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Transthyretin-mediated AmyloidosisPhase 1NCT06527755

A Study to Assess the PK, PD, Safety and Tolerability of Eplontersen in Healthy Chinese Volunteers

A Phase 1 study testing Eplontersen Solution for Injection in people with Transthyretin-mediated Amyloidosis, run by AstraZeneca at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1 study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of eplontersen following single dosing in healthy Chinese participants. Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Transthyretin-mediated Amyloidosis
What is being tested?
Eplontersen Solution for Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteChina
Study dates
6 Aug 2024to 15 Nov 2024
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 60 years
  • All sexes
  • Healthy volunteers accepted
  • 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* Chinese males or females of non-childbearing potential, aged 18 to 60 inclusive at the time of informed consent.
  • Participants will be confirmed to be healthy according to the medical history, electrocardiogram (ECG), vital signs, laboratory results, and physical examination as determined by the Investigator.
  • Females must be non-pregnant and non-lactating, and either surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal (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*, or if engaged in sexual relations with a female of child-bearing potential, the participant must be using an highly effective contraceptive method from the time of signing the informed consent form until at least 24 weeks after study intervention administration.
  • Abstinence is only acceptable as true abstinence, ie, when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a study and withdrawal are not acceptable methods of contraception.
  • Willing to refrain from strenuous exercise/activity (eg, heavy lifting, weight training, intense aerobics classes) for at least 72 hours prior to study visits.
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  • Weight ≥ 50 kg and body mass index (BMI) of 19 to 30 kg/m2 at screening (including cutoff).
  • BMI = weight (kg)/height2 (m2).
  • Willingness to take vitamin A supplements (recommended daily allowance [RDA] of approximately 3000 IU/day until the last post-treatment follow-up visit [Day 92; 13 weeks after the dosing]).

Who cannot join

  • Clinically significant abnormalities in medical history (eg, major surgery within 6 months of screening, history or presence of hepatic, renal, hematological, endocrine, or cardiovascular disease) 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 ratio (UPCR) ≥ 200 mg/g. In the event of UPCR above this threshold ineligibility may be confirmed by a repeat random spot UPCR ≥ 200 mg/g or a 24-hour urine protein ≥ 200 mg/24 hour;
  • Positive test for blood (including trace) on urinalysis that is subsequently confirmed with urine microscopy showing > 5 red blood cells per high power field;
  • Alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, and blood urea > upper limit of normal (ULN);
  • Fasting blood glucose > ULN;
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  • Platelet count < lower limit of normal (LLN);
  • Estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) ≤ 60 mL/min/1.73m2.
  • Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Day 1.
  • Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
  • Known history of or positive test for human immunodeficiency virus (HIV), hepatitis B antigen, and hepatitis C antibody.
  • Uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg, or diastolic BP > 100 mmHg).
  • 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.
  • Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of study intervention, whichever is longer.
  • Previous treatment with an oligonucleotide (including small interfering ribonucleic acid) within 4 months of screening if single dose received, or within 12 months of screening if multiple doses received (exception for SARS-Cov2 vaccines [both mRNA and viral vector vaccines]; any vaccine should be administered at least 7 days prior to study intervention).
  • History of bleeding diathesis or coagulopathy.
  • Regular use of alcohol within 6 months prior to screening (> 7 drinks/wk for females, > 14 drinks/wk for males [1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor]), or use of soft drugs (such as marijuana) within 3 months prior to screening, or hard drugs (such as cocaine and phencyclidine) within 1 year prior to screening, or positive urine drug and alcohol screen at screening.
  • Concomitant medication restrictions including any prescription and over-the-counter (OTC) and herbal remedies, other than occasional acetaminophen (paracetamol) or ibuprofen unless authorized by the Study Clinical Lead.
  • Smoking limitations: smoking > 10 cigarettes a day.
  • Blood donation of 50 to 499 mL within 30 days of screening or of > 499 mL within 60 days of screening.
  • Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Research Site

    Beijing, 100029

Other trials in China

About this study

Official title: A Phase 1, Open-Label Study to Assess the Pharmacokinetics (PK), Pharmacodynamics (PD), Safety and Tolerability of Eplontersen Following Subcutaneous Administration of a Single Dose in Healthy Chinese Volunteers

This is a Phase 1 study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of eplontersen following single dosing in healthy Chinese participants. The objectives of the study are: to characterize the pharmacokinetic (PK) profiles and the pharmacodynamic (PD) profiles, and to evaluate the safety and tolerability and the immunogenicity of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participants.

