A Randomized, Double-blind, Placebo-controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Characteristics of SG301 SC Injection in Single-dose Healthy Subjects and Multiple-dose Systemic Lupus Erythematosus (SLE) Subjects
Overview
- Phase
- Phase 1
- Intervention
- SG301 SC Injection
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Sponsor
- Hangzhou Sumgen Biotech Co., Ltd.
- Enrollment
- 48
- Locations
- 10
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events(Part A and Part B)
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single dose in healthy volunteers and multiple doses of SG301 SC injection in participants with systemic lupus erythematosus (SLE).
Detailed Description
This is a phase I single ascending dose (SAD) study in healthy volunteers and multiple ascending dose (MAD) study in participants with mild or moderate SLE, which consists of Parts A and B. Part A adopts a single-center, open-label, dose escalation trial design, and Part B adopts a multi-center, randomized, double-blind, placebo-controlled trial design to evaluate the safety, tolerability, PK, and immunogenicity, preliminary efficacy of SG301 SC Injection in patients with mild to moderate SLE.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Part A (healthy volunteers)
- •Male healthy adults aged 18-50 years (inclusive);
- •Male participants weighed 50-100 kg (inclusive) with the body mass index of 19.0-27.0 kg/m2 (inclusive);
- •Participants whose partners are of childbearing potential must agree to use effective contraceptive methods throughout the study period and for 6 months following the last dose.
- •Part B (SLE participants)
- •Males or females aged 18-65 years (inclusive);
- •BMI 18.5-30.0 kg/m2 (inclusive);
- •Have diagnosed as SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria, with inadequate response or intolerance to or having relapsed despite the standard treatment;
- •SELENA-SLEDAI score \>4 and ≤12;
- •Serologically ANA and/or anti-ds-DNA antibody tested positive;
Exclusion Criteria
- •Part A (healthy volunteers)
- •Have a history of allergies or likely to be allergic to the investigational drug or any of their ingredients judged by the investigators;
- •Have previously received drugs of the same target (CD38);
- •Have participated in a clinical trial of any drug or medical device within 3 months or 5 half-lives prior to dosing, whichever is longer;
- •Have received any prescription drugs or Chinese herbal medicines within 4 weeks prior to dosing, or any non-prescription or dietary supplements within 2 weeks prior to dosing;
- •Have infections within 2 weeks prior to first dose (including but not limited to viral, bacterial, or fungal infections);
- •Have experienced symptomatic herpes zoster within 3 months prior to dosing;
- •Presence of any of the following diseases assessed by the investigator as abnormal with clinical significance within 6 months prior to dosing;
- •Have a history of cardiovascular diseases within 6 months prior to dosing: chronic congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), myocardial infarction, severe heart diseases (e.g., unstable angina, cardiogenic shock, arrhythmias requiring treatment, heart valve diseases, hypertrophic cardiomyopathy, and rheumatic heart disease, etc.), and familial long QT interval syndrome, etc.;
- •Presence of chronic nervous system symptoms such as dizziness and headache prior to dosing;
Arms & Interventions
SG301 SC
Part A: Dose escalation of SG301 SC will be done in healthy volunteers at 1 mg/kg dose group and 2 mg/kg dose group. Part B: Dose escalation of SG301 SC will be done in Systemic lupus erythematosus subjects in 4 dose groups, namely 2 mg/kg, 4 mg/kg, 8 mg/kg, and 12 mg/kg dose groups. 8 subjects will be randomized to SG301 SC injection in an 8:2 ratio at each dose group.
Intervention: SG301 SC Injection
Placebo
Part B: Dose escalation of SG301 SC will be done in Systemic lupus erythematosus subjects in 4 dose groups, namely 2 mg/kg, 4 mg/kg, 8 mg/kg, and 12 mg/kg dose groups. 2 subjects will be randomized to SG301 SC injection in an 8:2 ratio at each dose group.
Intervention: SG301 SC Injection
Placebo
Part B: Dose escalation of SG301 SC will be done in Systemic lupus erythematosus subjects in 4 dose groups, namely 2 mg/kg, 4 mg/kg, 8 mg/kg, and 12 mg/kg dose groups. 2 subjects will be randomized to SG301 SC injection in an 8:2 ratio at each dose group.
Intervention: SG301 SC Placebo
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events(Part A and Part B)
Time Frame: From baseline through the end of study. Part A: Average 2 months per subject, Part B: Average 5 months per subject.
Number and percentage of AEs which are calculated by worst CTCAE grade by CTCAE 5.
Secondary Outcomes
- RP2D (PartB)(From baseline through the end of study. Average 5 months per subject.)
- Immunogenicity (Part A and Part B)(From baseline through the end of study. Part A: Average 2 months per subject, Part B: Average 5 months per subject.)
- Pharmacokinetics (PK): Cmax (Part A and Part B)(From baseline through the end of study. Part A: Average 2 months per subject, Part B: Average 5 months per subject.)
- PD endpoints: CD38 RO (Part B)(From baseline through the end of study. Average 5 months per subject.)
- Biomarkers evaluation (Part B)(From baseline through the end of study. Average 5 months per subject.)
- Pharmacokinetics (PK): limination half-life (T1/2) (Part A and Part B)(From baseline through the end of study. Part A: Average 2 months per subject, Part B: Average 5 months per subject.)
- Efficacy evaluation (Part B)(From baseline through the end of study. Average 5 months per subject.)
- Evaluation of exploratory measures：BILAG-2004 /PGA (Part B)(From baseline through the end of study. Average 5 months per subject.)
- Evaluation of exploratory measures：immune cell (Part B)(From baseline through the end of study. Average 5 months per subject.)
- Evaluation of exploratory measures：immunoglobulins (Part B)(From baseline through the end of study. Average 5 months per subject.)