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

NCT05485779 | Completed Phase 1 Results

• 1 other identifier: ARIA-1
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Eosinophilic Esophagitis (EoE)

Outcome Measures

Primary Outcomes (10)

• Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant

  The number of participants who experienced a treatment-emergent event (TEAE) are presented.

  Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts

• Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced

  The number of total events experienced by participants are presented.

  Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts

• Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant

  The number of participants who experienced a treatment-emergent event (TEAE) are presented.

  Part B (MAD): Screening up to Day 14(±3)

• Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced

  The number of total TEAE events experienced by participants are presented.

  Part B (MAD): Screening up to Day 14(±3)

• Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs

  The number of participants with clinically significant abnormalities in vital signs is presented. 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 Participants With Abnormal ECG

  The number of participants with abnormal electrocardiogram (ECG) results is presented. Abnormal ECGs were considered to be those with a QTcF interval of greater than 450 msec for males and greater than 470 msec for females, or change from baseline of greater than 30 msec.

  Part A (SAD): Screening up to Day 3

• Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations

  The number of participants with clinically significant changes in any laboratory evaluations (clinical chemistry, haematology, coagulation, or urinalysis) is presented.

  Part A (SAD): Screening up to Day 3

• Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs

  The number of participants with clinically significant abnormalities in vital signs is presented. 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 Participants With Abnormal ECG

  The number of participants with abnormal electrocardiogram (ECG) results is presented. Abnormal ECGs were considered to be those with a QTcF interval of greater than 450 msec for males and greater than 470 msec for females, or change from baseline of greater than 30 msec.

  Part B (MAD): Screening up to Day 14(±3)

• Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations

  The number of participants with clinically significant changes in any laboratory evaluations (clinical chemistry, haematology, coagulation, or urinalysis) is presented.

  Part B (MAD): Screening up to Day 14(±3)

Secondary Outcomes (11)

• 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

  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

  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 Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity in Fasted State and in Fed State

  Days 1, 2 and 3

Study Arms (8)

Part A (SAD): Group A1

EXPERIMENTAL

Single dose of AQ280, 3 mg or placebo

Drug: AQ280; Drug: Placebo

Part A (SAD): Group A2

EXPERIMENTAL

Single dose of AQ280, dose to be determined (TBD) or placebo

Drug: AQ280; Drug: Placebo

Part A (SAD): Group A3

EXPERIMENTAL

Single dose of AQ280, dose TBD or placebo

Drug: AQ280; Drug: Placebo

Part A (SAD): Group A4

EXPERIMENTAL

Single dose of AQ280, dose TBD or placebo

Drug: AQ280; Drug: Placebo

Part A (SAD): Group A5

EXPERIMENTAL

Single dose of AQ280, dose TBD or placebo

Drug: AQ280; Drug: Placebo

Part B (MAD): Group B1

EXPERIMENTAL

AQ280 dose TBD or placebo, once daily (QD) for seven days

Drug: AQ280; Drug: Placebo

Part B (MAD): Group B2

EXPERIMENTAL

AQ280 dose TBD or placebo, once daily (QD) for seven days

Drug: AQ280; Drug: Placebo

Part B (MAD): Group B3

EXPERIMENTAL

AQ280 dose TBD or placebo, once daily (QD) for seven days

Drug: AQ280; Drug: Placebo

Interventions

AQ280 DRUG

Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral

Part A (SAD): Group A1; Part A (SAD): Group A2; Part A (SAD): Group A3; Part A (SAD): Group A4; Part A (SAD): Group A5; Part B (MAD): Group B1; Part B (MAD): Group B2; Part B (MAD): Group B3

Placebo DRUG

Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral

Part A (SAD): Group A1; Part A (SAD): Group A2; Part A (SAD): Group A3; Part A (SAD): Group A4; Part A (SAD): Group A5; Part B (MAD): Group B1; Part B (MAD): Group B2; Part B (MAD): Group B3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy all of the following criteria at the screening visit (and/or at check-in, where noted):
• Males or females, of any race, between 18 and 65 years of age, inclusive.
• Body mass index between 18.0 and 32.0 kg/m2, inclusive.
• 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).
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.

You may not qualify if:

• 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
• 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).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator (or designee).
• 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.
• History of any significant infectious disease, as assessed by the investigator, within 2 weeks prior to the first dose of IMP.
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) values \>1.2 × upper limit of normal (ULN).
• Congenital nonhemolytic hyperbilirubinemia (including suspicion of Gilbert's syndrome).
• Hemoglobin value, neutrophil count, and/or lymphocyte count \<lower limit of normal.
• Clinically significant abnormal ECG at screening or check-in.
• 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
• Current active tuberculosis based on Quantiferon™ tuberculosis Gold test.
• Prior/concomitant therapy
• Administration of a coronavirus disease 2019 vaccine in the past 30 days prior to the first dose of investigational medicinal product (IMP).
• 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).

Sponsors & Collaborators

• AQILION AB: lead

Study Sites (1)

Fortrea Clinical Research Unit Ltd.

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Conditions

Eosinophilic Esophagitis

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Anneli Tinnerholm
• Organization: AQILION AB

anneli.tinnerholm@aqilion.com

+46 730 88 14 15

Study Officials

• Jan Törnell, MD, PhD

  AQILION AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: August 3, 2022
• Study Start: July 20, 2022
• Primary Completion: July 10, 2023
• Study Completion: July 10, 2023
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)