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

NCT03647228 | Completed Phase 1 FDA Drug

• 2 other identifiers: ION-827359-CS12018-002621-27
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 8

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.

Conditions

Healthy Subjects; Cystic Fibrosis

Keywords

ION-827359; ENaC

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event

  Up to 113 Days

Secondary Outcomes (6)

• Cmax: maximum observed drug concentration in plasma of IONIS-ENaCRx

  Up to 113 Days

• Tmax: time taken to reach maximal concentration in plasma 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

• CL/F: apparent total clearance of IONIS-ENaCRx

  Up to 113 Days

• t1/2λz: termination half-life of IONIS-ENaCRx

  Up to 113 Days

Study Arms (2)

IONIS-ENaCRx

EXPERIMENTAL

Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.

Drug: IONIS-ENaCRx

Placebo

PLACEBO COMPARATOR

Placebo comparator calculated volume to match active comparator inhaled or nebulized.

Drug: Placebo

Interventions

IONIS-ENaCRx DRUG

Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.

IONIS-ENaCRx

Placebo DRUG

Placebo comparator calculated volume to match active comparator inhaled or nebulized.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.
• Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
• Willing to refrain from strenuous exercise/activity for at least 72 hours prior to study visits
• Body mass index (BMI) \< 35 kg/m2 with a minimum weight of 45 kg
• Normal diffusing capacity in the lung (≥ 80% predicted) at Screening

You may not qualify if:

• Urine protein/creatinine (P/C) ratio ≥ 0.2 mg/mg
• Positive test (including trace) for blood on urinalysis
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN), fasting blood glucose, potassium \> upper limit of normal (ULN)
• Platelet count \< LLN
• Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
• Respiratory infection within 4 weeks of Study Day 1
• Presence or past history of CS chronic respiratory disease, including any current history (or within 2 years) of asthma. History of allergic rhinitis is acceptable
• Forced expiratory volume in 1 second (FEV1) \< 80% of predicted at Screening or an FEV1/FVC ratio of \< 0.7
• Smoking of a tobacco or nicotine-containing product within the previous 6 months (use of a nicotine patch is permitted) or a smoking history of ≥ 10 pack years
• Any CS finding on chest radiograph
• Uncontrolled hypertension (blood pressure \[BP\] \> 160/100 mm Hg) at Screening
• Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer
• Any history of previous treatment with an oligonucleotide
• Regular use of alcohol within 6 months prior to screening or hard drugs within 1 year prior to screening, or positive urine drug screen at Screening
• Blood donation of 50 to 499 mL within 30 days of screening or of \> 499 mL within 60 days of screening

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (8)

Universitätsmedizin Essen

Essen, 45239, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, D-60589, Germany

Location

Lungenheilkunde München-Pasing

München, 81241, Germany

Location

Medicines Evaluation Unit

Wythenshawe, Manchester, M23 9QZ, United Kingdom

Location

Celerion

Belfast, Northern Ireland, BT9 6AD, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Adults Cystic Fibrosis King's College Hospital - Hambleden Wing (East)

London, SE5 9RS, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 27, 2018
• Study Start: December 13, 2018
• Primary Completion: October 13, 2020
• Study Completion: October 13, 2020
• Last Updated: February 4, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); GB (5)