SAD, MAD and Food Effect Evaluation of Safety, Tolerability, and PK of AQ280 in Healthy Subjects

A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose, and Food Effect Evaluation Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of AQ280 in Healthy Subjects

The principal aim of this study is to obtain safety and tolerability data when AQ280 is administered orally as single and multiple doses to healthy subjects. This information, together with the pharmacokinetic (PK) data, will help establish the doses and dosing regimen suitable for future studies in patients.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis (EoE)
• Intervention / Treatment: Drug: AQ280; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Fortrea Clinical Research Unit Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Subjects must satisfy all of the following criteria at the screening visit (and/or at check-in, where noted):

1. Males or females, of any race, between 18 and 65 years of age, inclusive.
2. Body mass index between 18.0 and 32.0 kg/m2, inclusive.
3. In good health, determined by no clinically significant findings from medical history, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and check-in and from the physical examination at check-in, as assessed by the investigator (or designee).
4. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
5. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.

Exclusion Criteria:

Subjects will be excluded from the study if they satisfy any of the following criteria at the screening visit (or at check-in, where noted):

Medical conditions

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator (or designee).
3. History of any surgical (eg, stomach or intestinal surgery or resection) or medical condition that would potentially alter absorption, distribution, metabolism, and/or excretion of orally administered drugs. Uncomplicated appendectomy and hernia repair will be allowed. Cholecystectomy will not be allowed.
4. History of any significant infectious disease, as assessed by the investigator, within 2 weeks prior to the first dose of IMP.
5. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) values >1.2 × upper limit of normal (ULN).
6. Congenital nonhemolytic hyperbilirubinemia (including suspicion of Gilbert's syndrome).
7. Hemoglobin value, neutrophil count, and/or lymphocyte count <lower limit of normal.
8. Clinically significant abnormal ECG at screening or check-in.
9. Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects whose results are compatible with prior immunization may be included at the discretion of the investigator

10. Current active tuberculosis based on Quantiferon™ tuberculosis Gold test.

    Prior/concomitant therapy

11. Administration of a coronavirus disease 2019 vaccine in the past 30 days prior to the first dose of investigational medicinal product (IMP).
12. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to the first dose of IMP, unless deemed acceptable by the investigator (or designee).
13. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to the first dose of IMP, unless deemed acceptable by the investigator (or designee).
14. Use or intend to use slow release medications/products considered to still be active within 14 days prior to check in, unless deemed acceptable by the investigator (or designee).

15. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to check in, unless deemed acceptable by the investigator (or designee).

    Prior/concurrent clinical study experience

16. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.

17. Have previously completed or withdrawn from this study.

    Diet and lifestyle

18. Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
19. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in.
20. History of alcoholism or drug/chemical abuse within 2 years prior to check-in.
21. Smoking >5 cigarettes per day, on average, or use the equivalent tobacco- or nicotine containing products per day.

22. Ingestion of poppy seed , Seville orange , star fruit-, or grapefruit containing foods or beverages within 7 days prior to check-in.

