Healthy SubjectsPhase 1NCT03647228
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
A Phase 1 study testing IONIS-ENaCRx in people with Healthy Subjects and Cystic Fibrosis, run by Ionis Pharmaceuticals, Inc. at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects, Cystic Fibrosis
- What is being tested?
- IONIS-ENaCRx
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 13 Dec 2018to 13 Oct 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.
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- 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
- Confirmed diagnosis of CF by seat chloride and/or genetics by referring clinician
- FEV1 >/= 50% of predicted
- Stable CF disease as judged by the Investigator
- Weight > 40 kg
Who cannot join
- 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:
- 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
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- 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
- 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:
- Abnormal liver function defined as > 2 times upper limit of normal (ULN) for bilirubin, or 3 time ULN for ALT, AST, or alkaline phosphatase
- 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
- Colonization with Burkholderia cepacia or M. abscessus
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United Kingdom5 sites
Celerion
Belfast, Northern Ireland, BT9 6AD
Western General Hospital
Edinburgh, EH4 2XU
Adults Cystic Fibrosis King's College Hospital - Hambleden Wing (East)
London, SE5 9RS
Royal Brompton Hospital
London, SW3 6HP
Medicines Evaluation Unit
Wythenshawe, Manchester, M23 9QZ
Germany3 sites
Universitätsmedizin Essen
Essen, 45239
Universitätsklinikum Frankfurt
Frankfurt, D-60589
Lungenheilkunde München-Pasing
München, 81241
About this study
Official title: A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients With Cystic Fibrosis
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.
Read the 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.
- Conditions
- Healthy Subjects, Cystic Fibrosis
- Being tested
- IONIS-ENaCRx, Placebo
- Keywords
- ION-827359, ENaC
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IONIS-ENaCRxDrug
Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.
PlaceboDrug
Placebo comparator calculated volume to match active comparator inhaled or nebulized.
| Study group | Role | What they receive |
|---|---|---|
| IONIS-ENaCRx | Experimental | Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized. Receives: Drug: IONIS-ENaCRx |
| Placebo | Placebo comparator | Placebo comparator calculated volume to match active comparator inhaled or nebulized. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event
Measured: Up to 113 Days
Secondary outcomes (6)
Cmax: maximum observed drug concentration in plasma of IONIS-ENaCRx
Measured: Up to 113 Days
Tmax: time taken to reach maximal concentration in plasma of IONIS-ENaCRx
Measured: Up to 113 Days
AUCt: area under the plasma concentration-time curve from time zero to time t for IONIS-ENaCRx
Measured: Up to 113 Days
CL/F: apparent total clearance of IONIS-ENaCRx
Measured: Up to 113 Days
t1/2λz: termination half-life of IONIS-ENaCRx
Measured: Up to 113 Days
The amount of administered dose of IONIS-ENaCRx excreted in urine over a 24-hour period
Measured: Up to 113 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2018
- Study start13 Dec 2018
- Primary completion13 Oct 2020
- Study completion13 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03647228
- Sponsor's protocol ID
- ION-827359-CS1
- Other IDs
- 2018-002621-27, 2018
- Status last verified
- Feb 2021
- First submitted
- 23 Aug 2018
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT03647228
- Acronym / sponsor ID
- ION-827359-CS1
- Conditions
- Healthy Subjects, Cystic Fibrosis
- Keywords
- ION-827359, ENaC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Dec 2018 (actual)
- Primary completion
- 13 Oct 2020 (actual)
- Study completion
- 13 Oct 2020 (actual)
- First posted
- 27 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IONIS-ENaCRx | Experimental | Drug: IONIS-ENaCRxAscending single and multiple doses of IONIS-ENaCRx inhaled or nebulized. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo comparator calculated volume to match active comparator inhaled or nebulized. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (22 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IONIS-ENaCRxAscending single and multiple doses of IONIS-ENaCRx inhaled or nebulized. | Drug | IONIS-ENaCRx |
| PlaceboPlacebo comparator calculated volume to match active comparator inhaled or nebulized. | Drug | Placebo |
Primary outcome
Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event
Time frame: Up to 113 Days
6 secondary outcomes
Cmax: maximum observed drug concentration in plasma of IONIS-ENaCRx
Time frame: Up to 113 Days
Tmax: time taken to reach maximal concentration in plasma of IONIS-ENaCRx
Time frame: Up to 113 Days
AUCt: area under the plasma concentration-time curve from time zero to time t for IONIS-ENaCRx
Time frame: Up to 113 Days
CL/F: apparent total clearance of IONIS-ENaCRx
Time frame: Up to 113 Days
t1/2λz: termination half-life of IONIS-ENaCRx
Time frame: Up to 113 Days
The amount of administered dose of IONIS-ENaCRx excreted in urine over a 24-hour period
Time frame: Up to 113 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IONIS-ENaCRx in people with Healthy Subjects and Cystic Fibrosis, run by Ionis Pharmaceuticals, Inc. at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event (time frame: Up to 113 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.