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

NCT06527755 | Completed Phase 1 FDA Drug

• 1 other identifier: D8450C00006
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Transthyretin-mediated Amyloidosis

Keywords

Eplontersen; PK; PD; Safety; Tolerability; Open Label; Single Dose

Outcome Measures

Primary Outcomes (5)

• 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

  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

  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

  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

  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

  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

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

Study Arms (1)

Eplontersen

EXPERIMENTAL

Single arm

Drug: Eplontersen Solution for Injection

Interventions

Eplontersen Solution for Injection DRUG

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

Also known as: Eplontersen

Eplontersen

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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 \[Day 92; 13 weeks after the dosing\]).

You may not qualify if:

• 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.
• 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;
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Beijing, 100029, China

Location

MeSH Terms

Interventions

Injections; eplontersen

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yang Lin, Medical PhD

  Beijing Anzhen Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a single-arm study.

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 30, 2024
• Study Start: August 6, 2024
• Primary Completion: September 11, 2024
• Study Completion: November 15, 2024
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/.
• Access Criteria: When a request has been approved, AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statement at: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/.

Locations

CN (1)