of adverse events (AE) with apraglutide	Baseline to Day 16

Collaborators and Investigators

• Sponsor: VectivBio AG
• Investigators: Study Director: Bolognani, VectivBio AG

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Actual): April 4, 2023
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: January 20, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Hepatic Impairment; Liver Function; Hepatic Function
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: TA799-015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No