E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the add-on effect of zilebesiran on Systolic Blood Pressure (SBP) as assessed by ambulatory blood pressure monitoring(ABPM) at Month 3 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the add-on effect of zilebesiran on blood pressure assessed by ABPM - To evaluate the add-on effect of zilebesiran on office blood pressure - To characterize the pharmacodynamic effects of zilebesiran |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Age 18 to 75 years -24-hour mean SBP >130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in on protocol-specified background antihypertensive medication
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E.4 | Principal exclusion criteria |
-Secondary hypertension, orthostatic hypotension -Elevated potassium >5 mEq/L -eGFR of ≤30 mL/min/1.73m2 -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 subcutaneous injection(s) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in 24-hour mean SBP from baseline to Month 3, assessed by ABPM |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in office SBP from baseline to Month 3 - Change in 24-hour mean SBP from baseline to Month 6, assessed by ABPM - Change in office SBP from baseline to Month 6 - Change in 24-hour mean diastolic blood pressure from baseline to Months 3 and 6, assessed by ABPM - Change in office DBP from baseline to Months 3 and 6 - Change in daytime and nighttime mean SBP and DBP(diastolic blood pressure) from baseline to Month 3 and Month 6, assessed by ABPM - Change in serum AGT |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Change in office SBP from baseline to Month 3: Baseline, Week 2, Months 1, 2 and 3 - Change in 24-hour mean SBP from baseline to Month 6, assessed by ABPM: Baseline, Months 2, 3 and 6 - Change in office SBP from baseline to Month 6: Baseline, Week 2, Months 1-6 - Change in 24-hour mean DBP from baseline to Months 3 and 6, assessed by ABPM: Baseline, Months 2, 3 and 6 - Change in office DBP from baseline to Months 3 and 6: Screening, Run-In period, Week 2, Months 1-6 - Change in daytime and nighttime mean SBP and DBP from baseline to Month 3 and Month 6, assessed by ABPM: Baseline, Months 2, 3 and 6 - Change in serum AGT: Baseline, Week 2, Months 1-9, Month 12 & Month 18 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Add-on to standard of care antihypertensive treatment |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Estonia |
Latvia |
Lithuania |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as the last patient last visit(LVLS). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |