None listed
Conditions
Brief summary
APL-2 is an experimental drug being developed by Apellis Pharmaceuticals Inc for potential use as a treatment for people with ischemia-reperfusion injuries. In this study, single doses of APL-2 will be assessed in healthy volunteers. Assessments of safety, tolerability, pharmacokinetics, and pharmacodynamics parameters following administration of single doses of APL-2 will guide decisions to further develop the drug.
Interventions
This is a phase I, double-blind, randomized, placebo controlled, single ascending dose study of APL-2 administered intravenously to healthy volunteers. It will be conducted at a single site in Australia. The study will recruit four dose cohorts each comprising four subjects receiving APL-2 and one subject receiving placebo. A fifth cohort may be recruited if required.
Subjects will receive a single intravenous bolus injection of APL-2 administered over 30 minutes. Meals will be restricted from 1
This is a phase I, double-blind, randomized, placebo controlled, single ascending dose study of APL-2 administered intravenously to healthy volunteers. It will be conducted at a single site in Australia. The study will recruit four dose cohorts each comprising four subjects receiving APL-2 and one subject receiving placebo. A fifth cohort may be recruited if required. Subjects will receive a single intravenous bolus injection of APL-2 administered over 30 minutes. Meals will be restricted from 1 hour prior to dosing to 4 hours after dosing. Safety will be assessed throughout the study; serial blood samples and urine samples will be collected for these assessments. Blood samples will also be collected for the pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity assessments of APL- 2. The safety, PK, PD and immunogenicity profiles of APL-2 will be compared to placebo. On Day 1 of each cohort, 4 subjects will receive APL-2 and 1 will receive placebo. APL- 2 will be supplied as a sterile solution in acetate-buffered saline at a concentration of 24 mg/mL. Dose escalation to the next dose level (i.e. next cohort) will not take place until a Safety Monitoring Committee (SMC) comprised of the Principal Investigator (PI), the Medical Monitor, and the Sponsor have determined that adequate safety and tolerability from the previous cohort has been demonstrated to permit proceeding to the next cohort. The planned dose for cohorts 1 and 2 is 200 mg and 600 mg respectively, the dose for cohorts 3 and 4 will be determined by the SMC following their review of safety, PK and PD data from the previous cohort(s). Subjects will be resident in the Unit (Nucleus Network Ltd) from the day before dosing until 168 hours (Day 8) after dosing. Subjects will return for follow-up visits on Days 15, 22 and 29 and the exit visit on Day 43 for subsequent study procedures. The study duration per subject is approximately 70 days with a screening interval of up to 28 days. Interim PK analyses will be performed to guide the dose-escalation decision and to reconsider the sampling time points as the study progresses.
Sponsors
Clinical Network Services Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female, 2. Continuous non-smoker for at least 3 months prior to dosing. 3. Weigh more than or equal to 55 kg and less than or equal to 90 kg and have a Body Mass Index (BMI) of greater than or equal to 18.5 and less than or equal to 32.0 kg/m2. 4. Medically healthy with no clinically significant screening results as deemed by the principal investigator (PI). 5. Able to provide documentary evidence of vaccination with Neisseria menigitides types A, C, W, Y and B, Streptococcus pneumoniae (PCV13 or PPSV23) and Haemophilus influenza (Hib) within 2 years of dosing, or willing to receive vaccinations against Neisseria menigitides, PCV13 and Hib vaccines at least two weeks prior to dosing. 6. Women of child bearing potential (WOCBP) must have a negative pregnancy test at screening and during the study and must agree to use protocol defined methods of contraception for the duration of the study. 7. Women of non-childbearing potential (WONCBP) must have undergone one of the protocol defined sterilization procedures at least 6 months prior to dosing or be postmenopausal for at least 1 year prior to dosing and have FSH serum levels consistent with postmenopausal status upon Screening. 8. Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for 3 months after the final dose of APL-2. 10. Willing and able to give informed consent.
Exclusion criteria
1. Mental or legal incapacitation or significant emotional problems at screening or expected during the study in the opinion of the PI. 2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the principal investigator (PI). 3. History of any illness that, in the opinion of the PI, might confound the study results or poses an additional risk to the subject by their participation in the study. 4. History or presence of alcoholism or drug abuse within the past 2 years prior to screening. 5. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product. 6. History of chronic infections or active infection at check-in (as determined by the PI) 7. Pregnant or lactating women. 8. Positive results for the urine drug or alcohol breath test at screening or check-in. 9. Positive urine cotinine at screening or check in. 10. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. 11. Clinically relevant clinical laboratory results at screening or check in, as deemed by the PI. 12. Seated systolic blood pressure less than 90/40 mmHg or greater than 140/90 at screening or greater than 155/90 mmHg at any other assessment prior to dosing. 13. Heart rate lower than 40 bpm or higher than 99 bpm at screening or at any other assessment prior to dosing. 14. QTcF interval greater than 450 msec for males or greater than 470 msec for females, or history of prolonged QT syndrome at screening or prior to dosing. 15. Estimated creatinine clearance (CrCl) less than 90 mL/min (Cockcroft Gault formula)or serum creatinine greater than 1.5 mg/mL (133 µmol/L) at screening. 16. Unable to refrain from or anticipates the use of: -Any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements from 14 days prior to dosing and throughout the study, with the exception of paracetamol. -Any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John’s Wort, for 28 days prior to dosing and throughout the study. 17. Blood donation or significant blood loss within 56 days prior to dosing. 18. Plasma donation within 7 days prior to dosing. 19. Participation in another clinical trial within 28 days prior to dosing. 20. Clinically relevant surgery within 90 days prior to dosing.. 21. Any condition or circumstance, in the opinion of the PI, which may make the subject unlikely to complete the study or comply with study procedures and requirements, or may pose a risk to the subject’s safety. 22. Subjects who have participated in the any study with APL-2.
Outcome results
None listed