A Phase 1 Randomised, Double-Blind, Placebo-Controlled 3 Part Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7798 Following Single Ascending Dose Administration and Repeat Dose Administration in Healthy Subjects (Including Japanese and Chinese Subjects), and Patients With Crohn's Disease
Overview
- Phase
- Phase 1
- Intervention
- AZD7798
- Conditions
- Healthy Subjects
- Sponsor
- AstraZeneca
- Enrollment
- 112
- Locations
- 1
- Primary Endpoint
- Number of participants with Adverse Events (AEs)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
This study will assess the safety, tolerability, immunogenicity, and pharmacokinetics (PK), and explore the pharmacodynamics (PD) following single ascending dose administration and repeat dose administration in healthy subjects and patients with Crohn's disease.
Detailed Description
This is a Phase I, randomised, double-blind, placebo controlled study in healthy male and female subjects as well as patients with Crohn's disease performed at a single study centre. This study is comprised of 3 parts: Part 1 (sub-parts 1a and 1b), Part 2, and Part 3 (sub-Parts 3a and 3b). * Part 1a: This is a First-In-Human (FIH), single ascending dose (SAD) sequential group study. Up to 7 dose levels of AZD7798 are planned to be investigated. Depending on the findings, an additional dose may be added. Up to 80 healthy subjects are planned to be included. Eight subjects will participate in each single dose cohort. Within each cohort, 6 subjects will be randomised to receive AZD7798, and 2 subjects will be randomised to receive placebo. Each subject will be enrolled up to 113 days (approximately 16 weeks). * Part 1b: Up to 8 subjects will be randomised to receive a planned dose of AZD7798 (up to 6 subjects) or placebo (up to 2 subjects) on Day 1 and Day 15. This cohort is planned to start after completion of the single dose level cohort in Part 1a. Each subject will be enrolled up to 149 days (approximately 21 weeks). * Part 2: Up to 8 patients will be randomised (2:1:1) into 1 of 3 strata and receive: * Stratum 1: AZD7798 on Day 1 and Day 15 (up to 4 patients). * Stratum 2: Placebo on Day 1 and AZD7798 on Day 15 (up to 2 patients). * Stratum 3: AZD7798 on Day 1 and placebo on Day 15 (up to 2 patients). Each subject will be enrolled up to 149 days (approximately 21 weeks). * Part 3: Subjects will be randomised to AZD7798 or placebo in a ratio of 3:1 (up to 6 subjects will receive AZD7798 and up to 2 subjects will receive placebo).
Investigators
Eligibility Criteria
Inclusion Criteria
- •All Study Parts:
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
- •Subjects must have suitable veins for cannulation or repeated venepuncture.
- •Males who are sexually active with a female partner of childbearing potential and who have not had a vasectomy must agree to comply with highly effective methods of contraception from the time of IMP administration until 4 months after the last dose of IMP.
- •Non-smoker, or mild smoker (no more than 10 cigarettes per day).
- •Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 45 kg and no more than 100 kg inclusive.
- •Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating.
- •Provision of signed, written and dated informed consent for optional genetic/biomarker research.
- •Evidence of completion of an appropriate vaccination regimen to SARS-CoV-2 at least 14 days prior to screening as appropriate and recommended in contemporaneous local, regional, or national guidelines.
- •Part 1 (Healthy Subjects), Part 3a (Healthy Japanese Subjects) and Part 3b (Healthy Chinese Subjects):
Exclusion Criteria
- •All Study Parts:
- •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational Medicinal Product (IMP).
- •Any positive result on Screening for HBsAg, anti-HBc antibody, anti-HCV antibody, and HIV.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or, history of hypersensitivity to drugs with a similar chemical structure or class to AZD
- •For females of childbearing potential using hormonal contraception: Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- •Subjects with a positive diagnostic nucleic acid test (using PCR) for SARS-CoV-2 prior to dosing.
- •Live or attenuated vaccine within 4 weeks of Visit 1 and until the end of the follow up period.
- •An active infection, or history of serious infection within the preceding 28 days.
- •Use of antibiotics within 28 days prior to the first administration of IMP.
- •History of symptomatic herpes simplex (excluding cold sores) or herpes zoster infection within 3 months prior to screening.
Arms & Interventions
Part 1a - Cohort 1: AZD7798 dose 1
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1a - Cohort 2: AZD7798 dose 2
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1a - Cohort 3: AZD7798 dose 3
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1a - Cohort 4: AZD7798 dose 4
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1a - Cohort 5: AZD7798 dose 5
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1a - Cohort 6: AZD7798 dose 6
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1a - Cohort 7: AZD7798 dose 7
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 1b - Cohort 8: AZD7798 dose 8
A total of 6 subjects will receive repeat doses of AZD7798.
Intervention: AZD7798
Part 1a - Spare Cohort 9: AZD7798 dose 9
A total of 6 subjects will receive a single ascending dose of AZD7798.
Intervention: AZD7798
Part 2 - Cohort 10: AZD7798 + AZD7798
A total of 4 subjects will receive a single dose on Day 1 followed by a single dose on Day 15.
Intervention: AZD7798
Part 2 - Cohort 11: Placebo + AZD7798
A total of 2 subjects will receive placebo on day 1 followed by AZD7798 on day 15.
Intervention: AZD7798
Part 2 - Cohort 12: AZD7798 + Placebo
A total of 2 subjects will receive AZD7798 on day 1 followed by placebo on day 15.
Intervention: AZD7798
Placebo: Part 1a and Part 1b
A total of 2 subjects per cohort will receive placebo.
Intervention: Placebo
Part 3a - Cohort 12: AZD7798
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Part 3b - Cohort 13: AZD7798
A total of 6 subjects will receive single ascending doses of AZD7798.
Intervention: AZD7798
Placebo: Part 3a and Part 3b
A total of 2 subjects per cohort will receive placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with Adverse Events (AEs)
Time Frame: Until follow-up (Day 85) or Early termination (ET)
The safety and tolerability of AZD7798 following administration of single ascending doses will be assessed.
Secondary Outcomes
- Area under plasma concentration time curve from zero to infinity (AUCinf)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Maximum serum concentration (Cmax)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Apparent total clearance (CL/F)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- AUClast(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Cmax/D(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Percentage of patients with antidrug antibodies (ADAs)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Time to reach maximum serum concentration (tmax)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Time to last measurable concentration (tlast)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Volume of distribution based on the terminal phase (Vz)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Apparent volume of distribution based on terminal phase (Vz/F)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- AUClast/D(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Terminal elimination half-life (t½λz)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Systemic clearance (CL)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Bioavailability (F)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- Volume of distribution at steady state (Vss)(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)
- AUCinf/D(Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85)