A First-in-Human Study of SGB-9768 in Healthy Volunteers
- Conditions
- Complement-mediated DiseasesInflammatory and Immune System - Other inflammatory or immune system disorders
- Registration Number
- ACTRN12624000054516
- Lead Sponsor
- Sanegene Bio New Zealand Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 36
1. Male and female subjects aged 18 to 55 years are included at the time of informed consent.
2. Body mass index between 18 and 32 kg/m2 at screening, inclusive.
3. Physical examination, vital signs, 12-lead electrocardiogram, and laboratory tests be normal or slightly abnormal but not clinically significant according to Investigator’s judgement.
4. Healthy volunteers must be willing to be vaccinated for Neisseria meningitidis (both meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine), Haemophilus influenzae, and Streptococcus pneumoniae before dosing, and willing to receive prophylactic antibiotics as required in the protocol.
5. Female subjects must be non-pregnant or non-lactating.
6. Women of child-bearing potential who are not exclusively in same-sex relationships and males with partners of child-bearing potential must agree to use adequate contraception (As described in Appendix 1) from signing the informed consent until 12 weeks after completion of the follow-up visit.
7. Males must not donate sperm during the study and for 12 weeks after completion of the follow-up visit. Females must not donate egg and for12 weeks after completion of the follow-up visit.
8. Willing to comply with the protocol required visit schedule and visit requirements and provide written informed consent.
1. A history of or current surgical or medical condition that, in the opinion of the Investigator, may put the subject at significant risk (according to Investigator’s judgment) or interfere with the subject’s participation in the clinical study.
2. History of or evidence of tuberculosis.
3. History of recurrent or chronic infections.
4. Subjects with a history of meningococcal infection, or subjects who are exposed to Neisseria meningitidis.
5. History of asplenia or splenectomy.
6. History of abnormalities in complement or hereditary complement deficiency.
7. History of receiving any type of live attenuated vaccine 30 days prior to screening or plans to have such a vaccination over the course of study.
8. Any skin condition and/or tattoo that may interfere the evaluation of safety at the injection site.
9. Presence or suspicion of active viral, bacterial, fungal, or parasitic infection within 14 days before the first study drug administration.
10. History of clinically significant tendinopathy and/or tendon rupture.
11. Serum C3 less than LLN at screening.
12. Positive result of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) antibody, or syphilis at screening.
13. Alanine aminotransferase (ALT), total bilirubin (TBIL), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT) greater than 1.5 × ULN; or, if ALT, TBIL, AST, ALP, or GGT greater than ULN, and less than or equa to 1.5 × ULN, and considered clinically relevant by the Investigator at screening, Day -14, or Day -1.
14. Creatinine (Cr) greater than ULN at screening, Day -14, or Day -1, and considered clinically relevant by the Investigator.
15. QTcF values greater than 450ms for male, and greater than 470ms for female, confirmed by repeated ECGs at screening, Day -14, or Day -1.
16. History of multiple drug allergies or allergic reactions to an oligonucleotide or N-acetylgalactosamine (GalNAc).
17. History of intolerance to subcutaneous (SC) injection or relevant abdominal scarring (surgical, burns, etc.)
18. Received an investigational agent within 30 days or 5-half-lives (whichever is longer) before the first dose of the study drug or being in other clinical study.
19. History or clinical evidence of drug abuse within 12 months before screening or positive screen for drugs of abuse.
20. Used prescribed or over-the-counter medication within 14 days or 5 half-lives (whichever is longer) before the first dose of the study drug unless determined not clinically relevant by the Investigator.
21. Alcohol consumption more than 14 standard drinks per week within one month before screening or positive screen for an alcohol breath test (1 standard drink = 10 grams of alcohol).
22. Regular tobacco use more than 5 cigarettes per day within 3 months before screening.
23. Donate more than 500 mL of blood within 90 days before the first dose of the study drug.
24. Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject’s participation in or completion of the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety and tolerability [Assessed by the incidence of adverse events as evaluated by triplicate 12-lead ECG, physical examination, vital signs (pulse rate and blood pressure by electronic sphygmomanometer, temperature using an aural thermometer, respiratory rate by counting), laboratory safety tests by blood sample collection for assessment of chemistry and hematology, coagulation and urine sample for urinalysis. Baseline, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 131, 141, and 169 days after intervention commencement, and 225, 281, 337 days after intervention commencement if C3 level has not reached 60% of baseline and below normal range.]
- Secondary Outcome Measures
Name Time Method Pharmacokinetic paremeters[Plasma pharmacokinetics parameters include, but not limited to, maximum concentration (Cmax), time to maximum concentration (Tmax), the area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last), AUC from time 0 to infinity (AUC0-inf), and apparent terminal elimination half-life (t½). Urine pharmacokinetics parameters include, but not limited to, the cumulative amount of drug excreted in urine (Ae), fraction of drug recovered in urine (Fe), and renal clearance (CLr). 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48h post-dose];Pharmacodynamic effect[serum complement C3 level Predose, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169 days after intervention commencement. And 225, 281, 337 days after intervention commencement if C3 level has not reached 60% of baseline and below normal range.]