Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously to Hypertensive Participants With Controlled Blood Pressure (NCT NCT03714776)
NCT ID: NCT03714776
Last Updated: 2023-01-06
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Baseline, Week 7
Results posted on
2023-01-06
Participant Flow
Participants took part in the study at 5 investigative sites in the United States from 03 January 2019 to 13 November 2019.
A total of 77 participants were screened of which 25 were enrolled and randomized to receive study drug.
Participant milestones
| Measure |
Placebo
Placebo matching solution injected subcutaneously (SC) once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
17
|
|
Overall Study
Safety Set
|
8
|
17
|
|
Overall Study
Full Analysis Set (FAS)
|
8
|
17
|
|
Overall Study
Per Protocol Set (PPS)
|
6
|
15
|
|
Overall Study
COMPLETED
|
8
|
17
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PPS: All FAS(all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
Baseline characteristics by cohort
| Measure |
Placebo
n=8 Participants
Placebo matching solution injected SC once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
n=17 Participants
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57 years
STANDARD_DEVIATION 4 • n=8 Participants
|
60 years
STANDARD_DEVIATION 7 • n=17 Participants
|
59 years
STANDARD_DEVIATION 7 • n=25 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=8 Participants
|
7 Participants
n=17 Participants
|
13 Participants
n=25 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=8 Participants
|
10 Participants
n=17 Participants
|
12 Participants
n=25 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=8 Participants
|
8 Participants
n=17 Participants
|
10 Participants
n=25 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=8 Participants
|
9 Participants
n=17 Participants
|
15 Participants
n=25 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
0 Participants
n=17 Participants
|
0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=8 Participants
|
0 Participants
n=17 Participants
|
0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=8 Participants
|
1 Participants
n=17 Participants
|
1 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=8 Participants
|
0 Participants
n=17 Participants
|
0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=8 Participants
|
5 Participants
n=17 Participants
|
7 Participants
n=25 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=8 Participants
|
10 Participants
n=17 Participants
|
15 Participants
n=25 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=8 Participants
|
1 Participants
n=17 Participants
|
2 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
0 Participants
n=17 Participants
|
0 Participants
n=25 Participants
|
|
Plasma Angiotensinogen (AGT) Concentration
|
19.5 micrograms per milliliter (μg/mL)
n=6 Participants • PPS: All FAS(all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
|
20.3 micrograms per milliliter (μg/mL)
n=15 Participants • PPS: All FAS(all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
|
19.9 micrograms per milliliter (μg/mL)
n=21 Participants • PPS: All FAS(all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
|
|
In-clinic Systolic Blood Pressure (SBP)
|
148 millimeters of mercury (mmHg)
n=6 Participants • PPS: All FAS (all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
|
145 millimeters of mercury (mmHg)
n=15 Participants • PPS: All FAS (all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
|
145.9 millimeters of mercury (mmHg)
n=21 Participants • PPS: All FAS (all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) participants who received at least 5 of the 7 doses of study drug, did not receive antihypertensive medications during Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
|
PRIMARY outcome
Timeframe: Baseline, Week 7Population: PPS included all FAS participants (all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) who received at least 5 of the 7 doses of the study drug, did not receive antihypertensive medications during the Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo matching solution injected SC once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
n=15 Participants
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
|---|---|---|
|
Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 43 (Week 7) Compared to Placebo
|
12.6 percent change
Standard Deviation 23.3
|
-54.2 percent change
Standard Deviation 24.8
|
SECONDARY outcome
Timeframe: Baseline, Days 3, 8, 15, 22, 29, and 36Population: PPS=all FAS participants(all randomized participants who received at least 1 injection of study drug and had at least 1 post-Baseline efficacy or exploratory measurements)who received at least 5 of 7 doses of study drug, did not receive antihypertensive medications during Treatment Period prior to Day 43, had no significant protocol deviations that would have been expected to affect efficacy assessments. Number analyzed=number of participants with data available for analysis at given time point.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo matching solution injected SC once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
n=15 Participants
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
|---|---|---|
|
Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
Change From Baseline at Day 3
|
-10 mmHg
Standard Deviation 4
|
-7 mmHg
Standard Deviation 10
|
|
Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
Change From Baseline at Day 8
|
-6 mmHg
Standard Deviation 18
|
-5 mmHg
Standard Deviation 12
|
|
Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
Change From Baseline at Day 15
|
-14 mmHg
Standard Deviation 10
|
-4 mmHg
Standard Deviation 14
|
|
Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
Change From Baseline at Day 22
|
-10 mmHg
Standard Deviation 12
|
-7 mmHg
Standard Deviation 14
|
|
Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
Change From Baseline at Day 29
|
-1 mmHg
Standard Deviation 13
|
-5 mmHg
Standard Deviation 11
|
|
Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
Change From Baseline at Day 36
|
-3 mmHg
Standard Deviation 10
|
-8 mmHg
Standard Deviation 13
|
SECONDARY outcome
Timeframe: Baseline, Days 3, 8, 15, 22, 29, and 36Population: PPS=all FAS participants(all randomized participants who received at least 1 injection of study drug and had at least 1 post-Baseline efficacy or exploratory measurements)who received at least 5 of 7 doses of study drug, did not receive antihypertensive medications during Treatment Period prior to Day 43, had no significant protocol deviations that would have been expected to affect efficacy assessments. Number analyzed=number of participants with data available for analysis at given time point.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo matching solution injected SC once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
n=15 Participants
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
|---|---|---|
|
Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
Percent Change From Baseline at Day 3
|
6.8 percent change
Standard Deviation 20.5
|
-8.3 percent change
Standard Deviation 13.8
|
|
Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
Percent Change From Baseline at Day 8
|
19.1 percent change
Standard Deviation 23.8
|
-35.7 percent change
Standard Deviation 13.8
|
|
Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
Percent Change From Baseline at Day 15
|
7.6 percent change
Standard Deviation 28.2
|
-50.4 percent change
Standard Deviation 16.4
|
|
Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
Percent Change From Baseline at Day 22
|
8.7 percent change
Standard Deviation 24.0
|
-52.4 percent change
Standard Deviation 17.3
|
|
Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
Percent Change From Baseline at Day 29
|
6.1 percent change
Standard Deviation 13.8
|
-62.2 percent change
Standard Deviation 10.5
|
|
Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
Percent Change From Baseline at Day 36
|
2.9 percent change
Standard Deviation 27.7
|
-58.3 percent change
Standard Deviation 12.9
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
ISIS 757456 80 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=8 participants at risk
Placebo matching solution injected SC once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
n=17 participants at risk
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
|---|---|---|
|
Gastrointestinal disorders
Pancreatitis acute
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Placebo
n=8 participants at risk
Placebo matching solution injected SC once weekly for up to 6 weeks and an additional loading dose on Day 3.
|
ISIS 757456 80 mg
n=17 participants at risk
ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.
|
|---|---|---|
|
General disorders
Injection site erythema
|
0.00%
0/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
11.8%
2/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Chills
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Injection site haemorrhage
|
0.00%
0/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
5.9%
1/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Injection site rash
|
0.00%
0/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
5.9%
1/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Injection site swelling
|
0.00%
0/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
5.9%
1/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
2/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
25.0%
2/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
17.6%
3/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Abdominal distension
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
5.9%
1/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Perivascular dermatitis
|
0.00%
0/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
5.9%
1/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
5.9%
1/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Investigations
Blood glucose increased
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Psychiatric disorders
Insomnia
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
|
Renal and urinary disorders
Haematuria
|
12.5%
1/8 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/17 • Up to Week 19
Safety Set included all participants who were randomized and received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER