A Phase 2 interventional study of Placebo and ISIS 757456 in Hypertension, sponsored by Ionis Pharmaceuticals, Inc.. Completed at 9 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-01-18.
Sponsored by Ionis Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment
This study evaluated the effect of ISIS 757456 (IONIS-AGT-LRx) on plasma angiotensinogen (AGT) and systolic blood pressure (SBP) in uncontrolled hypertensive participants who were on two to three antihypertensive medications.
This study was a Phase 2, double-blind, randomized, placebo-controlled study in 26 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or placebo, with an additional loading dose administered on Study Day 3. The treatment lasted for 8 weeks and the post-treatment period lasted for 13 weeks.
6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.
This study's enrollment of 26 is below the median of 90 across 4,995 interventional studies indexed under Hypertension.
Browse Hypertension studies →Ionis Pharmaceuticals, Inc. is the lead sponsor of 116 studies on the registry; 10 are open to participants now.
Of its 48 completed or terminated interventional studies of FDA-regulated products, 21 (44%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
The use of the following at time of screening and during the course of the study:
Unstable/underlying cardiovascular disease defined as:
Participants received ISIS 757456-matching placebo, subcutaneous (SC) injection, once-weekly for 8 weeks and an additional loading dose on Day 3.
Drug: Placebo
Participants received ISIS 757456 80 mg, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3.
Drug: ISIS 757456
ISIS 757456-matching placebo solution administered as SC injection.
ISIS 757456 administered as SC injection.
Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
Time frame: Baseline up to Day 57 (start of Week 9)
Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141
Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141
Participants took part in the study at 9 investigative sites from 13 November 2019 to 20 July 2020.
| Milestone | Placebo | ISIS 757456 |
|---|---|---|
| Started | 8 | 18 |
| Completed | 8 | 16 |
| Not completed | 0 | 2 |
| Withdrew: Voluntary withdrawal | 0 | 1 |
| Withdrew: Reason not specified | 0 | 1 |
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
| percent change | Placebo | ISIS 757456 |
|---|---|---|
| Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo | -3.4 ± 17.8 | -67.4 ± 14.1 |
| mmHg | Placebo | ISIS 757456 |
|---|---|---|
| Baseline | 152 ± 8 | 153 ± 10 |
| Change From Baseline at Day 3 | -6 ± 15 | -12 ± 14 |
| Change From Baseline at Day 8 | -8 ± 9 | -14 ± 15 |
| Change From Baseline at Day 15 | -0 ± 16 | -9 ± 13 |
| Change From Baseline at Day 22 | -8 ± 15 | -8 ± 16 |
| Change From Baseline at Day 29 | 3 ± 14 | -8 ± 16 |
| Change From Baseline at Day 36 | 0 ± 15 | -13 ± 15 |
| Change From Baseline at Day 43 | -2 ± 9 | -11 ± 12 |
| Change From Baseline at Day 50 | -3 ± 12 | -17 ± 16 |
| Change From Baseline at Day 57 | -5 ± 10 | -12 ± 16 |
| Change From Baseline at Day 64 | -8 ± 16 | -16 ± 11 |
| Change From Baseline at Day 78 | -8 ± 14 | -12 ± 13 |
| Change From Baseline at Day 92 | -5 ± 13 | -15 ± 15 |
| Change From Baseline at Day 120 | -3 ± 10 | -10 ± 14 |
| Change From Baseline at Day 141 | 0 ± 13 | -11 ± 13 |
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug
| ug/mL | Placebo | ISIS 757456 |
|---|---|---|
| Baseline | 25.5 ± 4.4 | 25.2 ± 3.4 |
| Change From Baseline at Day 3 | -1.7 ± 2.3 | -2.5 ± 4.2 |
| Change From Baseline at Day 8 | -1.5 ± 3.1 | -9.6 ± 4.3 |
| Change From Baseline at Day 15 | -1.6 ± 2.1 | -13.4 ± 5.7 |
