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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-13

Study Completion Date

2020-10-13

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Healthy Subjects Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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IONIS-ENaCRx

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

Group Type EXPERIMENTAL

IONIS-ENaCRx

Intervention Type DRUG

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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IONIS-ENaCRx

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.
2. 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
3. Willing to refrain from strenuous exercise/activity for at least 72 hours prior to study visits
4. Body mass index (BMI) \< 35 kg/m2 with a minimum weight of 45 kg
5. Normal diffusing capacity in the lung (≥ 80% predicted) at Screening

1. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.
2. 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
3. Confirmed diagnosis of CF by seat chloride and/or genetics by referring clinician
4. FEV1 \>/= 50% of predicted
5. Stable CF disease as judged by the Investigator
6. Weight \> 40 kg

Exclusion Criteria

1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to:

1. Urine protein/creatinine (P/C) ratio ≥ 0.2 mg/mg
2. Positive test (including trace) for blood on urinalysis
3. 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)
4. Platelet count \< LLN
2. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
3. Respiratory infection within 4 weeks of Study Day 1
4. 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
5. Forced expiratory volume in 1 second (FEV1) \< 80% of predicted at Screening or an FEV1/FVC ratio of \< 0.7
6. 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
7. Any CS finding on chest radiograph
8. Uncontrolled hypertension (blood pressure \[BP\] \> 160/100 mm Hg) at Screening
9. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer
10. Any history of previous treatment with an oligonucleotide
11. 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
12. Blood donation of 50 to 499 mL within 30 days of screening or of \> 499 mL within 60 days of screening

1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to:

1. Abnormal liver function defined as \> 2 times upper limit of normal (ULN) for bilirubin, or 3 time ULN for ALT, AST, or alkaline phosphatase
2. Platelet count \< LLN
2. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
3. Respiratory infection within 4 weeks of Study Day 1
4. Colonization with Burkholderia cepacia or M. abscessus

Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes