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

Healthy Subjects Clinical Trial

Official title:

A First-in-human, Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of APC148 in Healthy Adults

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06360640
• Other study ID #: APC148-001
• Secondary ID: 2023-507939-38-0
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: AdjuTec Pharma AS
• Contact: Caroline Hammarström, MSc
• Phone: 0046 (0) 705292158
• Email: caroline.hammarstrom[@]ctc-ab.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Participants will receive a single 3-hours IV infusion of APC148 or placebo. 6 sequential cohorts are planned. The first 2 subjects in each cohort will be dosed in a sentinel fashion. The subjects will be followed for 7 days.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• 12-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

• History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome.

• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to APC148.

• Regular use of any prescribed or non-prescribed medications, including antacids, analgesics, herbal remedies, vitamins and minerals, within 2 weeks prior to the administration of IMP, except occasional intake of paracetamol (maximum 2000 mg/day and not exceeding 3000 mg/week), as well as nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.

• Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis B/C antibodies and/or HIV.

• Positive result for drugs of abuse or alcohol at the screening visit or on admission to the trial site prior to the administration of the IMP.

• Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Participants consented and screened but not dosed in previous Phase I trials are not to be excluded.

• Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times/week is allowed before the screening visit.

• History of, or current, drug abuse, use of anabolic steroids, alcohol abuse or excessive intake of alcohol, as judged by the Investigator.

• Excessive caffeine consumption defined by a daily intake of > 5 cups (1 cup = approximately 240 mL) of caffeine containing beverages, as judged by the Investigator.

• Plasma donation within 1 month of the IMP infusion or blood donation (or corresponding blood loss) during the last 3 months prior to the IMP infusion.

• Participated in a previous cohort in the trial.

• The Investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• APC148 and Placebo
IV infusion

Locations

Country	Name	City	State
Sweden	Clinical Trial Consultants AB	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
AdjuTec Pharma AS	CTC Clinical Trial Consultants AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	APC148 plasma concentrations	Concentration of APC148 in plasma. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2 and Day 3
Secondary	APC148 urine concentrations	Concentration of APC148 in urine. Urine samples for the determination of plasma concentrations will be collected.	Day 1 and Day 2
Secondary	Pharmacokinetic (PK) parameter in plasma - Area under curve (AUC) 0-24	Area under the plasma concentration vs. time curve from time 0 to 24 hours. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - AUC0-inf	AUC from time 0 to infinity. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - AUC0-last	AUC from time 0 to the last measurable concentration. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - Cmax	Maximum observed plasma concentration. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - Tmax	Time to Cmax. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - T1/2	Terminal elimination half-life. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - Clearance (CL)	Total clearance. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - Vz	Volume of distribution. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameter in plasma - Vss determination of plasma concentrations will be collected.	Apparent volume of distribution at equilibrium. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations will be collected.	Day 1, Day 2, Day 3
Secondary	PK parameters in urine - A(e)	Urine samples for the amount of unchanged drug excreted into urine (Ae) will be collected.	Day 1 and Day 2
Secondary	PK parameters in urine - fe	Urine samples for the Fraction of IV administered drug that is excreted into urine will be collected.	Day 1 and Day 2
Secondary	PK parameter in urine - renal clearance (CLr)	Urine samples for Renal clearance will be collected.	Day 1 and Day 2