| Change From Baseline at Day 22 | -0.7 ± 1.6 | -15.7 ± 4.7 |
| Change From Baseline at Day 29 | -0.8 ± 3.9 | -17.1 ± 4.0 |
| Change From Baseline at Day 36 | -2.0 ± 2.6 | -17.2 ± 4.0 |
| Change From Baseline at Day 43 | -2.9 ± 2.5 | -17.5 ± 3.7 |
| Change From Baseline at Day 50 | -2.2 ± 3.2 | -17.7 ± 3.8 |
| Change From Baseline at Day 57 | -1.1 ± 4.5 | -17.0 ± 4.1 |
| Change From Baseline at Day 64 | -4.3 ± 3.7 | -15.9 ± 3.7 |
| Change From Baseline at Day 78 | -3.0 ± 3.1 | -12.9 ± 3.9 |
| Change From Baseline at Day 92 | -1.7 ± 3.9 | -9.8 ± 4.2 |
| Change From Baseline at Day 120 | -3.1 ± 1.9 | -5.7 ± 4.0 |
| Change From Baseline at Day 141 | -3.4 ± 4.7 | -5.8 ± 5.3 |
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
| percent change | Placebo | ISIS 757456 |
|---|---|---|
| Percent Change From Baseline at Day 3 | -6.6 ± 9.5 | -10.3 ± 16.6 |
| Percent Change From Baseline at Day 8 | -4.8 ± 12.9 | -38.5 ± 16.6 |
| Percent Change From Baseline at Day 15 | -6.6 ± 8.1 | -53.3 ± 22.1 |
| Percent Change From Baseline at Day 22 | -2.4 ± 6.3 | -62.4 ± 17.9 |
| Percent Change From Baseline at Day 29 | -2.8 ± 15.5 | -67.9 ± 13.5 |
| Percent Change From Baseline at Day 36 | -8.1 ± 10.2 | -68.4 ± 13.9 |
| Percent Change From Baseline at Day 43 | -10.6 ± 8.2 | -69.5 ± 11.3 |
| Percent Change From Baseline at Day 50 | -7.9 ± 11.4 | -70.3 ± 11.1 |
| Percent Change From Baseline at Day 64 | -18.0 ± 15.5 | -63.5 ± 14.0 |
| Percent Change From Baseline at Day 78 | -12.3 ± 12.2 | -51.1 ± 14.5 |
| Percent Change From Baseline at Day 92 | -6.6 ± 14.5 | -38.9 ± 15.7 |
| Percent Change From Baseline at Day 120 | -12.4 ± 7.7 | -22.1 ± 14.9 |
| Percent Change From Baseline at Day 141 | -14.3 ± 17.4 | -22.3 ± 19.8 |
Collected over From signing of informed consent up to end of post-treatment period (Day 141). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/8 (0%) | 0/8 (0%) | 3/8 (37.5%) |
| ISIS 757456 | 0/18 (0%) | 0/18 (0%) | 6/18 (33.3%) |
| Event | Placebo | ISIS 757456 |
|---|---|---|
| Abdominal discomfortGastrointestinal disorders | 1/8 | 0/18 |
| DiarrhoeaGastrointestinal disorders | 1/8 | 0/18 |
| DyspepsiaGastrointestinal disorders | 1/8 | 0/18 |
| NauseaGastrointestinal disorders | 1/8 | 0/18 |
| ChillsGeneral disorders | 1/8 | 0/18 |
| ConfusionInjury, poisoning and procedural complications | 1/8 | 0/18 |
| Diabetes mellitusMetabolism and nutrition disorders | 1/8 | 0/18 |
| ArthritisMusculoskeletal and connective tissue disorders | 1/8 | 0/18 |
| Back painMusculoskeletal and connective tissue disorders | 1/8 | 0/18 |
| Musculoskeletal chest painMusculoskeletal and connective tissue disorders | 1/8 | 0/18 |
Safety set included all participants who were randomized and received at least 1 dose of study drug.
| Age, Continuous(years) | Placebo | ISIS 757456 | Total |
|---|---|---|---|
| Mean | 61 ± 10 | 60 ± 8 | 60 ± 9 |
| Sex: Female, Male(Participants) | Placebo | ISIS 757456 | Total |
|---|---|---|---|
| Female | 6 | 14 | 20 |
| Male | 2 | 4 | 6 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | ISIS 757456 | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 8 | 10 |
| Not Hispanic or Latino | 6 | 10 | 16 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Placebo | ISIS 757456 | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 4 | 3 | 7 |
| White | 4 | 15 | 19 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Plasma Angiotensinogen (AGT)(micrograms per milliliter (μg/mL)) | Placebo | ISIS 757456 | Total |
|---|---|---|---|
| Mean | 25.5 ± 4.4 | 25.2 ± 3.4 | 25.3 ± 3.7 |
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Ionis Pharmaceuticals, Inc.