Assess the Safety, Tolerability and Pharmacokinetics of AZD5055 Following Single and Multiple Ascending Doses in Healthy Participants

NCT05134727 | Completed Phase 1 FDA Drug

• 1 other identifier: D8960C00001
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, First-in-Human study in healthy participants, performed at a single study center, consisting of 2 parts: Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

AZD5055; Single ascending dose; Multiple ascending dose; Porcupine (PORCN) inhibitor; Healthy participants; Oral suspension

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of participants with adverse events (AEs)

  To investigate the safety and tolerability of AZD5055 by assessment of AEs (non-serious and serious) following administration of SAD

  Until Follow-up (7 days post dose) (approximately up to 53 days)

• Part 2: Number of participants with AEs

  To investigate the safety and tolerability of AZD5055 by assessment of AEs (non-serious and serious) following administration of MAD

  Until follow-up (45 days post-last dose) (approximately up to 89 days)

Secondary Outcomes (31)

• Part 1: Maximum observed plasma (peak) drug concentration (Cmax)

  Day 1: profile 0-72 hours after dose

• Part 2: Maximum observed plasma (peak) drug concentration (Cmax)

  Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose

• Part 1: Area under plasma concentration time curve from zero to infinity (AUCinf)

  Day 1: profile 0-72 hours after dose

• Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)

  Day 1: profile 0-48 hours after dose

• Part 1: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)

  Day 1: profile 0-72 hours after dose

Study Arms (2)

Part 1 (single ascending doses [SAD])

EXPERIMENTAL

Healthy participants will be randomized to a single dose of AZD5055 or placebo.

Drug: AZD5055; Drug: Placebo

Part 2 (multiple ascending doses [MAD])

EXPERIMENTAL

Healthy participants will be randomized to repeated dosing with AZD5055 or placebo

Drug: AZD5055; Drug: Placebo

Interventions

AZD5055 DRUG

Healthy participants will receive AZD5055

Part 1 (single ascending doses [SAD]); Part 2 (multiple ascending doses [MAD])

Placebo DRUG

Healthy participants will receive placebo

Part 1 (single ascending doses [SAD]); Part 2 (multiple ascending doses [MAD])

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female (of non-childbearing potential) subjects aged Part 1 (SAD): 18 - 55 years; Part 2 (MAD): 18 - 55 for male and 18 -49 for females, inclusive, with suitable veins for cannulation or repeated venipuncture.
• Female subjects must have a negative pregnancy test.
• Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.
• Male subjects and their women of childbearing potential partners must be willing to use highly effective contraception measures and must refrain from donating sperm or fathering a child from the first day of dosing until 17 days after the last dose of Investigational medicinal product.

You may not qualify if:

• History of any clinically important disease or disorder, or a major medical/surgical procedure or significant trauma within 4 weeks of the first dose of IMP.
• Untreated tuberculosis (TB) or a positive result for the interferon gamma release assay (ie, QuantiFERON TB Gold).
• A positive result for serum hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody, at the Screening Visit.
• Ongoing acquired or inherited immunodeficiency disorders, including but not limited to HIV or common variable immunodeficiency, or the subject is taking immune replacement therapy.
• Individuals with chronic infections (eg, urinary tract infection) or who are at increased risk of infection (eg, surgery, trauma, severe dental disease, or significant infection) within 30 days of screening.
• History of severe COVID-19 infection requiring hospitalization within the last 12 months prior to Screening, or clinical history compatible with Long COVID 19 (symptoms beyond 12 weeks of acute infection).
• History of cancer within the last 10 years (20 years for breast cancer) except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. Any history of lymphoma is not allowed.
• History of osteoporosis, osteomalacia, Paget's disease of the bone, thyrotoxicosis, rheumatoid arthritis, Cushing's disease, or a pathological fracture.
• History of a traumatic fracture within 6 months of the Screening visit.
• A Bone density scans (DEXA scan) bone mineral density value with T-score \< -1 for post-menopausal women and Z score \< -1.5 for male participants and premenopausal women of non-childbearing potential subjects (MAD cohorts only).
• Has received live or live attenuated vaccine in the 30 days prior to dosing, the first dose of COVID-19 vaccine within 30 days prior to randomization, or a COVID 19 vaccine second or booster vaccination within 10 days of screening.
• Ongoing acute gastrointestinal (GI) disease, a history of chronic GI disease, ongoing acute hepatic disease, or a history of chronic hepatic disease, chronic renal disease, pancreatic disease, diabetes mellitus, or any condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• History of Gilbert's syndrome.
• History of muscle disease or rhabdomyolysis.
• Any laboratory values with the deviations at the Screening Visit and/or Day -1 from the reference range.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Focal Dermal Hypoplasia

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Ectodermal Dysplasia; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

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

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 26, 2021
• Study Start: November 18, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in a sponsor approved tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)