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.
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
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.
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.
- Conditions
- Transthyretin-mediated Amyloidosis
- 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 group | Role | What they receive |
|---|---|---|
| Eplontersen | Experimental | Single arm Receives: Drug: Eplontersen Solution for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
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
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
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)
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.
- First posted30 Jul 2024
- Study start6 Aug 2024
- Primary completion11 Sep 2024
- Study completion15 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin-mediated AmyloidosisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- 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)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yang Lin, Medical PhD, Principal investigator, Beijing Anzhen Hospital
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.