Trial Outcomes & Findings for Study of Pharmacokinetics and Safety of Apraglutide in Participants With Normal and Impaired Kidney Function. (NCT NCT04699032)

Last Updated: 2024-10-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

5 minutes pre-dose up to 240 hours after dosing on Day 1

Results posted on

2024-10-26

Participant Flow

This study was performed in the United States of America between 08 December 2020 and 05 July 2021.

16 participants were included in Part 1 of the study and received 5 mg subcutaneous (SC) apraglutide on Day 1. Of the 16 participants who were included in Part 1, eight had normal renal function and eight had severely impaired renal function. Enrollment into Part 2 of the study was conditional on the results of Part 1. No participants were enrolled into Part 2.

Participant milestones

Participant milestones
Measure	Severely Impaired Renal Function Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function Participants with estimated glomerular filtration rate (eGFR) values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Severely Impaired Renal Function n=8 Participants Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function n=8 Participants Participants with eGFR values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.	Total n=16 Participants Total of all reporting groups
Age, Continuous	66 years n=5 Participants	60 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	90.1 kg n=5 Participants	86.7 kg n=7 Participants	88.4 kg n=5 Participants
Height	171.9 cm n=5 Participants	174.9 cm n=7 Participants	173.4 cm n=5 Participants
Body mass index	30.6 kg/m^2 n=5 Participants	28.3 kg/m^2 n=7 Participants	29.4 kg/m^2 n=5 Participants
Estimated glomerular filtration rate	21.3 mL/min/1.73m^2 n=5 Participants	96.3 mL/min/1.73m^2 n=7 Participants	58.8 mL/min/1.73m^2 n=5 Participants

PRIMARY outcome

Timeframe: 5 minutes pre-dose up to 240 hours after dosing on Day 1

Population: The PK parameter analysis population included all participants assigned to the investigational medicinal product (IMP) who were treated and had at least one of the PK parameters of primary interest measured.

Outcome measures

Outcome measures
Measure	Severely Impaired Renal Function n=8 Participants Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function n=8 Participants Participants with eGFR values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.
Maximum Plasma Concentration (Cmax) of Apraglutide	39.5 ng/mL Standard Deviation 13.7	65.8 ng/mL Standard Deviation 37.5

PRIMARY outcome

Timeframe: 5 minutes pre-dose up to 240 hours after dosing on Day 1

Population: The PK parameter analysis population included all participants assigned to the IMP who were treated and had at least one of the PK parameters of primary interest measured.

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.

Outcome measures

Outcome measures
Measure	Severely Impaired Renal Function n=8 Participants Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function n=8 Participants Participants with eGFR values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Apraglutide	3330 h*ng/mL Standard Deviation 1150	5050 h*ng/mL Standard Deviation 3170

SECONDARY outcome

Timeframe: Day 1 up to Day 14

Population: The Safety Set included all participants who received at least one dose of the IMP.

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.

Outcome measures

Outcome measures
Measure	Severely Impaired Renal Function n=8 Participants Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function n=8 Participants Participants with eGFR values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 1 up to Day 14

Population: The Safety Set included all participants who received at least one dose of the IMP.

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

Outcome measures

Outcome measures
Measure	Severely Impaired Renal Function n=8 Participants Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function n=8 Participants Participants with eGFR values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.
Number of TEAEs Any Mild TEAEs	4 events	1 events
Number of TEAEs Any Moderate TEAEs	3 events	2 events
Number of TEAEs Any Severe TEAEs	0 events	0 events
Number of TEAEs Any Serious TEAEs	0 events	0 events
Number of TEAEs Any TEAEs	7 events	3 events
Number of TEAEs Any Treatment-Related TEAEs	5 events	0 events
Number of TEAEs Any TEAEs leading to study discontinuation	0 events	0 events

Adverse Events

Severely Impaired Renal Function

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Normal Renal Function

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Severely Impaired Renal Function n=8 participants at risk Participants with eGFR values \<30 mL/min/1.73 m\^2, but not requiring hemodialysis, received 5 mg SC apraglutide on Day 1.	Normal Renal Function n=8 participants at risk Participants with eGFR values ≥90 mL/min/1.73 m\^2 received 5 mg SC apraglutide on Day 1.
General disorders Chest pain	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
General disorders Injection site hemorrhage	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
General disorders Injection site papule	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Investigations Alanine aminotransferase increased	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Investigations Blood creatinine increased	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Nervous system disorders Headache	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/8 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.	12.5% 1/8 • Number of events 1 • Day 1 up to Day 14 The Safety Set included all participants who received at least one dose of the IMP.

Additional Information

Reda Sheik

VectivBio AG

Phone: +41615513030

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place