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

Sponsor
Alnylam Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04936035
Collaborator
(none)
375
93
5
40.8
4
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
375 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 7, 2021
Anticipated Primary Completion Date :
Apr 1, 2023
Anticipated Study Completion Date :
Dec 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: ALN-AGT01 Dose Regimen 1

Multiple doses of ALN-AGT01 administered by subcutaneous (SC) injection during the 12-month DB treatment period.

Drug: ALN-AGT01
ALN-AGT01 administered by SC injection

Experimental: ALN-AGT01 Dose Regimen 2

Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.

Drug: ALN-AGT01
ALN-AGT01 administered by SC injection

Experimental: ALN-AGT01 Dose Regimen 3

Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.

Drug: ALN-AGT01
ALN-AGT01 administered by SC injection

Experimental: ALN-AGT01 Dose Regimen 4

Multiple doses of ALN-AGT01 administered by SC injection during the 12-month DB treatment period.

Drug: ALN-AGT01
ALN-AGT01 administered by SC injection

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.

Drug: Placebo
Placebo administered by SC injection

Drug: ALN-AGT01
ALN-AGT01 administered by SC injection

Outcome Measures

Primary Outcome Measures

  1. Change from Baseline at Month 3 in 24-hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM) [Baseline and Month 3]

Secondary Outcome Measures

  1. Change from Baseline at Months 3 and 6 in Office SBP [Baseline and Months 3 and 6]

  2. Change from Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM [Baseline and Month 6]

  3. 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 [Baseline and Month 6]

  4. Time-adjusted Change from Baseline in 24-hour Mean SBP and Diastolic Blood Pressure (DBP), Assessed by ABPM [Baseline through Month 6]