Read the detailed description

This is a Phase 1, open-label, single-dose, single-arm study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of eplontersen following subcutaneous (SC) administration in healthy Chinese male and female participants. Approximately 12 healthy Chinese participants, aged 18 to 60 years, will be assigned to study intervention of a signle dose of eplontersen 45 mg following subcutaneous administration. Including the administration dosing day, the follow-up period is total of 92 days. The primary objective of this study is to characterize the PK profile of eplontersen, the PK parameters for eplontersen including, but not limited to: Cmax, tmax, t½λz, AUC0-24h, and AUC0-168h. The secondary objective of this study is to characterize the PD profiles of eplontersen, this includes the measures of change and percent change from baseline in serum TTR levels at specified timepoints. The safety objective of this study is to evaluate the safety and tolerability of eplontersen, this includes the measures of AEs/SAEs, vital signs, physical examinations, safety laboratory assessments and 12-lead ECG. Also the exploratory objective of this study is to evaluate the immunogenicity of eplontersen, this includes the measures of but not limited to anti-drug antibodies (ADA) prevalence and incidence, different ADA status at specified timepoints.

Being tested
Eplontersen Solution for Injection
Keywords
Eplontersen, PK, PD, Safety, Tolerability, Open Label, Single Dose

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Eplontersen Solution for InjectionDrug

    Also called Eplontersen

    an autoinjector with 0.8 mL deliverable volume (at 56 mg/mL concentration) will be provided, total dose is 45 mg.

Study groups in NCT06527755
Study groupRoleWhat they receive
EplontersenExperimentalSingle arm
Receives: Drug: Eplontersen Solution for Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PK parameters: Maximum Observed Concentration(Cmax)

    To characterize the pharmacokinetic (PK) profiles of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participants

    Measured: collect PK sample in pre-dose of Day 1 and 0.5 hours, 1 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours of post-dose, and in Day 8, Day 15, Day 29, Day 50, Day 71, Day 92

  2. PK parameters: Time to Maximal Concentration (tmax)

    To characterize the pharmacokinetic (PK) profiles of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participants

    Measured: collect PK sample in pre-dose of Day 1 and 0.5 hours, 1 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours of post-dose, and in Day 8, Day 15, Day 29, Day 50, Day 71, Day 92

  3. PK parameters: Plasma Half-life Associated with the Apparent Terminal Elimination Phase (t½λz)

    To characterize the pharmacokinetic (PK) profiles of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participants

    Measured: collect PK sample in pre-dose of Day 1 and 0.5 hours, 1 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours of post-dose, and in Day 8, Day 15, Day 29, Day 50, Day 71, Day 92

  4. PK parameters: Area Under Plasma Concentration-time Curve (0-24 hours) (AUC0-24h)

    To characterize the pharmacokinetic (PK) profiles of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participants

    Measured: collect PK sample in pre-dose of Day 1 and 0.5 hours, 1 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours of post-dose, and in Day 8, Day 15, Day 29, Day 50, Day 71, Day 92

  5. PK parameters: Area Under Plasma Concentration-time Curve (0-168 hours) (AUC0-168h)

    To characterize the pharmacokinetic (PK) profiles of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participants

    Measured: collect PK sample in pre-dose of Day 1 and 0.5 hours, 1 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours of post-dose, and in Day 8, Day 15, Day 29, Day 50, Day 71, Day 92

Secondary outcomes (1)

  1. The change and percent change from baseline in serum (Transthyretin) TTR levels at specified timepoints

    To characterize the pharmacodynamic (PD) profiles of eplontersen following subcutaneous administration of a single 45 mg dose in healthy Chinese participant

    Measured: collect PD sample in screening visit, pre-dose of Day 1 and Day 8, Day 15, Day 29, Day 50, Day 71, Day 92

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2024
  2. Study start6 Aug 2024
  3. Primary completion11 Sep 2024
  4. Study completion15 Nov 2024

Resources

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
Other
Allocation
Not applicable
Intervention model
Single group
Model description
This study is a single-arm study.
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06527755
Sponsor's protocol ID
D8450C00006
Status last verified
Nov 2024
First submitted
9 Jul 2024
Last updated
21 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual subject-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/ AZ accept request for IPD, but this does not mean all requests will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Eplontersen Solution for Injection in people with Transthyretin-mediated Amyloidosis, run by AstraZeneca at 1 site in China.

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 9 inclusion and 21 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 21 Nov 2024. 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 China. 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. 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?

PK parameters: Maximum Observed Concentration(Cmax) (time frame: collect PK sample in pre-dose of Day 1 and 0.5 hours, 1 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours of post-dose, and in Day 8, Day 15, Day 29, Day 50, Day 71, Day 92). The study lists 5 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 NCT06527755.

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 21 Nov 2024.

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