    Other exclusions

23. Receipt of blood products within 2 months prior to check-in.
24. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
25. Poor peripheral venous access.
26. Subjects who, in the opinion of the investigator (or designee), should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (SAD): Group A1; Single dose of AQ280, 3 mg or placebo	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part A (SAD): Group A2; Single dose of AQ280, dose to be determined (TBD) or placebo	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part A (SAD): Group A3; Single dose of AQ280, dose TBD or placebo	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part A (SAD): Group A4; Single dose of AQ280, dose TBD or placebo	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part A (SAD): Group A5; Single dose of AQ280, dose TBD or placebo	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part B (MAD): Group B1; AQ280 dose TBD or placebo, once daily (QD) for seven days	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part B (MAD): Group B2; AQ280 dose TBD or placebo, once daily (QD) for seven days	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Experimental: Part B (MAD): Group B3; AQ280 dose TBD or placebo, once daily (QD) for seven days	Drug: AQ280; Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral; Drug: Placebo; Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (SAD): Number of treatment emergent adverse events (TEAEs) per subject		Part A (SAD): Screening up to Day 8(±2)
Part A (SAD): Number of subjects with clinically significant abnormalities in vital signs	Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature	Part A (SAD): Screening up to Day 3
Part A (SAD): Number of subjects with abnormal ECG	QTcF interval of >450 msec for males and >470 msec for females, or change from baseline of >30 msec	Part A (SAD): Screening up to Day 3
Part A (SAD): Number of subjects with clinically significant changes in laboratory evaluations		Part A (SAD): Screening up to Day 3
Part A (Food Effect): Number of treatment emergent adverse events (TEAEs) per subject		Part A (Food Effect): Screening up to Day 18(±2)
Part A (Food Effect): Number of subjects with clinically significant abnormalities in vital signs	Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature	Part A (Food Effect): Screening up to Day 13
Part A (Food Effect): Number of subjects with abnormal ECG	QTcF interval of >450 msec for males and >470 msec for females, or change from baseline of >30 msec	Part A (Food Effect): Screening up to Day 13
Part A (Food Effect): Number of subjects with clinically significant changes in laboratory evaluations		Part A (Food Effect): Screening up to Day 13
Part B (MAD): Number of treatment emergent adverse events (TEAEs) per subject		Part B (MAD): Screening up to Day 14(±3)
Part B (MAD): Number of subjects with clinically significant abnormalities in vital signs	Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature	Part B (MAD): Screening up to Day 14(±3)
Part B (MAD): Number of subjects with abnormal ECG	QTcF interval of >450 msec for males and >470 msec for females, or change from baseline of >30 msec	Part B (MAD): Screening up to Day 14(±3)
Part B (MAD): Number of subjects with clinically significant changes in laboratory evaluations		Part B (MAD): Screening up to Day 14(±3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (SAD) - Primary PK parameters derived from plasma concentration-time profile of AQ280: area under the concentration time curve from time 0 extrapolated to infinity	Area under the concentration time curve over a dosing interval (AUCτ) may be included as a primary PK parameter if AUC 0-infinity cannot be calculated	Days 1, 2 and 3
Part A (SAD) - Primary PK parameter derived from plasma concentration-time profile of AQ280: maximum observed concentration (Cmax)		Days 1, 2 and 3
Part A (SAD) - Primary PK parameter derived from plasma concentration-time profile of the AQ280 main metabolite, AQ282: area under the concentration time curve from time 0 extrapolated to infinity	Area under the concentration time curve over a dosing interval (AUCτ) may be included as a primary PK parameter if AUC 0-infinity cannot be calculated	Days 1, 2 and 3
Part A (SAD) - Primary PK parameter derived from plasma concentration-time profile of the AQ280 main metabolite, AQ282: maximum observed concentration (Cmax)		Days 1, 2 and 3
Part A (SAD) - Difference in Primary PK parameters derived from plasma concentration-time profile of AQ280: area under the concentration time curve from time 0 extrapolated to infinity in fasted state and in fed state	Area under the concentration time curve over a dosing interval (AUCτ) may be included as a primary PK parameter if AUC 0-infinity cannot be calculated	Days 1, 2 and 3
Part A (SAD) - Difference in Primary PK parameters derived from plasma concentration-time profile of AQ280: maximum observed concentration (Cmax) in fasted state and in fed state	Area under the concentration time curve over a dosing interval (AUCτ) may be included as a primary PK parameter if AUC 0-infinity cannot be calculated	Days 1, 2 and 3
Part B (MAD) - Primary PK parameters derived from plasma concentration-time profile of AQ280: accumulation ratio (AR)		Day 1 and Day 7
Part B (MAD) - Primary PK parameters derived from plasma concentration-time profile of AQ280: area under the concentration time curve over a dosing interval (AUCτ)		Day 1 and Day 7
Part B (MAD) - Primary PK parameters derived from plasma concentration-time profile of AQ280: maximum observed concentration (Cmax)		Day 1 and Day 7
Part B (MAD) - Primary PK parameter derived from plasma concentration-time profile of the AQ280 main metabolite, AQ282: area under the concentration time curve over a dosing interval (AUCτ)		Day 1 and Day 7
Part B (MAD) - Primary PK parameter derived from plasma concentration-time profile of the AQ280 main metabolite, AQ282: maximum observed concentration (Cmax)		Day 1 and Day 7

Collaborators and Investigators

• Sponsor: AQILION AB
• Investigators: Study Director: Jan Törnell, MD, PhD, AQILION AB

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2022
• Primary Completion (Actual): July 10, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis
• Other Study ID Numbers: ARIA-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No