Hypertension
Conditions
Brief summary
A Study of CTX340 in Participants with Uncontrolled Hypertension.
Detailed description
This is a dose ascending study of CTX340 in participants with hypertension. Subjects will receive CTX340 or placebo via intravenous (IV) infusion.
Interventions
DRUGCTX340
CTX340 is an in vivo gene editing therapy designed to utilize clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) to target and disrupt human angiotensinogen (AGT) gene in liver.
DRUGPlacebo
One of the arms in Phase 2 will be placebo.
Sponsors
CRISPR Therapeutics AG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Phase 1 is Open-Label, while Phase 2 is Double-Blind (Participant, Investigator)
Intervention model description
Phase 1: Sequential Single Ascending Dose Escalation Phase 2: Placebo Controlled Parallel Group
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Age: ≥18 and ≤75 years. 2. Body mass index ≤40 kg/m2. 3. 24-hour mean ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP) measurement of ≥130 mm Hg but ≤160 mm Hg despite treatment 4. Be on treatment with ≥4 antihypertensive therapies at effective doses, of which ≥1 must be a diuretic. 5. Participants who at any point had childbearing potential must currently be postmenopausal 6. All participants capable of producing sperm must agree to the use of an acceptable method of effective contraception and their partners with childbearing potential should also agree to use an effective method of contraception.
Exclusion criteria
1. Serum aldosterone and direct renin concentration (or plasma renin activity \[PRA\]) suggestive of primary aldosteronism 2. Mean diastolic blood pressure (DBP) ≤65 mm Hg on screening ABPM. 3. Participants with vascular cause of hypertension which may be amendable to revascularization 4. Participants with treatable/reversible causes of uncontrolled hypertension 5. History of renal artery denervation within past 12 months. 6. Orthostatic hypotension 7. Complete blood count (CBC) outside the specified ranges per protocol. 8. Evidence of liver disease 9. History of a significant coagulation disorder. 10. Uncontrolled or untreated thyroid disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Incidence of dose-limiting toxicities (DLTs) | Up to 12 months | To evaluate the safety and tolerability of a single ascending dose of CTX340 in participants with hypertension to determine the recommended Phase 2 dose (RP2D). |
| Phase 2: Percentage change in circulating angiotensinogen (AGT) concentration from baseline | Through 6 months of follow-up. | To evaluate the pharmacodynamics (PD) effect of CTX340 at the recommended Phase 2 dose (RP2D) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the safety of CTX340 | From CTX340 infusion up to 12 months | Incidence of adverse events (AEs), including treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs), clinically significant laboratory abnormalities, and clinically significant abnormal vital signs during 12 months of follow-up. |
| To assess the effect of CTX340 on systolic blood pressure (SBP) by ambulatory blood pressure monitoring (ABPM) | From CTX340 infusion up to 12 months | Change from baseline in systolic blood pressure (SBP) assessed by 24-hour ambulatory blood pressure monitoring (ABPM) |
| To assess the pharmacodynamics (PD) effect of CTX340 | Over 12 months, compared to baseline | Percentage change in circulating angiotensinogen (AGT) concentrations over time compared to baseline. |
| To characterize the pharmacokinetics (PK) of CTX340 | From CTX340 infusion up to 12 months | Plasma levels of LNP (ionizable lipid and PEG lipid) |
Countries
Australia, United States
Contacts
CONTACTClinical Trials
Outcome results
None listed