A study to assess the safety of increasing single doses of AP003 in healthy adults.
A first-in-human, Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study assessing the safety, tolerability, and pharmacokinetics of AP003 in healthy adult volunteers.
Alltrna, Incorporated
30 participants
Feb 16, 2026
Interventional
Conditions
Summary
This study evaluates the safety and tolerability of a new investigational drug, AP003, in healthy adult volunteers. Participants receive a single dose of AP003 or a placebo, and researchers monitor for side effects, vital signs, and laboratory results. The study also investigates how AP003 is processed in the body.
Eligibility
Inclusion Criteria20
- Age 18-65 years of age (inclusive) at the time of signing informed consent;
- Body mass index (BMI) 18.0-34.9 kg/m2;
- Participant is considered to be in good general health as determined by medical history, laboratory assessments, ECG results, vital sign measurements and physical examination findings at screening;
- Systolic blood pressure in the range of 90 to 160 mm Hg and diastolic blood pressure in the range of 50-95 mm Hg;
- Adequate laboratory parameters as follows:
- a.White blood cell (WBC) count, hemoglobin and platelet count within normal limits, except if deemed not clinically significant by the PI;
- b.Aspartate aminotransferase (AST), alanine aminotransferase (ALT) Less than or equal to 1.5 X upper limit of normal (ULN), Total bilirubin Less than or equal to 1.5 X ULN. If total bilirubin is elevated, direct bilirubin Less than or equal to ULN; Participants with isolated unconjugated hyperbilirubinemia consistent with Gilbert syndrome may be included if all other liver function tests (ALT and AST) are within protocol-specified ranges and direct bilirubin is within normal limits;
- c.Estimated glomerular filtration rate (GFR) greater than or equal to 60 mL/min based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2021);
- No clinically significant abnormalities on ECG and corrected QT interval (QTcF) < 450 msec in males and < 470 msec in females at screening;
- Capable of understanding and providing informed consent, and willing and able to comply with the requirements of the study protocol;
- Female participants:
- a.Must be of non-childbearing potential [i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy)] at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
- b.If of childbearing potential, must:
- i.Have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on admission to the study site on Day 1.
- ii.Agree not to attempt to become pregnant or donate ova from signing the participant informed consent form (PICF) until at least 30 days after the last dose of study drug.
- iii.Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 30 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
- Male participants:
- a.Must agree not to donate sperm from signing the PICF until at least 90 days after the last dose of study drug.
- b.If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception from signing the PICF until at least 90 days after the last dose of study drug.
- c.If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom from signing the PICF until at least 90 days after the last dose of study drug.
Exclusion Criteria12
- Any clinically significant abnormal laboratory value;
- Regular consumption of more than 10 standard alcoholic drinks per week and/or more than 4 standard alcoholic drinks on any one day. One standard drink is 10 grams of pure alcohol and is equivalent to 285 mL beer (4.9% Alc/Vol), 100 mL wine (12% Alc/Vol) or 30mL spirit (40% Alc/Vol);
- Participation in another clinical trial of another investigational agent within 30 days prior to study entry (or 5 half-lives of the agent, whichever is longer);
- Major surgical procedure, acute illness or infection requiring medical intervention within 30 days prior to study entry;
- History of anaphylaxis or other significant allergic reaction which, in the opinion of the PI (or designee), would interfere with the volunteer’s ability to participate in the study;
- Positive urine drug screen for any of the following nonprescription drugs of abuse at screening or baseline: methamphetamines, barbiturates, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinol, cocaine, amphetamines, benzodiazepines or methadone. Positive drug screen for amphetamines, benzodiazepines, or opiates will not be exclusionary if prescribed concomitant medication can justify the result;
- Any clinically significant medical condition that would pose undue risk to participant or confound the interpretation of study results;
- Any use of over-the-counter (OTC) and prescription medications except for paracetamol and ibuprofen at the discretion of the PI;
- Has a known or suspected immune-mediated disease or immunosuppressive condition as determined by medical history and/or physical examination;
- History of active malignancy within the last 3 years prior to screening or during screening, except for adequately treated nonmelanomatous skin carcinoma or cervical carcinoma in situ curatively treated;
- Participant who is pregnant, breastfeeding, or considering pregnancy during the conduct of the study;
- Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) positive or human immunodeficiency virus (HIV) positive. If HCV antibody (Ab) is positive, participant must have negative HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR).
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Interventions
The study intervention is AP003, a synthetic tRNA oligonucleotide encapsulated in a lipid nanoparticle (LNP) formulation containing ionizable lipid and pegylated lipid. AP003 will be administered as a single intravenous infusion over approximately 1 hour (±5 minutes), with doses escalating across sequential cohorts (0.015, 0.05, 0.15, 0.3, 0.6 mg/kg). Prior to infusion, participants will receive premedication to reduce infusion-related reactions: ibuprofen 400 mg orally (or acetaminophen 500 mg orally if contraindicated) and oral or intravenous H1 and H2 antihistamines. The study will enroll 6 participants per cohort, with 2 sentinel participants randomized 1:1 to AP003 or placebo. Subsequent participants in each cohort will be randomized 3:1 to AP003 or placebo following confirmation of no acute safety concerns in sentinel participants. Dose escalation to the next cohort will occur within approximately 4 weeks of dosing of the preceding cohort, following review of available safety data and provided no serious adverse events. Infusions may be slowed, interrupted, or discontinued in response to infusion-related reactions. Participants will undergo monitoring of vital signs, laboratory parameters, ECG, cytokines, complement, and anti-PEG antibodies. Safety, tolerability, and pharmacokinetics will be assessed throughout the study, with follow-up visits up to 2 weeks post-dosing. Mode of delivery: Intravenous infusion in a clinical research unit, individually administered. Number and duration of sessions: Single administration with follow-up visits through Day 14
Locations(1)
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ACTRN12626000194369