This is a randomized, double-blind, placebo-controlled, single-ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of SAL0195 injection in participants with or without elevated lipoprotein(a) \[Lp(a)\]. Approximately 40 male and female participants aged 18 to 65 years will be enrolled across five planned dose cohorts. Participants will receive a single subcutaneous dose of SAL0195 or matching placebo.
This Phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of a single subcutaneous dose of SAL0195 injection in participants with or without elevated lipoprotein(a) \[Lp(a)\]. The relationship between SAL0195 plasma concentrations and QTc will also be explored, and metabolites in blood and urine will be characterized in selected dose cohorts. The study uses a randomized, double-blind, placebo-controlled, sequential single-ascending-dose design. Five dose levels are planned: 30 mg, 100 mg, 300 mg, 600 mg, and an optional 900 mg dose. Each dose cohort will enroll approximately 8 participants randomized in a 3:1 ratio to SAL0195 or placebo. In the 30 mg cohort, approximately 4 participants without elevated Lp(a) and 4 participants with elevated Lp(a) will be enrolled. Randomization will be stratified by Lp(a) status, with participants within each stratum randomized in a 3:1 ratio to SAL0195 or placebo. The remaining dose cohorts will enroll participants with elevated Lp(a) and will use block randomization in a 3:1 ratio. Each participant will receive only one dose level. Dose escalation will proceed sequentially from the lowest dose after review of available safety, tolerability, pharmacokinetic, and pharmacodynamic data from the preceding cohort. Participants will be followed through Day 85. Participants whose Lp(a) level remains below 60% of baseline at Day 85 will enter an extended follow-up period with visits every 28 days until Lp(a) returns to at least 60% of baseline, the participant reaches approximately 52 weeks after dosing, or the participant withdraws or is lost to follow-up, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
40
A single 30 mg dose of SAL0195 injection will be administered subcutaneously on Day 1. SAL0195 injection is supplied at a concentration of 200 mg/mL. The preferred injection site is the abdomen, with the upper arm or thigh as alternative injection sites.
A single 100 mg dose of SAL0195 injection will be administered subcutaneously on Day 1. SAL0195 injection is supplied at a concentration of 200 mg/mL. The preferred injection site is the abdomen, with the upper arm or thigh as alternative injection sites.
A single 300 mg dose of SAL0195 injection will be administered subcutaneously on Day 1. SAL0195 injection is supplied at a concentration of 200 mg/mL. The preferred injection site is the abdomen, with the upper arm or thigh as alternative injection sites.
A single 600 mg dose of SAL0195 injection will be administered subcutaneously on Day 1. SAL0195 injection is supplied at a concentration of 200 mg/mL. The preferred injection site is the abdomen, with the upper arm or thigh as alternative injection sites.
A single 900 mg dose of SAL0195 injection will be administered subcutaneously on Day 1. SAL0195 injection is supplied at a concentration of 200 mg/mL. The preferred injection site is the abdomen, with the upper arm or thigh as alternative injection sites. This dose cohort is optional and may be initiated based on review of available safety, tolerability, pharmacokinetic, and pharmacodynamic data.
A single dose of matching placebo will be administered subcutaneously on Day 1. The placebo is matched to SAL0195 injection in appearance, odor, packaging, and administration characteristics but contains no active SAL0195. The preferred injection site is the abdomen, with the upper arm or thigh as alternative injection sites.
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs will include respiratory rate, body temperature, pulse rate, and systolic and diastolic blood pressure. Clinically significant abnormalities or worsening from baseline will be summarized by treatment and dose cohort.
Time frame: From baseline through the end of the study, up to Day 365 after dosing.
Incidence and Severity of Treatment-Emergent Adverse Events
The number and percentage of participants with treatment-emergent adverse events (TEAEs), treatment-related adverse events, serious adverse events (SAEs), treatment-related serious adverse events, and adverse events leading to study discontinuation will be summarized by treatment and dose cohort. Adverse events will be assessed for severity and relationship to the study intervention.
Time frame: From study drug administration through the end of the study, up to Day 365 after dosing.
Number of Participants With Clinically Significant Physical Examination Abnormalities
Physical examinations will include assessments of the skin and mucous membranes, superficial lymph nodes, head, neck, chest, abdomen, spine and extremities, nervous system, and other clinically relevant findings. Clinically significant abnormalities or worsening from baseline will be summarized.
Time frame: From baseline through the end of the study, up to Day 365 after dosing.
Number of Participants With Clinically Significant Clinical Laboratory Abnormalities
Clinical laboratory evaluations will include hematology, serum chemistry, urinalysis, and coagulation tests. Clinically significant post-baseline abnormalities or worsening from baseline will be summarized by treatment and dose cohort.
Time frame: From baseline through the end of the study, up to Day 365 after dosing.
Number of Participants With Clinically Significant Twelve-Lead Electrocardiogram Abnormalities
Twelve-lead electrocardiograms will be evaluated for clinically significant abnormalities and changes from baseline. Findings will be summarized by treatment and dose cohort.
Time frame: From baseline through the end of the study, up to Day 365 after dosing.
Incidence and Severity of Injection-Site Reactions
Injection-site reactions, including local signs and symptoms such as erythema, induration, pain, pruritus, and swelling, will be assessed following subcutaneous administration of SAL0195 or matching placebo.
Time frame: From pre-dose through 72 hours after dosing.
Maximum Observed Plasma Concentration of SAL0195 (Cmax)
Maximum observed plasma concentration (Cmax) of SAL0195 following a single subcutaneous dose of SAL0195 injection.
Time frame: Pre-dose through 72 hours after dosing.
Time to Maximum Observed Plasma Concentration of SAL0195 (Tmax)
Time to reach the maximum observed plasma concentration of SAL0195.
Time frame: Pre-dose through 72 hours after dosing.
Area Under the Plasma Concentration-Time Curve to the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time curve of SAL0195 from time zero to the last quantifiable concentration.
Time frame: Pre-dose through 72 hours after dosing.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf)
Area under the plasma concentration-time curve of SAL0195 from time zero extrapolated to infinity.
Time frame: Pre-dose through 72 hours after dosing.
Percentage of AUC Extrapolated to Infinity (AUC_%Extrap)
Percentage of the total AUC extrapolated from the last quantifiable concentration to infinity.
Time frame: Pre-dose through 72 hours after dosing.
Terminal Elimination Half-Life of SAL0195 (t1/2)
Terminal elimination half-life of SAL0195 following a single subcutaneous dose.
Time frame: Pre-dose through 72 hours after dosing.
Terminal Elimination Rate Constant of SAL0195 (λz)
Terminal elimination rate constant of SAL0195 estimated from the terminal phase of the plasma concentration-time profile.
Time frame: Pre-dose through 72 hours after dosing.
Apparent Total Clearance of SAL0195 (CL/F)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Apparent total clearance of SAL0195 following subcutaneous administration.
Time frame: Pre-dose through 72 hours after dosing.
Apparent Volume of Distribution of SAL0195 (Vz/F)
Apparent volume of distribution of SAL0195 during the terminal phase following subcutaneous administration.
Time frame: Pre-dose through 72 hours after dosing.