Study of Pharmacokinetics and Safety of Apraglutide in Participants With Normal and Impaired Kidney Function.

NCT ID: NCT04699032

Last Updated: 2024-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-08
• Study Completion Date: 2021-07-05

Brief Summary

Study of pharmacokinetics and safety of apraglutide in participants with normal and impaired kidney function.

Detailed Description

A two stage design, open label, multi-center, non-randomized trial to evaluate the PK and safety of a single subcutaneous dose of 5 mg apraglutide in subjects with varying degrees of renal function. The renal function was calculated by the estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation.

Part 1: 8 subjects with severe renal impairment (Cohort 1) and 8 subjects with normal renal function (Cohort 2).

Part 2: 8 subjects with moderate (Cohort 3) and 8 subjects with mild (Cohort 4). Enrollment into Part 2 was conditional on the results of Part 1.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Severe Renal Impairment

eGFR (mL/min/1.73 m2): \<30 not on hemodialysis

Group Type: EXPERIMENTAL

Apraglutide

Intervention Type: DRUG

Single dose of apraglutide 5 mg.

Normal Healthy Match

eGFR (mL/min/1.73 m2): ≥90

Group Type: EXPERIMENTAL

Apraglutide

Intervention Type: DRUG

Single dose of apraglutide 5 mg.

Moderate Renal Impairment

eGFR (mL/min/1.73 m2): ≥30 to 60

Group Type: EXPERIMENTAL

Apraglutide

Intervention Type: DRUG

Single dose of apraglutide 5 mg.

Mild Renal Impairment

eGFR (mL/min/1.73 m2): ≥60 to 90

Group Type: EXPERIMENTAL

Apraglutide

Intervention Type: DRUG

Single dose of apraglutide 5 mg.

Interventions

Apraglutide

Single dose of apraglutide 5 mg.

Intervention Type: DRUG

Eligibility Criteria

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 ≥17.5 to ≤40 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.

Healthy participants

• No clinically relevant abnormalities (medical history, vital signs, ECG, safety labs)
• eGFR measured by CKD-EPI ≥90 mL/min/1.73 m2) at two screening visits
• Demographically comparable to the group of subjects with impaired renal function:

Participants with impaired renal function

• Severe renal impairment: eGFR <30 mL/min/1.73 m2, but not requiring hemodialysis
• Moderate renal impairment: eGFR ≥30 mL/min/1.73 m2 and <60 mL/min/1.73 m2
• Mild renal impairment: eGFR ≥60 and <90 mL/min/1.73 m2

Exclusion Criteria

All Subjects

• Renal transplant recipients
• History of systemic infection
• Any active malignancies or history of malignancies within the past 2 years
• Acute or chronic medical or psychiatric condition
• Treatment with an IMP within 30 days or 5 half-lives (whichever is longer) preceding the dose of IMP
• Male subjects partners of WOCBP who are unable to comply with the contraceptive measures
• History of clinically significant intestinal adhesions and/or chronic abdominal pain
• History of known colon polyps or family history of familial adenomatous polyposis
• Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or human immunodeficiency virus (HIV)-1 and -2 antibodies
• Serum albumin concentration <25 g/L (2.5 g/dL)
• Hemoglobin concentration <90 g/L (9.0 g/dL)
• Aspartate amino transaminase (AST) or alanine amino transaminase (ALT) values >2 × upper limit of normal (ULN)
• Proteinuria of >3 g total bilirubin >1.5 × ULN
• Positive urine test for alcohol or illicit drugs at either Screening or admission.
• Clinically significant abnormalities on 12-lead ECG
• Use of prescription or non-prescription drugs and dietary supplements within 7 days or five half-lives (whichever is longer) prior to Day 1. Stable concomitant medications may be given to subjects with renal impairment, if they are considered necessary for the welfare of the subjects.
• History of regular alcohol consumption exceeding seven drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces [150 mL] of wine, or 12 ounces [360 mL] of beer, or 1.5 ounces [45 mL] of hard liquor) within 3 months of Screening
• Female subjects of childbearing potential who are unwilling or unable to use highly effective methods of contraception for the duration of the trial and for at least 1 month after the administration of the IMP; pregnant female subjects; female subjects planning to become pregnant during the duration of the trial and until 1 month after the administration of the IMP; breastfeeding female subjects
• Blood donation of approximately 500 mL or more within 60 days prior to the dose of IMP. Plasma donations of approximately 500 mL or more within 28 days prior to the dose of IMP

• Evidence or history of clinically significant abnormalities
• Evidence or history of clinically significant dermatological condition

• Subjects requiring hemodialysis and/or peritoneal dialysis
• Subjects with other clinically significant disease
• Subjects with any significant hepatic, cardiac, or pulmonary disease or subjects who are clinically nephrotic. Hypertension, diabetes mellitus, hyperparathyroidism, ischemic heart disease are not cause for exclusion as long as the subject is medically stable and any drugs that are administered for these conditions are not expected to interfere with the PK of apraglutide.
• Screening BP ≥180 mmHg (systolic) or ≥110 mmHg (diastolic)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

VectivBio AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tomasz Masior

Role: STUDY_DIRECTOR

VectivBio AG

Locations

Orlando Clinical Research Center

Orlando, Florida, United States

Prism Clinical Research, Inc.

Saint Paul, Minnesota, United States

Countries

United States

References

Greig G, Youssef NN, Bolognani F. Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long-Acting, Synthetic glucagon-like peptide-2 Analog With a Unique Pharmacologic Profile, in Individuals With Impaired Renal Function. J Clin Pharmacol. 2024 Jun;64(6):744-754. doi: 10.1002/jcph.2423. Epub 2024 Mar 11.

Reference Type: DERIVED

PMID: 38465515 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TA799-014

Identifier Type: -

Identifier Source: org_study_id