A Study of SSS17 in Healthy Subjects

A Single Dose Escalation Study to Investigate the Tolerability, Safety, Pharmacokinetics and Pharmacodynamics of SSS17 in Chinese Healthy Subject

This is a first-in-human, Phase 1, single-center, randomized, single-blind, placebo-controlled, single dose-escalation study to evaluate the safety, tolerability, PK, PD of SSS17 following oral administration in healthy subjects. Approximately 65 subjects (53 receiving active drug and 12 receiving placebo) will participate in this study.

Study Overview

• Status: Unknown
• Conditions: Anemia in Chronic Kidney Diseases
• Intervention / Treatment: Drug: Placebo; Drug: SSS17

Detailed Description

The study will enroll healthy volunteers from a single academic medical center in China. All participants will be informed about the study and potential risks and required to provide written informed consent prior to undergoing study-related procedures.

The improved Fibonacci dose escalation design will be implemented. The protocol specifies 10 mg, oral, one time for the first cohort without placebo control. Successive cohorts will be given doses up to 540 mg with placebo parallel control. Only no observation meets the criteria under stop rules, dose will escalate to the next higher level.

The study will be divided into 2 stages: 1st period (fast) and 2nd period(fed).

First period (fast): Subjects will be allocated 1:4 to receive placebo or SSS17, which will be administered by oral route. At each dose, tolerability, safety, PK and PD characteristics will be investigated.

Second period (fed): in order to investigate the effects of food on PK and PD of SSS17. Subjects in one cohort will be administered again after meal on Day15. The accurate dose will be adjusted according to the findings in 1st period (fast)

• Study Type: Interventional
• Enrollment (Anticipated): 65
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hongzhou Lu, Ph.D; Phone Number: (021)37990333-5278; Email: jigouban@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201203
      • Shanghai Public Health Clinical Center
      • Contact: Hongzhou Lu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body weight≥50 for male or ≥45 for female, and BMI between 19.0-26.0 kg/m2
• Good general health as determined by the investigator based on medical history, physical examination, vital signs, 12-lead ECG, clinical laboratory tests and B-type ultrasound test.
• Participants of reproductive potential must agree to utilize reliable methods of contraception from screening to 6 months after the last administration of the study intervention. No plan for sperm (or egg) donation or pregnancy.
• Understand and sign the informed consent.
• Ability to understand and follow study-related instruction

Exclusion Criteria:

• A known allergy to any component of the SSS17 formulation, or allergy history of two kinds of drugs or food
• Medical history or conditions of digestive system.
• Female volunteers who are pregnant, menstrual, lactating or menopause with hormone therapy.
• Eyes diseases, including diabetic retinopathy, age-related macular degeneration.
• Vascular anomalies.
• Drug, alcohol or nicotine addiction.
• Blood donation or bleeding (more than 200 ml). Experience of treatment with EPO or blood transfusion.
• Any findings from the medical examination (including medical history, physical examination, vital signs, laboratory tests and ECG) deviating from normal and deemed by the investigator to be of clinical relevance
• Abnormal results in test of TIBC, serum iron or ferritin
• Acute diseases before administration.
• Other situations that the researcher believes may affect validity judgment or are not suitable for participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation SSS17; Escalating doses of SSS17; single dose administration; different dosage forms (redosing of the SSS17 in one cohort with food on Day15)	Drug: SSS17; SSS17 is a novel small molecule compound which stimulates erythropoiesis through inhibition of hypoxia-inducible factor- prolyl hydroxylases( HIF-PH). It is being developed for the treatment of anemia in patients with chronic kidney disease.
Placebo Comparator: Escalation matching Placebo; Escalating doses of matching placebo; single dose administration; different dosage forms (redosing of matching placebo in one cohort with food on Day15)	Drug: Placebo; matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	assessment AEs by frequency, severity	up to Day14 or 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) of SSS17	Plasma samples will be collected and Cmax will be assessed.	[ up to 48 hours post-dose]
Area under the concentration-time curve (AUC) of plasma concentration of SSS17	Plasma samples will be collected and the AUC from zero to infinity will be assessed.	[ up to 48 hours post-dose]
Time-to-Cmax (Tmax) of SSS 17	Plasma samples will be collected and the Tmax will be assessed from the concentration-time curve.	[ up to 48 hours post-dose]
Elimination terminal half-life (t1/2) of SSS17	Plasma samples will be collected and the t1/2 will be assessed.	[up to 48 hours post-dose]
Total amount of SSS17 excreted in urine over 24 hours (Ae0-24)	Urine sample will be collected at pre-specified intervals and Ae0-24 will be assessed.	only for one cohort (up to 72 hours post-dose)
Fraction of SSS17 excretion during each collection interval (Fe0-24)	Urine sample will be collected at pre-specified intervals and Fe0-24 will be assessed.	only for one cohort (up to 72 hours post-dose)
Total amount of SSS17 excreted in urine over 72 hours (Ae0-72)	Urine sample will be collected at pre-specified intervals and Ae0-72 will be assessed.	only for one cohort (up to 72 hours post-dose)
Fraction of SSS17 excretion during each collection interval (Fe0-72)	Urine sample will be collected at pre-specified intervals and Fe0-72 will be assessed.	only for one cohort (up to 72 hours post-dose)
Renal clearance (CLR) of SSS17	Urine sample will be collected at pre-specified intervals and CLR will be assessed.	only for one cohort (up to 72 hours post-dose)
EPO concentrations	Change of EPO concentrations from baseline following SSS17	up to 168 hours post-dose.
VEGF concentrations	Change of VEGF concentrations from baseline following SSS17	up to 168 hours post-dose.
Change of RTC from baseline	Change of RTC from baseline following SSS17	up to 168 hours post-dose.
Change of RBC from baseline	Change of RBC from baseline following SSS17	up to 168 hours post-dose.
Change of Hgb from baseline	Change of Hgb from baseline following SSS17	up to 168 hours post-dose.
Change of hepcidin from baseline	Change of serum hepcidin concentrations from baseline following SSS17	up to 168 hours post-dose.

Collaborators and Investigators

• Sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: March 19, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 20, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: SYSS-SSS17-UND-I-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No