Healthy ParticipantsPhase 1NCT03582462
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of IONIS FXI-LRx in up to 84 Healthy Volunteers
A Phase 1 study testing IONIS FXI-LRx in people with Healthy Participants, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.
Trial summary
To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics, including Factor XI activity and antigen levels, activated partial thromboplastin time, prothrombin time and international normalized ratio of single and multiple doses of Factor XI antisense inhibitor administered subcutaneously to… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- IONIS FXI-LRx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteCanada
- Study dates
- 9 Jul 2018to 26 Apr 2019
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) ≤ 35 kg/m2
- Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
- Males must be surgically sterile, abstinent or, if engaged in sexual relations with a female of child-bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug
- Willing to refrain from strenuous exercise/activity for at least 72 hrs prior to study visits
- Must abstain from alcoholic beverages for at least 48 hrs prior to clinic visits and not increase alcohol consumption during the study
Who cannot join
- Clinically-significant abnormalities in medical history, screening laboratory results, physical examination that would render a subject unsuitable for inclusion. Including but not limited to:
- Platelet count < LLN
- INR > 1.4
- aPTT > ULN
- FXI activity < 0.7 U/mL
- Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
Show all 9Show fewer
- Any history of previous treatment with an oligonucleotide
- History of bleeding diathesis or coagulopathy
- Uncontrolled hypertension (BP > 160/100 mm Hg)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ION-957943 (IONIS FXI-LRX, a GalNAc Conjugated 2'-MOE Chimeric Antisense Oligonucleotide Inhibitor of Factor XI) Administered Subcutaneously to Healthy Volunteers
To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics, including Factor XI activity and antigen levels, activated partial thromboplastin time, prothrombin time and international normalized ratio of single and multiple doses of Factor XI antisense inhibitor administered subcutaneously to healthy volunteers.
Read the detailed description
This will be a Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study conducted at a single center. The study consists of 4 escalating single-dose cohorts (n = 8 per cohort, randomized 3 IONIS FXI-LRx active:1 placebo), 3 escalating multiple-dose cohorts with weekly Study Drug (IONIS FXI-LRx or placebo) administration for 8 healthy volunteers per cohort, randomized 3 active:1 placebo, and 1 multiple-dose cohort of 10 healthy volunteers randomized 3 active:2 placebo with Study Drug administration every 4 weeks.
Approximately 66 healthy volunteers are planned to be enrolled in this study. Additional healthy volunteers may be added to better assess the safety, tolerability or pharmacokinetic profile of IONIS FXI-LRx to meet study objectives.
- Conditions
- Healthy Participants
- Being tested
- IONIS FXI-LRx, Placebo
- Keywords
- IONIS FXI-L, Factor XI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IONIS FXI-LRxDrug
Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection
PlaceboDrug
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| IONIS FXI-LRx | Experimental | Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection. Receives: Drug: IONIS FXI-LRx |
| Placebo | Placebo comparator | Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator. 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 Treatment-Emergent Adverse Events
Measured: Up to 232 Days
Secondary outcomes (3)
Cmax: maximum observed drug concentration in plasma of IONIS FXI-LRx
Measured: Up to 232 Days
Tmax: time taken to reach maximal concentration in plasma of IONIS FXI-LRx
Measured: Up to 232 Days
AUC: area under the plasma concentration time curve for IONIS FXI-LRx
Measured: Up to 232 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start9 Jul 2018
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ParticipantsStudies 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
- 66 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
- NCT03582462
- Sponsor's protocol ID
- ION 957943-CS1
- Status last verified
- Jan 2022
- First submitted
- 13 Jun 2018
- Last updated
- 18 Jan 2022
- 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 18 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ION-957943 (IONIS FXI-LRX, a GalNAc Conjugated 2'-MOE Chimeric Antisense Oligonucleotide Inhibitor of Factor XI) Administered Subcutaneously to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03582462
- Acronym / sponsor ID
- ION 957943-CS1
- Conditions
- Healthy Participants
- Keywords
- IONIS FXI-L, Factor XI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Jul 2018 (actual)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 11 Jul 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.
To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics, including Factor XI activity and antigen levels, activated partial thromboplastin time, prothrombin time and international normalized ratio of single and multiple doses of Factor XI antisense inhibitor administered subcutaneously to healthy volunteers.
Detailed description
This will be a Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study conducted at a single center. The study consists of 4 escalating single-dose cohorts (n = 8 per cohort, randomized 3 IONIS FXI-LRx active:1 placebo), 3 escalating multiple-dose cohorts with weekly Study Drug (IONIS FXI-LRx or placebo) administration for 8 healthy volunteers per cohort, randomized 3 active:1 placebo, and 1 multiple-dose cohort of 10 healthy volunteers randomized 3 active:2 placebo with Study Drug administration every 4 weeks.
Approximately 66 healthy volunteers are planned to be enrolled in this study. Additional healthy volunteers may be added to better assess the safety, tolerability or pharmacokinetic profile of IONIS FXI-LRx to meet study objectives.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IONIS FXI-LRx | Experimental | Drug: IONIS FXI-LRxAscending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection. |
| Placebo | Placebo comparator | Drug: PlaceboSterile Normal Saline (0.9% NaCl) calculated volume to match active comparator. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Body mass index (BMI) ≤ 35 kg/m2
- Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
- Males must be surgically sterile, abstinent or, if engaged in sexual relations with a female of child-bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug
- Willing to refrain from strenuous exercise/activity for at least 72 hrs prior to study visits
- Must abstain from alcoholic beverages for at least 48 hrs prior to clinic visits and not increase alcohol consumption during the study
Key exclusion criteria (9 listed)
- Clinically-significant abnormalities in medical history, screening laboratory results, physical examination that would render a subject unsuitable for inclusion. Including but not limited to:
- Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
- Any history of previous treatment with an oligonucleotide
- History of bleeding diathesis or coagulopathy
- Uncontrolled hypertension (BP > 160/100 mm Hg)
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 FXI-LRxAscending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection | Drug | IONIS FXI-LRx |
| PlaceboSterile Normal Saline (0.9% NaCl) calculated volume to match active comparator | Drug | Placebo |
Primary outcome
Safety and Tolerability as Measured by the Number of Participants with Treatment-Emergent Adverse Events
Time frame: Up to 232 Days
3 secondary outcomes
Cmax: maximum observed drug concentration in plasma of IONIS FXI-LRx
Time frame: Up to 232 Days
Tmax: time taken to reach maximal concentration in plasma of IONIS FXI-LRx
Time frame: Up to 232 Days
AUC: area under the plasma concentration time curve for IONIS FXI-LRx
Time frame: Up to 232 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 18 Jan 2022.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IONIS FXI-LRx in people with Healthy Participants, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.
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 5 inclusion and 9 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 18 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 Treatment-Emergent Adverse Events (time frame: Up to 232 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 18 Jan 2022.