A Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of Subcutaneous AZD6912 in Healthy Participants

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase I, Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Study of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of Subcutaneous AZD6912 in Healthy Participants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06115967
• Other study ID #: D7130C00001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 15, 2023
• Est. completion date: July 8, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of AZD6912 administered subcutaneously (SC) in healthy participants.

Description:

In this First-In-Human (FiH) study, eligible participants will be randomly assigned to 6 cohorts in a 3:1 ratio to receive either a single dose of AZD6912 SC or placebo. The first 2 participants in each cohort will be dosed as a sentinel pair, with one receiving AZD6912 SC and the other receiving placebo.

The study will comprise of, a screening period of 70 days, a treatment period where participants will stay at the Clinical Unit from the day before study intervention administration until at least 240 hours and will be discharged on Day 11. Outpatient visits would start weekly from Day 15, then bi-weekly from Day 43, 4-weekly from Day 99, and 6-weekly from Day 155, with additional follow-up visits as needed.

The study will last approximately 22 months, with each participant participating for about 38 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: July 8, 2025
• Est. primary completion date: July 8, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Females must have a negative pregnancy test.

• Contraceptive use by males and females should be consistent with local regulations.

• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.

• For optional Japanese participants only:

• Participants must be of Japanese descent defined as: first generation (born to 2 Japanese parents and 4 Japanese grandparents).

• Born in Japan, and not have lived outside Japan for more than 5 years.

• Lifestyle, including diet, must not have significantly changed since leaving Japan.

Exclusion Criteria:

• History of any clinically important disease or disorder.

• Current or recurrent disease of clinical significance that could affect clinical assessments or clinical laboratory evaluations.

• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.

• History of congenital or acquired immunodeficiency or complement deficiency or an underlying condition that predisposes to infection.

• History of any Neisseria infection, unexplained, recurrent infections, or infection requiring treatment with systemic antibiotics.

• Evidence of hepatitis B infection (positive for HBsAg or positive for anti-HBcAb) or hepatitis C viral infection (HCV Abs or hepatitis C RNA positive) or HIV infection (positive for HIV type 1 or type 2 Abs).

• Participants testing positive for COVID-19 prior to dosing.

• Any cardiac abnormalities.

• A CAP activity < 60% at screening.

• Known or suspected history of drug abuse, history of alcohol abuse or smoking.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• AZD6912
AZD6912 will be administered as a single sub-cutaneous dose.
• Placebo
Placebo will be administered as a single sub-cutaneous dose.

Locations

Country	Name	City	State
Canada	Research Site	Montréal	Quebec
United Kingdom	Research Site	Harrow

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs)	To assess the safety and tolerability of AZD6912 in healthy participants.	From screening (Day -70) to last follow up visit (Day 197- approximately 38 weeks)
Secondary	Maximum observed plasma (peak) drug concentration (Cmax) of AZD6912	To characterise the Cmax of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Area under plasma concentration-time curve from zero to infinity (AUCinf) of AZD6912	To characterise AUCinf of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD6912	To characterise the AUClast of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD6912	To characterise tmax of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Time of last measurable concentration (tlast) of AZD6912	To characterise tlast of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Terminal elimination half-life (t½?z) of AZD6912	To characterise t½?z of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Dose normalised AUClast (AUClast/D) of AZD6912	To characterise AUClast/D of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Dose normalised AUCinf (AUCinf/D) of AZD6912	To characterise AUCinf/D of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Dose normalised Cmax (Cmax/D) of AZD6912	To characterise Cmax/D of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD6912	To characterise CL/F of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) of AZD6912	To characterise Vz/F of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Percent change from baseline in plasma concentrations of Complement factor B (CFB) protein	To assess the PD effects of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Percent change from baseline in serum of Complement functional activity (CAP)	To assess the PD effects of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
Secondary	Number of participants with positive Anti-Drug Anitbody (ADA)	To evaluate the immunogenicity of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)