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

Phase 1

Completed

Conditions: Chronic Kidney Disease

Interventions: Drug: Apraglutide

Registration Number: NCT04699032

Lead Sponsor: VectivBio AG

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Additional Exclusion Criteria for Healthy Subjects with Normal Renal Function

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

Additional Exclusion Criteria for Subjects with Impaired Renal Function

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moderate Renal Impairment	Apraglutide	eGFR (mL/min/1.73 m2): ≥30 to 60
Severe Renal Impairment	Apraglutide	eGFR (mL/min/1.73 m2): \<30 not on hemodialysis
Normal Healthy Match	Apraglutide	eGFR (mL/min/1.73 m2): ≥90
Mild Renal Impairment	Apraglutide	eGFR (mL/min/1.73 m2): ≥60 to 90

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Apraglutide	5 minutes pre-dose up to 240 hours after dosing on Day 1	PK samples collected for the measurement of plasma concentration of apraglutide were analyzed using a validated analytical method in compliance with applicable standard operating procedures.
Maximum Plasma Concentration (Cmax) of Apraglutide	5 minutes pre-dose up to 240 hours after dosing on Day 1	Pharmacokinetic (PK) samples collected for the measurement of plasma concentration of apraglutide were analyzed using a validated analytical method in compliance with applicable standard operating procedures.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Day 1 up to Day 14	TEAEs were defined as adverse events (AEs) that occurred after dosing the participant with the study drug. Participants with more than one TEAE were counted only once using the most severe event. Vital signs, triplicate 12-lead electrocardiograms, or clinical laboratory assessments considered clinically significant by the Investigator were reported as AEs.
Number of TEAEs	Day 1 up to Day 14	The Investigator used the adjectives mild, moderate, or severe to describe the maximum intensity of the AE. These were defined as follows: * Mild: did not interfere with participant's usual function * Moderate: interfered to some extent with participant's usual function * Severe: interfered significantly with participant's usual function. The Investigator systematically assessed the causal relationship of AEs to IMP/trial treatment using the definitions below: * Not related: Not reasonably related to the IMP. The AE could not medically (pharmacologically/clinically) be attributed to the IMP * Related: Reasonably related to the IMP. The AE could medically (pharmacologically/clinically) be attributed to the IMP. A serious AE (SAE) was classified as any AE that: * Resulted in death * Was life-threatening * Required or prolonged in-patient hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect in a neo

Trial Locations

Locations (2): Prism Clinical Research, Inc.
🇺🇸
Saint Paul, Minnesota, United States
Orlando Clinical Research Center
🇺🇸
Orlando, Florida, United States