A Phase 1/2 Multicenter, First-in-human, Ascending Dose Trial Evaluating the Safety, Tolerability, and Efficacy of a Lipid Nanoparticle Formulation of CRISPR-Guide RNA-Cas9 Nuclease (CTX340) for In Vivo Editing of the Angiotensinogen (AGT) Gene in Participants With Hypertension
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- CRISPR Therapeutics AG
- Enrollment
- 69
- Locations
- 2
- Primary Endpoint
- Phase 1: Incidence of dose-limiting toxicities (DLTs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- 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)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age: ≥18 and ≤75 years.
- •Body mass index ≤40 kg/m
- •24-hour mean ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP) measurement of ≥130 mm Hg but ≤160 mm Hg despite treatment
- •Be on treatment with ≥4 antihypertensive therapies at effective doses, of which ≥1 must be a diuretic.
- •Participants who at any point had childbearing potential must currently be postmenopausal
- •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
- •Serum aldosterone and direct renin concentration (or plasma renin activity [PRA]) suggestive of primary aldosteronism
- •Mean diastolic blood pressure (DBP) ≤65 mm Hg on screening ABPM.
- •Participants with vascular cause of hypertension which may be amendable to revascularization
- •Participants with treatable/reversible causes of uncontrolled hypertension
- •History of renal artery denervation within past 12 months.
- •Orthostatic hypotension
- •Complete blood count (CBC) outside the specified ranges per protocol.
- •Evidence of liver disease
- •History of a significant coagulation disorder.
- •Uncontrolled or untreated thyroid disease
Arms & Interventions
Phase 1: CTX340
Phase 1 is An Open-Label, Ascending Dose Design.
Intervention: CTX340 (Drug)
Phase 2: Placebo
Phase 2: Placebo.
Intervention: Placebo (Drug)
Phase 2: Recommended Phase 2 Dose CTX340
Phase 2: Recommended Phase 2 Dose CTX340.
Intervention: CTX340 (Drug)
Outcomes
Primary Outcomes
Phase 1: Incidence of dose-limiting toxicities (DLTs)
Time Frame: 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
Time Frame: Through 6 months of follow-up.
To evaluate the pharmacodynamics (PD) effect of CTX340 at the recommended Phase 2 dose (RP2D)
Secondary Outcomes
- To assess the safety of CTX340(From CTX340 infusion up to 12 months)
- To assess the effect of CTX340 on systolic blood pressure (SBP) by ambulatory blood pressure monitoring (ABPM)(From CTX340 infusion up to 12 months)
- To assess the pharmacodynamics (PD) effect of CTX340(Over 12 months, compared to baseline)
- To characterize the pharmacokinetics (PK) of CTX340(From CTX340 infusion up to 12 months)