A First-in-human Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of APC148 in Healthy Adults

NCT06360640 | Completed Phase 1

• 2 other identifiers: APC148-0012023-507939-38-00
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this first-in-human trial is to investigate the safety, tolerability, and pharmacokinetics of APC148 after intravenous (IV) infusion of single ascending doses in healthy adults.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (14)

• Incidence and intensity of adverse events (AEs)

  Frequency, intensity and seriousness of adverse events (AEs) will be assessed. The intensity grades is defined as mild, moderate or severe. AEs will be assessed as not related, possibly or probably related to the investigational medicinal product (IMP)

  From start of infusion until end of trial visit Day 8

• Incidence and intensity of serious adverse events (SAEs)

  Frequency, intensity and seriousness of Serious adverse events (SAEs) will be assessed. Assessment of causal relationship to IMP will be assessed.

  From start of infusion until end of trial visit Day 8

• Incidence and intensity of infusion-related AEs

  Frequency, intensity and seriousness of infusion-related adverse events (AEs) will be assessed. The intensity grades is defined as mild, moderate or severe. AEs will be assessed as not related, possibly or probably related to the investigational medicinal product (IMP)

  From start of infusion until end of trial visit Day 8

• Time course of local tolerability reactions

  The infusion site area will be visually inspected before, during and after the IMP infusion. The assessment will include the Investigator's evaluation of swelling, haematoma, and erythema. In addition, each participant will assess their subjective experience of pain and pruritus. Local tolerability reactions will be recorded as infusion-related Adverse events (AEs)

  Pre-dose, Day 1, Day 2 and Day 8

• Changes from baseline in blood pressure

  Systolic and diastolic blood pressure and pulse will be measured in supine position after 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in respiratory rate

  Respiratory rate will be measured in supine position after 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in body temperature

  Body temperature will be measured in supine position after 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day1, Day 2, Day 3 and Day 8

• Changes from baseline in heart rate

  Heart rate will be measured in supine position after 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in PQ/PR interval

  Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. PQ/PR intervals will be recorded. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in QRS interval

  Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. QRS intervals will be recorded. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in QT interval

  Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. QT intervals will be recorded. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in QTcF interval

  Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. QTcF intervals will be recorded. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in Clinical Laboratory Profile

  Safety laboratory data, Clinical chemistry, haematology, and coagulation, will be measured. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator.

  Day -1, Day 1, Day 2, Day 3 and Day 8

• Changes from baseline in physical examination

  Assessment of different organ systems. Clinically significant and non-clinically significant abnormal findings will be summarised by treatment and dose.

  Day -1, Day 1, Day 3 and Day 8

Secondary Outcomes (14)

• APC148 plasma concentrations

  Day 1, Day 2 and Day 3

• APC148 urine concentrations

  Day 1 and Day 2

• Pharmacokinetic (PK) parameter in plasma - Area under curve (AUC) 0-24

  Day 1, Day 2, Day 3

• PK parameter in plasma - AUC0-inf

  Day 1, Day 2, Day 3

• PK parameter in plasma - AUC0-last

  Day 1, Day 2, Day 3

Study Arms (6)

50 mg of APC148 and placebo

EXPERIMENTAL

Cohort 1: 4 participants receives 3 hours IV administration of 50 mg APC148, and 2 participants placebo.

Drug: APC148 and Placebo

150 mg of APC148 and placebo

EXPERIMENTAL

Cohort 2: 6 participants receives 3 hours IV administration of 150 mg APC148 and 2 participants placebo.

Drug: APC148 and Placebo

300 mg of APC148 and placebo

EXPERIMENTAL

Cohort 3: 6 participants receives 3 hours IV administration of 300 mg APC148 and 2 participants placebo.

Drug: APC148 and Placebo

450 mg of APC148 and placebo

EXPERIMENTAL

Cohort 4: 6 participants receives 3 hours IV administration of 450 mg APC148 and 2 participants placebo.

Drug: APC148 and Placebo

600 mg of APC148 and placebo

EXPERIMENTAL

Cohort 5: 6 participants receives 3 hours IV administration of 600 mg APC148 and 2 participants placebo.

Drug: APC148 and Placebo

900 mg of APC148 and placebo

EXPERIMENTAL

Cohort 6: 6 participants receives 3 hours IV administration of 900 mg APC148 and 2 participants placebo.

Drug: APC148 and Placebo

Interventions

APC148 and Placebo DRUG

IV infusion

150 mg of APC148 and placebo; 300 mg of APC148 and placebo; 450 mg of APC148 and placebo; 50 mg of APC148 and placebo; 600 mg of APC148 and placebo; 900 mg of APC148 and placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give written informed consent for participation in the trial.
• Healthy females of non-childbearing potential and healthy males aged ≥18 and ≤60 years at the time of the screening visit.
• BMI ≥ 18.5 and ≤ 30.0 at the time of the screening visit, and body weight of ≥50 and ≤100 kg.
• Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of the screening visit, as judged by the Investigator.
• Male participants must be willing to use condom or be vasectomised or practice sexual abstinence from heterosexual intercourse and refrain from donating sperm from the administration of investigational medicinal product (IMP) until 3 months after the administration of IMP. Any female partner of a non-vasectomised male participant who is of child-bearing potential must use a highly effective method of contraception with a failure rate of \<1 % to prevent pregnancy from at least 2 weeks prior to the administration of IMP to 3 months after the administration of IMP.
• Women of non-childbearing potential.
• Adequate renal function at the screening visit: Creatinine estimated glomerular filtration rate (eGFR) ≥80 mL/min/1.73 m2 for participants aged 18-50 years and eGFR ≥60 mL/min/1.73 m2 for participants ≥51 years and S-creatinine ≤ upper limit of normal.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant's ability to participate in the trial.
• History of kidney disease or renal stone.
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP.
• Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
• Any planned major surgery within the duration of the trial.
• After 10 minutes supine rest at the screening visit, any vital signs values outside the following ranges:
• Systolic blood pressure: \<90 or ≥140 mmHg, or
• Diastolic blood pressure \<50 or ≥90 mmHg, or
• Pulse \<40 or \>90 bpm
• A mean QTcF (QT corrected for heart rate by Fredericia's formula) interval of \>450 ms after triplicate measurements. The average of the 3 QTc(F) values will be used to determine the participant's eligibility.
• lead ECG:
• with PR interval shortening \< 120 ms.
• PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre- excitation OR
• PR interval prolongation \> 220 ms OR
• Intermittent second or third degree atrioventricular (AV) block, or AV dissociation

Sponsors & Collaborators

• AdjuTec Pharma AS: lead
• CTC Clinical Trial Consultants AB: collaborator

Study Sites (1)

Clinical Trial Consultants AB

Uppsala, Sweden

Location

Study Officials

• Erik Rein-Hedin, MD

  Clinical Trial Consultants AB (CTC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind trial.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-controlled, 6 sequential cohorts.

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: April 11, 2024
• Study Start: September 2, 2024
• Primary Completion: March 10, 2025
• Study Completion: March 10, 2025
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)