A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis

Phase 1

Completed

• Conditions: Healthy Subjects; Cystic Fibrosis
• Interventions: Drug: Placebo; Drug: IONIS-ENaCRx

• Registration Number: NCT03647228
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

This Phase 1/2a study is a double-blinded (subject and Investigator), randomized, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple nebulized doses of IONIS-ENaCRx.

Detailed Description

This study will be conducted in 3 parts: a single ascending dose (SAD) leading to a multiple ascending dose (MAD) in healthy volunteers, followed by a MAD in patients with cystic fibrosis. The study will enroll up to 88 participants.

The study will consist of 4 single-dose randomized cohorts. Participants enrolled will receive a single inhaled dose of the Study Drug (IONIS-ENaCRx or placebo) on Day 1.

Study Timeline

• Study First Submitted: 2018-08-23
• Study First Submitted QC: 2018-08-23
• Study First Posted: 2018-08-27
• Study Start: 2018-12-13
• Primary Completion: 2020-10-13
• Study Completion: 2020-10-13
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-02
• Last Update Posted: 2021-02-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo comparator calculated volume to match active comparator inhaled or nebulized.
IONIS-ENaCRx	IONIS-ENaCRx	Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event	Up to 113 Days

Secondary Outcome Measures

Name	Time	Method
Tmax: time taken to reach maximal concentration in plasma of IONIS-ENaCRx	Up to 113 Days
CL/F: apparent total clearance of IONIS-ENaCRx	Up to 113 Days
Cmax: maximum observed drug concentration in plasma of IONIS-ENaCRx	Up to 113 Days
t1/2λz: termination half-life of IONIS-ENaCRx	Up to 113 Days
AUCt: area under the plasma concentration-time curve from time zero to time t for IONIS-ENaCRx	Up to 113 Days
The amount of administered dose of IONIS-ENaCRx excreted in urine over a 24-hour period	Up to 113 Days

Trial Locations

Locations (8)

Universitätsmedizin Essen; 🇩🇪 Essen, Germany

Lungenheilkunde München-Pasing; 🇩🇪 München, Germany

Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Medicines Evaluation Unit; 🇬🇧 Wythenshawe, Manchester, United Kingdom

Adults Cystic Fibrosis King's College Hospital - Hambleden Wing (East); 🇬🇧 London, United Kingdom

Celerion; 🇬🇧 Belfast, Northern Ireland, United Kingdom

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Royal Brompton Hospital; 🇬🇧 London, United Kingdom