Single-dose efimosfermin alfa safety and drug-handling in healthy Chinese, Japanese, and White adults

A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Efimosfermin Alfa Administered as a Single Dose to Healthy Participants of Chinese, Japanese, and White/European Ancestry

We will test one single dose of efimosfermin alfa versus placebo in healthy Chinese, Japanese, and White/European adults to see if it is safe, how the body processes it, and whether it triggers immune responses.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: GlaxoSmithKline (Industry-sponsored)
• Locations: 1 site (Auckland)
• Trial ID: NCT07335198 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, first-time-in-Asia, single-dose study of efimosfermin alfa with a placebo comparator in healthy volunteers of Chinese, Japanese, and White/European ancestry. The study will collect safety and tolerability data, measure pharmacokinetics (how the drug is absorbed, distributed, metabolized, and eliminated), and evaluate immunogenicity (immune responses against the drug). Participants must meet defined weight and BMI limits and specific ancestry and residency criteria for each group. The study is sponsored by GlaxoSmithKline and conducted at a GSK investigational site in Auckland.

Who should consider this trial

Good fit: Healthy adults of Chinese, Japanese, or White/European ancestry who meet the study's weight, BMI, and ancestry/residency definitions are the intended participants.

Not a fit: People with active liver disease, major medical conditions, or who do not meet the specified ancestry/residency requirements — and anyone seeking direct therapeutic benefit — are unlikely to receive clinical benefit from this safety-focused study.

Why it matters

Potential benefit: If successful, this study could enable further development of efimosfermin alfa as a potential treatment for non-alcoholic fatty liver disease by establishing safe dosing and pharmacokinetics across Asian and White populations.

How similar studies have performed: Early-phase work with efimosfermin alfa and related compounds has produced preliminary safety and PK signals, but larger efficacy studies in NAFLD are still required.

Eligibility criteria

Inclusion Criteria:

Participants who are generally healthy as determined by medical evaluation

* Body weight at least 50.0 Kilogram (kg) for male participants or at least 45.0 kg for female participants
* Body mass index (BMI) within the range of 18.0 to 28.0 kilograms per square meter (kg/m\^2) (inclusive)
* Male and female participants
* Participants of Chinese ancestry are eligible if born in mainland China, Hong Kong, or Taiwan, and have lived outside China, Hong Kong, or Taiwan for less than 10 years at the time of screening.
* Participants of Japanese ancestry are eligible if born in Japan and Descendant of 2 ethnic Japanese parents and 4 ethnic Japanese grandparents; and. have lived outside Japan for less than 10 years at the time of screening.
* Participants of White/European ancestry are eligible if self-identified as being of White/European ancestry, (i.e., from the original peoples of Europe) irrespective of current place of residence; and.
* Descendant of 2 parents and 4 grandparents of White/European ancestry (that is \[i.e.\], from the original peoples of Europe) irrespective of place of birth or current place of residence.

Exclusion Criteria:

* History or presence of disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
* Current or chronic history of liver or biliary disease with the exception of Gilbert's syndrome or asymptomatic gallstones.
* History of pancreatic injury, pancreatitis or other pancreatic disease; history of Type one Diabetes Mellitus (T1DM) or positive glutamic acid decarboxylase auto-antibodies, or major Type two Diabetes Mellitus (T2DM) complications including severe gastroparesis and autonomic neuropathy.
* Abnormal blood pressure (defined as systolic Blood Pressure (BP) more than equal (\>=)140 millimeters of mercury (mmHg) or diastolic BP \>=90 mmHg) measured based on the average of triplicate BP readings).
* History of metabolic bone disorders including osteoporosis, osteopenia, or osteomalacia.
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
* Alanine transaminase (ALT) more than (\>)1.5 \* upper limit of normal (ULN).
* Total bilirubin \>1.5 \* ULN
* Known bleeding disorder.
* History of immunodeficiency diseases, including a positive test result for human immunodeficiency virus (HIV).
* Corrected QT Interval using Fridericia's Formula. (QTcF) \>=450 millisecond (msec)(male) or \>=470 msec (female) at Screening Visit based on the average of triplicate ECGs.
* Use of statins, other lipid lowering medications or hypertension medications unless on a stable dose for at least 3 months.
* Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever was longer; or longer if required by local regulations.
* Participants who have received native FGF21 or a FGF21 analog at any time in the past.
* Intended use of over the counter (OTC) or prescription medication (including herbal medications) within 7 days prior to dosing and for the duration of study participation.
* Live vaccine within 14 days prior to dosing and non-live vaccines for 7 days prior study dosing.
* Current enrolment or participation in another clinical trial within the last 30 days before signing consent of current study.
* Presence of hepatitis B surface antigen (HBsAg) or hepatitis C antibody at screening or within 3 months prior to the first dose of study intervention
* A positive pre-study drug/alcohol screen

Where this trial is running

Auckland

• GSK Investigational Site — Auckland, New Zealand (Recruiting)

Study contacts

• Study coordinator: US GSK Clinical Trials Call Center

Conditions Non-alcoholic Fatty Liver Disease; Efimosfermin alfa; Placebo; First time in Asia; Chinese; Japanese; White/Europeans; Pharmacokinetics