Clinical trial NCT06055777: Study of the Safety, Tolerability, and PK of SZEY-2108 Administered Intravenously to HVs in SAD and MAD Cohorts
Official title: A Randomized, Double-blind, Placebo-controlled Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of SZEY-2108 Administreated as Single and Repeated Intravenous Doses in Chinese Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Infections
Keywords: Healthy volunteers
SZEY-2108
Lead sponsor: Suzhou Erye Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase 1 study was designed to evaluate the safety and tolerability of SZEY-2108 in single and multiple intravenous infusions, the pharmacokinetic profile of SZEY-2108 after single and multiple intravenous infusions, and the effect of exposure to SZEY-2108 after a single intravenous infusion on QT/QTc interval. Metabolites in each biological matrix (blood, urine, feces) and excretion characteristics (feces) after SZEY-2108 were analyzed.

Detailed description: This is a first-in-human, randomized, double-blind, placebo-controlled study consisting of 2 parts. Part 1: Single-dose intravenous infusion dose-escalation trial. A total of 44 \~ 52 healthy adult subjects will be enrolled in Part 1 and they will be administrated with SZEY-2108 or placebo by single intravenous infusion. Part 1 consists of 7 cohorts: 100mg，200mg，500mg, 1000mg, 2000mg，4000mg and the dose of last cohort to be determined. Four subjects will be randomized to SZEY-2108 or placebo at a ratio of 1:1 in the 100mg cohort and eight subjects at a ratio of 3:1 in other each cohort. Time for intravenous infusion is 2h±5 min and it may be extended to 3 h±5 min if intolerance occur in 2000mg and 4000mg cohort.

Subjects will be randomised to receive an intravenous infusion of SZEY-2108 or placebo on the morning of D1, then they will still be hospitalised for safety, tolerability, pharmacokinetic and C-QTc assessment, and finally will discharge the Phase I clinical study centre after completion of all assessments at D3. They are required to return to the study centre at D7 for a safety follow-up visit.

Part 2: Multi-dose intravenous infusion dose-escalation trial According to results of Part 1, administration dose and dosing interval may be adjusted in Part 2.

Thirty healthy adult subjects will be enrolled in Part 2 and they will receive multiple doses of SZEY-2108 or placebo by intravenous infusion. Part 2 consists of 3 cohorts: 1000mg at Q8h，2000mg at Q8h, and one dose level of 1000mg, 1500mg or 2000mg at Q6h. Ten subjects will be randomized to SZEY-2108 or placebo at a ratio of 4:1 in each cohort. Time for intravenous infusion is 2h±5 min and it may be extended to 3 h±5 min if intolerance occur in 2000mg cohort.

Subjects will be randomized to receive an intravenous infusion of SZEY-2108 or placebo at Q8h or Q6h on D1\~D7 and on the morning of D8. They will still be hospitalised for safety, tolerability and pharmacokinetic assessment, and finally will discharge the Phase I clinical study centre after completion of all assessments at D9 or D10 (for faecal retention group). Subjects are required to return to the study centre at D15 for a safety follow-up visit.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 45 years at the time of screening;
* BMI between 19 and 28 kg/m2, and weight for males and females ≥ 50kg and 45kg, respectively;
* No clinical relevant abnormalities
* Sign informed consent

Exclusion Criteria:

* Any clinical significant illness
* Other medical or psychiatric may inappropriate for the study
* Past history of allergic conditions or current comorbid allergies
* Use of any prescription medications within 4 weeks prior to screening or use of any over-the-counter medications, herbs, supplements, and vitamins within 7 days prior to the use of the investigational drug;
* History of cigarette, alcohol or drug abuse
* Abnormal vital signs, such as blood pressure and pulse rate
* Abnormal examination results, such as 12-ECG, eGFR, ALT, AST and TBL
* Positive results of HBsAg, TPPA, HCV-Ab, or HIV-Ab
* Blood loss or donation \> 400ml within 3 months prior to screening
* Pregant or breastfeeding females or subjects unwilling to contraception

Primary outcomes:
measure: Safety of single and multiple ascending doses of SZEY-2108
timeFrame: Part 1: From the time of signed consent through the end of study date which occurs on Day 7±1;Part 2: From the time of signed consent through the end of study date which occurs on Day 15±1
Secondary outcomes:
measure: Assessment of Pharmacokinetic Parameter (plasma): Cmax measurement
timeFrame: In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort)
measure: Assessment of Pharmacokinetic Parameter (plasma): AUC
timeFrame: In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort)
measure: Assessment of Pharmacokinetic Parameter (plasma): Tmax
timeFrame: In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort)
measure: Assessment of Pharmacokinetic Parameter (plasma): t1/2
timeFrame: In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort)
measure: Assessment of Pharmacokinetic Parameter (plasma): CL
timeFrame: In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort)
measure: Assessment of Pharmacokinetic Parameter (urine): SZEY-2108
timeFrame: In Part 1：Day1: baseline ,0 to 4, 4 to 8, 8 to 12 and 12 to 24h ；In Part 2：Day1: baseline,0 to 2, 2 to 4, 4 to 8, 8 to 12 and 12 to 24h.
measure: Quantitative relationship between blood concentration and QTc interval of SZEY-2108.
timeFrame: In Part 1：Before dosing (Baseline) through 24 hours after the dose on Day 1 （The dose groups of 100mg and 200mg were excluded）
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Xiaojie Wu
role: PRINCIPAL_INVESTIGATOR
References: