This is a Phase 1b randomized, double-blind, placebo-controlled study to assess the safety and tolerability of a proprietary aKLmRNA formulated in lipid nanoparticles. Approximately 21 subjects will be enrolled. Each subject will receive a total of two injections during the study. The cohort will consist of approximately 21 subjects, with each receiving 0.5 mg aKLmRNA (AKL003) or placebo. Subjects will be randomized in a 2:1 ratio (active treatment:placebo). The placebo will be saline, matching the active treatment in both appearance and volume.
Systemic reactogenicity events, such as fever, headache, myalgia, fatigue, nausea/vomiting, diarrhea, and increased heart rate, will be assessed as adverse events using the WHO grading scale. All subjects will be informed about potential clinical activity and reactogenicity, which may be influenced by increased aKL serum levels or the lipid nanoparticle formulation. Participants will be instructed to contact the study site to schedule an on-site visit in case of any unexpected adverse event (unscheduled visit, see Schedule of Activities table). All such occurrences will be documented as part of the drug candidate's safety evaluation. Subjects will provide self-reported data on clinical activity, duration, and effects via a digital diary and in-person assessments during scheduled clinic visits. Additionally, they will be provided with an electronic memory aid for daily symptom tracking throughout the study. Participants will also complete a Quality-of-Life Impact Questionnaire (QOLIQ) at baseline and weekly throughout the study. Furthermore, continuous monitoring of heart rate, heart rate variability, and sleep quality will be conducted using a minimally invasive Oura ring. Participants randomized to placebo who successfully complete the randomized Phase I study may be offered participation in an optional open-label extension to receive Klotho. The purpose of the open-label extension is to provide access to the investigational product and to collect additional safety and pharmacokinetic data. Participation in the open-label extension is voluntary and subject to predefined eligibility criteria and safety review. Data from the open-label extension will be analyzed separately and will not contribute to the primary analysis of the randomized Phase I study. Participants randomized to placebo in the randomized Phase I study will not receive investigational product during the blinded treatment period. In order to provide eligible participants access to Klotho after completion of the randomized study phase and to collect additional safety and pharmacokinetic data, an optional open-label extension (OLE) is planned. The open-label extension is not intended to evaluate efficacy and is not part of the primary analysis of the randomized Phase I study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
21
Each subject will be treated every 4 weeks for a total of 2 times with aKLmRNA via i.v.
Each subject will be treated every 4 weeks for a total of 2 times with TRIS buffer
GARM
Roatán, Bay Islands, Honduras
Overall incidence and severity of unsolicited AEs by treatment group
• To characterize the overall safety and tolerability of multiple administrations of the Investigational Medicinal product (IMP), aKLmRNA (AKL003), in healthy volunteers
Time frame: From first dose through end of study (Day 60)
• Overall incidence and severity of solicited reactogenicity events by treatment group
• To characterize the overall safety and tolerability of multiple administrations of the Investigational Medicinal product (IMP), aKLmRNA (AKL003), in healthy volunteers
Time frame: From first dose through end of study (Day 60)
• Increase in serum aKL levels over the mean of the baseline values until end of study
• To characterize the serum levels of aKL protein as a function of the dose applied and time post administration.
Time frame: Baseline through Day 60
• aKL serum level by treatment group
• To characterize the serum levels of aKL protein as a function of the dose applied and time post administration.
Time frame: Baseline through Day 60
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