  5. Change from Baseline in 24-hour mean DBP, Assessed by ABPM [Baseline and Month 6]

  6. Change from Baseline in Office SBP and DBP [Baseline and Month 6]

  7. Change in Serum Angiotensinogen (AGT [Baseline through Month 6]

  8. Change from Baseline in Daytime and Nighttime SBP and DBP by ABPM (Including Dipping Pattern) [Baseline and Month 6]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Clinical Trial Site Birmingham Alabama United States 35209
2 Clinical Trial Site Glendale Arizona United States 85308
3 Clinical Trial Site Tempe Arizona United States 85281
4 Clinical Trial Site Tempe Arizona United States 85282
5 Clinical Trial Site La Mesa California United States 91942
6 Clinical Trial Site Los Angeles California United States 90057
7 Clinical Trial Site Montclair California United States 91763
8 Clinical Trial Site S. Gate California United States 90280
9 Clinical Trial Site San Diego California United States 92103
10 Clinical Trial Site Vista California United States 92083
11 Clinical Trial Site Clearwater Florida United States 33756
12 Clinical Trial Site Coral Gables Florida United States 33134
13 Clinical Trial Site Fleming Island Florida United States 32003
14 Clinical Trial Site Hollywood Florida United States 33024
15 Clinical Trial Site Inverness Florida United States 34452
16 Clinical Trial Site Jacksonville Florida United States 32204
17 Clinical Trial Site Jacksonville Florida United States 32216
18 Clinical Trial Site Jacksonville Florida United States 32256
19 Clinical Trial Site Miami Florida United States 33126
20 Clinical Trial Site Miami Florida United States 33135
21 Clinical Trial Site Naples Florida United States 34102
22 Clinical Trial Site Orlando Florida United States 32801
23 Clinical Trial Site Acworth Georgia United States 30101
24 Clinical Trial Site Columbus Georgia United States 31904
25 Clinical Trial Site Fayetteville Georgia United States 30214
26 Clinical Trial Site Macon Georgia United States 31210
27 Clinical Trial Site Savannah Georgia United States 31406
28 Clinical Trial Site Snellville Georgia United States 30078
29 Clinical Trial Site Champaign Illinois United States 61822
30 Clinical Trial Site Quincy Illinois United States 62301
31 Clinical Trial Site River Forest Illinois United States 60305
32 Clinical Trial Site Franklin Indiana United States 46131
33 Clinical Trial Site Greenfield Indiana United States 46140
34 Clinical Trial Site Valparaiso Indiana United States 46383
35 Clinical Trial Site West Des Moines Iowa United States 50266
36 Clinical Trial Site Versailles Kentucky United States 40383
37 Clinical Trial Site Lake Charles Louisiana United States 70601
38 Clinical Trial Site New Orleans Louisiana United States 70124
39 Clinical Trial Site Prairieville Louisiana United States 70769
40 Clinical Trial Site Baltimore Maryland United States 21229
41 Clinical Trial Site Jefferson City Missouri United States 65109
42 Clinical Trial Site Henderson Nevada United States 89052
43 Clinical Trial Site Las Vegas Nevada United States 89119
44 Clinical Trial Site Berlin New Jersey United States 08009
45 Clinical Trial Site Bronx New York United States 10456
46 Clinical Trial Site New York New York United States 10036
47 Clinical Trial Site Greensboro North Carolina United States 27408
48 Clinical Trial Site Greensboro North Carolina United States 27410
49 Clinical Trial Site Wilmington North Carolina United States 28401
50 Clinical Trial Site Tulsa Oklahoma United States 74135
51 Clinical Trial Site Medford Oregon United States 97504
52 Clinical Trial Site Greenville South Carolina United States 29607
53 Clinical Trial Site Rock Hill South Carolina United States 29732
54 Clinical Trial Site Spartanburg South Carolina United States 29303
55 Clinical Trial Site Memphis Tennessee United States 38119
56 Clinical Trial Site Carrollton Texas United States 75010
57 Clinical Trial Site Cedar Park Texas United States 78613
58 Clinical Trial Site Dallas Texas United States 75234
59 Clinical Trial Site Dallas Texas United States 75251
60 Clinical Trial Site Houston Texas United States 77074
61 Clinical Trial Site Houston Texas United States 77081
62 Clinical Trial Site Magnolia Texas United States 77355
63 Clinical Trial Site Pearland Texas United States 77584
64 Clinical Trial Site San Antonio Texas United States 78229
65 Clinical Trial Site Stephenville Texas United States 76401
66 Clinical Trial Site Sugar Land Texas United States 77478
67 Clinical Trial Site Tomball Texas United States 77375
68 Clinical Trial Site Waco Texas United States 76708
69 Clinical Trial Site Appomattox Virginia United States 24522
70 Clinical Trial Site Burke Virginia United States 22015
71 Clinical Trial Site Brampton Ontario Canada
72 Clinical Trial Site London Ontario Canada
73 Clinical Trial Site Toronto Ontario Canada
74 Clinical Trial Site Chicoutimi Quebec Canada
75 Clinical Trial Site Mirabel Quebec Canada
76 Clinical Trial Site Montréal Quebec Canada
77 Clinical Trial Site Quebec City Quebec Canada
78 Clinical Trial Site Trois-Rivières Quebec Canada
79 Clinical Trial Site Victoriaville Quebec Canada
80 Clinical Trial Site San Juan Puerto Rico
81 Clinical Trial Site Ivano-Frankivs'k Ukraine
82 Clinical Trial Site Kharkiv Ukraine
83 Clinical Trial Site Kyiv Ukraine
84 Clinical Trial Site Lviv Ukraine
85 Clinical Trial Site Odesa Ukraine
86 Clinical Trial Site Vinnytsia Ukraine
87 Clinical Trial Site Zaporizhzhia Ukraine
88 Clinical Trial Site Úzhgorod Ukraine
89 Clinical Trial Site Chorley United Kingdom
90 Clinical Trial Site Glasgow United Kingdom
91 Clinical Trial Site Hexham United Kingdom
92 Clinical Trial Site London United Kingdom
93 Clinical Trial Site Manchester United Kingdom

Sponsors and Collaborators

  • Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04936035
Other Study ID Numbers:
  • ALN-AGT01-002
  • 2021-001248-82
First Posted:
Jun 23, 2021
Last Update Posted:
Aug 17, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Alnylam Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 17, 2022