A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension (KARDIA-1)

• ClinicalTrials.gov Identifier: NCT04936035
• Recruitment Status: Active, not recruiting
• First Posted: June 23, 2021
• Last Update Posted: May 13, 2024
• Sponsor: Alnylam Pharmaceuticals
• Information provided by (Responsible Party): Alnylam Pharmaceuticals

Tracking Information

• First Submitted Date: June 14, 2021
• First Posted Date: June 23, 2021
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: July 7, 2021
• Actual Primary Completion Date: April 4, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 26, 2022): Change from Baseline at Month 3 in 24-hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: Baseline and Month 3 ]
• Original Primary Outcome Measures (submitted: June 14, 2021): Change in Systolic Blood Pressure (SBP) from Baseline to Month 3, Assessed by Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: Baseline and Month 3 ]

Current Secondary Outcome Measures (submitted: February 2, 2023)

• Change from Baseline at Month 3 in Office SBP [ Time Frame: Baseline and Month 3 ]
• Change from Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
• Change from Baseline at Month 6 in Office SBP [ Time Frame: Baseline through Month 6 ]
• Proportion of Patients with 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction ≥20 mmHg without Additional Antihypertensive Medications at Month 6 [ Time Frame: Baseline through Month 6 ]
• Time-adjusted Change from Baseline in 24-hour Mean SBP and Diastolic Blood Pressure (DBP), Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
• Change from Baseline in 24-hour mean DBP, Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
• Change from Baseline in Office SBP and DBP [ Time Frame: Baseline through Month 6 ]
• Change in Serum Angiotensinogen (AGT) [ Time Frame: Baseline through Month 6 ]
• Change from Baseline in Daytime and Nighttime SBP and DBP by ABPM (Including Dipping Pattern) [ Time Frame: Baseline through Month 6 ]

Original Secondary Outcome Measures (submitted: June 14, 2021)

• Change in SBP from Baseline to Month 6, Assessed by ABPM [ Time Frame: Baseline through Month 6 ]
• Change in Diastolic Blood Pressure (DBP) from Baseline to Month 3 and Month 6, Assessed by ABPM [ Time Frame: Baseline through Months 3 and 6 ]
• Change in Office SBP from Baseline Through Month 6 [ Time Frame: Baseline through Month 6 ]
• Change in Office DBP from Baseline Through Month 6 [ Time Frame: Baseline through Month 6 ]
• Change in Serum Angiotensinogen (AGT) from Baseline Through Month 6 [ Time Frame: Baseline through Month 6 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension
• Official Title: A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Multicenter Study to Evaluate the Efficacy and Safety of ALN-AGT01 in Patients With Mild-to-Moderate Hypertension
• Brief Summary: The purpose of this study is to evaluate the effect of ALN-AGT01 on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of ALN-AGT01.
• Detailed Description: Participants will receive ALN-AGT01 or placebo for the first 6 months of the 12-month double-blind (DB) treatment period. Participants randomized to placebo will be re-randomized at Month 6 to 1 of the 4 initial ALN-AGT01 regimens until the end of the 12-month DB treatment period. Participants randomized to ALN-AGT01 regimens will remain on their originally assigned regimens through remainder of the study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: Placebo
  Placebo administered by SC injection
• Drug: ALN-AGT01
  ALN-AGT01 administered by SC injection
  Other Name: Zilebesiran

Study Arms

• Experimental: ALN-AGT01 Dose Regimen 1
  Multiple doses of ALN-AGT01 administered by subcutaneous (SC) injection during the 12-month DB treatment period.
  Intervention: Drug: ALN-AGT01
• Experimental: ALN-AGT01 Dose Regimen 2
  Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.
  Intervention: Drug: ALN-AGT01
• Experimental: ALN-AGT01 Dose Regimen 3
  Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.
  Intervention: Drug: ALN-AGT01
• Experimental: ALN-AGT01 Dose Regimen 4
  Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.
  Intervention: Drug: ALN-AGT01
• Placebo Comparator: Placebo + ALN-AGT01
  Multiple doses of placebo administered by SC injection during the first 6 months of 12-month DB treatment period, followed by multiple doses of ALN-AGT01 administered by SC injection during the last 6 months of the 12-month DB treatment period.
  Interventions:

  • Drug: Placebo
  • Drug: ALN-AGT01

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 2, 2023): 394
• Original Estimated Enrollment (submitted: June 14, 2021): 375
• Estimated Study Completion Date: December 4, 2024
• Actual Primary Completion Date: April 4, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication

Exclusion Criteria:

• Secondary hypertension, orthostatic hypotension
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upper limit of normal (ULN)
• Elevated potassium >5 mEq/L
• Estimated glomerular filtration rate (eGFR) of ≤30 mL/min/1.73m^2
• Received an investigational agent within the last 30 days
• Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus, newly diagnosed Type 2 diabetes mellitus
• History of any cardiovascular event within 6 months prior to randomization
• History of intolerance to SC injection(s)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Puerto Rico, Ukraine, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT04936035
• Other Study ID Numbers: ALN-AGT01-002; 2021-001248-82 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.

Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.

• Current Responsible Party: Alnylam Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Alnylam Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Alnylam Pharmaceuticals

• PRS Account: Alnylam Pharmaceuticals
• Verification Date: May 2024