A Study to Evaluate the Safety of QCZ484 in Healthy and Mild Hypertensive Subjects

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered QCZ484 in Healthy Subjects and Subjects With Mild Hypertension

This is a randomized, double-blind, placebo-controlled study including Part A single ascending dose (SAD) in healthy subjects and Part B single dose in subjects with mild hypertension.

Study Overview

• Status: Completed
• Conditions: Mild Hypertension
• Intervention / Treatment: Drug: QCZ484; Drug: Placebo

Detailed Description

Phase 1, multicenter, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of QCZ484. In Part A, single ascending doses of QCZ484 are tested in healthy subjects, while in Part B, single doses of QCZ484 are tested in subjects with mild hypertension. One dose of QCZ484 is administered subcutaneously.

This study was started by Argo Biopharma, and global sponsorship was transferred to Novartis.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Novartis Investigative Site
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Novartis Investigative Site
    • Morayfield, Queensland, Australia, 4506
      • Novartis Investigative Site
• New Zealand
  • Auckland, New Zealand, 0622
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy males or females aged 18 to 60 years, inclusive, at the time of informed consent. (Part A only).
• Males or females aged 18 to 72 years, inclusive, at the time of informed consent (Part B only).
• Body mass index (BMI) >= 18 and <= 32 kg/m2 and body weight >50 kg (Part A only).
• Body mass index (BMI) >=18 and <=35 kg/m2 and body weight >50 kg (Part B only).
• Triplicate 12-lead electrocardiogram (ECG) after >5 minutes resting without clinically significant findings at screening and Day -1.
• Mean sitting systolic blood pressure (SBP) of >=130 and <160 mm Hg (Part B only).

Exclusion Criteria:

• History of hypotension or orthostatic hypotension.
• History of syncope within 1 year.
• SBP <90 mmHg or DBP <60 mm Hg at screening (Part A only).
• Clinical laboratory findings outside of range are deemed clinically significant by the investigator at screening.
• Any liver function panel analyte value > 1.2 ×upper limits of normal (ULN) at screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: QCZ484 50 mg; Healthy Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Experimental: Part A: QCZ484 150 mg; Healthy Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Experimental: Part A: QCZ484 300 mg; Healthy Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Experimental: Part A: QCZ484 600 mg; Healthy Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Placebo Comparator: Part A: QCZ484 Placebo; Healthy Cohort: single dose	Drug: Placebo; via subcutaneous injection
Experimental: Part B: QCZ484 150 mg; Hypertension Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Experimental: Part B: QCZ484 300 mg; Hypertension Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Experimental: Part B: QCZ484 600 mg; Hypertension Cohort: single dose	Drug: QCZ484; doses of 50, 150, 300 or 600 mg via subcutaneous injection
Placebo Comparator: Part B: QCZ484 Placebo; Hypertension Cohort: single dose	Drug: Placebo; via subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AEs)	Overall number of AEs, severity, and relationship to study treatment per treatment group.	Part A: up to 12 weeks post dose. Part B: up to 8 weeks post dose.
Number of participants with abnormalities in any laboratory parameter	Safety laboratory data (blood chemistry, hematology, coagulation, and urinalysis)	Part A: up to 12 weeks post dose. Part B: up to 8 weeks post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of AEs	Overall number of AEs, severity and relationship to study treatment per treatment group	up to 48 weeks post dose
Number of participants with abnormalities in any laboratory parameter	Safety laboratory data (blood chemistry, hematology, coagulation, and urinalysis)	up to 48 weeks post dose
Plasma pharmacokinetics of QCZ484 and metabolites - Cmax	Measured by Cmax - The maximum plasma concentration of QCZ484 and of potential metabolites	Day 1; up to Day 8
Plasma pharmacokinetics of QCZ484 - Tmax	Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of QCZ484	Day 1; up to Day 8
Plasma pharmacokinetics of QCZ484 and metabolites - AUC0-48	Measured by AUC - Area under the curve versus time curve of QCZ484 from 0 to 48 hours (AUC0-48) and of potential metabolites	Day 1; up to Day 8
Plasma pharmacokinetics of QCZ484 - AUC0-inf	Measured by AUC - Area under the curve versus time curve of QCZ484 from 0 to infinity (AUC0-inf)	Day 1; up to Day 8
Plasma pharmacokinetics of QCZ484 - T1/2	Measured by T1/2 - The elimination half-life of QCZ484	Day 1; up to Day 8
Urine pharmacokinetics of QCZ484	Measured by urine concentration of QCZ484 up to 24 hours post dose	Day 1; up to Day 2
Change from baseline in serum angiotensinogen (AGT) level	Measured by serum AGT level	up to 48 weeks post dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2023
• Primary Completion (Actual): September 25, 2024
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; QCZ484
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: CQCZ484A02101; BW-00163-1002 (Other Identifier: Argo Biopharma)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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