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

Phase 1

Active, not recruiting

• Conditions: Mild Hypertension
• Interventions: Drug: QCZ484; Drug: Placebo

• Registration Number: NCT06905327
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

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 Timeline

• Study Start: 2023-03-08
• Primary Completion: 2024-09-25
• Status Verified: 2025-03
• Study First Submitted: 2025-03-25
• Study First Submitted QC: 2025-03-25
• Last Update Submitted: 2025-03-25
• Study First Posted: 2025-04-01
• Last Update Posted: 2025-04-01
• Study Completion: 2025-08-14

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 56

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: QCZ484 50 mg	QCZ484	Healthy Cohort: single dose
Part A: QCZ484 150 mg	QCZ484	Healthy Cohort: single dose
Part A: QCZ484 300 mg	QCZ484	Healthy Cohort: single dose
Part A: QCZ484 600 mg	QCZ484	Healthy Cohort: single dose
Part A: QCZ484 Placebo	Placebo	Healthy Cohort: single dose
Part B: QCZ484 150 mg	QCZ484	Hypertension Cohort: single dose
Part B: QCZ484 300 mg	QCZ484	Hypertension Cohort: single dose
Part B: QCZ484 600 mg	QCZ484	Hypertension Cohort: single dose
Part B: QCZ484 Placebo	Placebo	Hypertension Cohort: single dose

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇳🇿 Auckland, New Zealand