Healthy ParticipantsPhase 1NCT04302064
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending and Multiple Doses of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Healthy Japanese Participants
A Phase 1 study testing Eplontersen in people with Healthy Participants, run by Ionis Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
To evaluate the safety and tolerability of single and potentially multiple doses of Eplontersen administered subcutaneously (SC) to healthy Japanese participants. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- Eplontersen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2020to 10 Sep 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 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
- Healthy Japanese males or females of non-childbearing potential, aged 20 to 65 inclusive at the time of informed consent defined as being of first- or second-generation ethnic origin with each set of parents qualifying as Japanese under the prior generation. Generations will be defined as follows:
- First generation Japanese participants must be born in Japan, cannot have lived outside of Japan for more than 10 years, must maintain Japanese diet, culture and lifestyle and parents and both sets of grandparents are of Japanese origin
- Second-generation Japanese are participants who are born outside of Japan to the first-generation Japanese parents
- Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal (defined as 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory involved Males must be surgically sterile or abstinent*, if engaged in sexual relations with a female of child-bearing potential, the participant must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 91 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug (Eplontersen or placebo)
- Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.
- Willingness to take vitamin A supplements
Who cannot join
- Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening) or physical examination
- Screening laboratory results as follows, or any other clinically significant abnormalities in Screening laboratory values that would render a participant unsuitable for inclusion
- Random spot urine protein/creatinine (P/C) ratio (UPCR) ≥ 200 milligrams per gram (mg/g).
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) > upper limit of normal (ULN)
- Fasting blood glucose > ULN
- Platelet count < lower limit of normal (LLN)
- Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm Hg])
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blinded, Placebo-Controlled, Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending and Multiple Doses of ION-682884 in Healthy Japanese Participants
To evaluate the safety and tolerability of single and potentially multiple doses of Eplontersen administered subcutaneously (SC) to healthy Japanese participants.
Read the detailed description
This is a single-center, double-blinded, placebo-controlled study in up to 44 participants. Participants will be randomized to receive three subcutaneous single-ascending doses and potentially multiple doses of Eplontersen or placebo.
- Conditions
- Healthy Participants
- Being tested
- Eplontersen, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplontersenDrug
Also called ION-682884, AKCEA-TTR-LRx, IONIS-TTR-LRx
Eplontersen administered SC
PlaceboDrug
Eplontersen-matching placebo administered SC
| Study group | Role | What they receive |
|---|---|---|
| Eplontersen | Experimental | Single dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen administered SC. Receives: Drug: Eplontersen |
| Placebo | Placebo comparator | Single dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen-matching placebo administered SC. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
Measured: Up to 92 days
Percentage of Participants with TEAEs Potentially Related to Study Drug
Measured: Up to 92 days
Percentage of Participants with Changes in Clinically Significant (CS) Laboratory Value Abnormalities
Measured: Up to 92 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2020
- Study start23 Apr 2020
- Primary completion10 Sep 2020
- Study completion10 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 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
- NCT04302064
- Sponsor's protocol ID
- ION-682884-CS20
- Status last verified
- Mar 2022
- First submitted
- 6 Mar 2020
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Diep JK, Yu RZ, Viney NJ, Schneider E, Guo S, Henry S, Monia B, Geary R, Wang Y. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Dec;88(12):5389-5398. doi: 10.1111/bcp.15468. Epub 2022 Aug 7.
PubMed 35869634
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded, Placebo-Controlled, Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending and Multiple Doses of ION-682884 in Healthy Japanese Participants
- ClinicalTrials.gov ID
- NCT04302064
- Acronym / sponsor ID
- ION-682884-CS20
- Conditions
- Healthy Participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Apr 2020 (actual)
- Primary completion
- 10 Sep 2020 (actual)
- Study completion
- 10 Sep 2020 (actual)
- First posted
- 10 Mar 2020 (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 of single and potentially multiple doses of Eplontersen administered subcutaneously (SC) to healthy Japanese participants.
Detailed description
This is a single-center, double-blinded, placebo-controlled study in up to 44 participants. Participants will be randomized to receive three subcutaneous single-ascending doses and potentially multiple doses of Eplontersen or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eplontersen | Experimental | Drug: EplontersenSingle dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen administered SC. |
| Placebo | Placebo comparator | Drug: PlaceboSingle dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen-matching placebo administered SC. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
- Healthy Japanese males or females of non-childbearing potential, aged 20 to 65 inclusive at the time of informed consent defined as being of first- or second-generation ethnic origin with each set of parents qualifying as Japanese under the prior generation. Generations will be defined as follows:
- Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal (defined as 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory involved Males must be surgically sterile or abstinent*, if engaged in sexual relations with a female of child-bearing potential, the participant must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 91 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug (Eplontersen or placebo)
- Willingness to take vitamin A supplements
Key exclusion criteria (8 listed)
- Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening) or physical examination
- Screening laboratory results as follows, or any other clinically significant abnormalities in Screening laboratory values that would render a participant unsuitable for inclusion
- Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm Hg])
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
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 |
|---|---|---|
| EplontersenAlso: ION-682884, AKCEA-TTR-LRx, IONIS-TTR-LRxEplontersen administered SC | Drug | Eplontersen |
| PlaceboEplontersen-matching placebo administered SC | Drug | Placebo |
Primary outcome
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
Time frame: Up to 92 days
Percentage of Participants with TEAEs Potentially Related to Study Drug
Time frame: Up to 92 days
Percentage of Participants with Changes in Clinically Significant (CS) Laboratory Value Abnormalities
Time frame: Up to 92 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 31 Mar 2022.
- Derived from this study: PubMed 35869634Diep JK, Yu RZ, Viney NJ, Schneider E, Guo S, Henry S, Monia B, Geary R, Wang Y. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Dec;88(12):5389-5398. doi: 10.1111/bcp.15468. Epub 2022 Aug 7.
- Individual participant dataSharing planned: No
Related trials for Healthy Participants
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
RecruitingPhase 1
A Study to Evaluate the Metabolism, the Routes and Extent of Elimination, and Drug Levels of [14C]Navlimetostat (BMS-986504) in Healthy Female Participants
Healthy Female Participants
Not yet recruiting
REM Enhancement Sleep Technology for Well-being, Emotion, and Life Lift
Healthy Adult Participants
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 Eplontersen in people with Healthy Participants, run by Ionis Pharmaceuticals, Inc. at 1 site in United States.
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 7 inclusion and 8 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 31 Mar 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 United States. 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?
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity (time frame: Up to 92 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04302064, which also lists 1 linked publication.
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 31 Mar 2022.