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

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

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

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: AZD6912; Drug: Placebo

Detailed 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.

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

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3P 3P1
      • Recruiting
      • Research Site
• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD6912 Dose 1; Participants will receive AZD6912 Dose 1.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 Dose 2; Participants will receive AZD6912 Dose 2.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 Dose 3; Participants will receive AZD6912 Dose 3.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 Dose 4; Participants will receive AZD6912 Dose 4.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 Dose 5; Participants will receive AZD6912 Dose 5.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 Dose 6; Participants will receive AZD6912 Dose 6.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Placebo Comparator: Placebo; Participants will receive Placebo.	Drug: Placebo; Placebo will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 additional cohort 1 -including Japanese Participants; Participants will receive AZD6912.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.
Experimental: AZD6912 additional cohort 2 -including Japanese Participants; Participants will receive AZD6912.	Drug: AZD6912; AZD6912 will be administered as a single sub-cutaneous dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
Terminal elimination half-life (t½λz) of AZD6912	To characterise t½λz of single ascending doses of AZD6912 in healthy participants.	From randomization to Day 197 (up to 28 weeks)
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)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): June 27, 2025
• Study Completion (Estimated): June 27, 2025

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Complement factor B; Small interfering ribonucleic acid; CFB messenger ribonucleic acid
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: D7130C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No