None listed
Conditions
Brief summary
APL-9 is formed by a pentadecapeptide (combining a cyclic tridecapeptide active C3-inhibiting moiety and a 2-amino acid linker) covalently coupled to each end of a linear 10 kDa PEG chain, such that there are two peptide moieties per molecule of APL-9. APL-9 is a broad inhibitor of the complement cascade, a biological process that is part of innate immunity and is involved in multiple inflammatory processes. The PEGylation of the molecule imparts slower elimination following administration. APL-9 for intravenous route of administration is currently being considered as a potential treatment for acute conditions that would benefit from rapid and short-term inhibition of the complement system. One of the acute conditions is ischemic stroke. This single ascending dose study is the second in a planned series of studies for the clinical development of APL-9. The primary objective of the study is to assess the pharmacokinetics (PK) of single intravenous doses of APL 9 in healthy volunteers. The secondary objective of the study is to assess the pharmacokinetics of single intravenous doses of APL 9 in healthy volunteers. An exploratory objective of the study is to assess the pharmacodynamics (PD) of single intravenous doses of APL 9 when administered to healthy volunteers. The study will recruit 35 subjects in six dose cohorts. Subjects will participate in only one cohort and will receive a single dose of APL 9 or placebo administered intravenously. 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 PK, PD, and immunogenicity assessment of APL 9. Dose escalation to the next dose level (i.e. next cohort) will not take place until a Safety Monitoring Committee comprised of the Principal Investigator and the Sponsor have determined that adequate safety and tolerability from the previous cohort has been demonstrated to permit proceeding to the next cohort. Subjects will be resident in the clinical facility (Nucleus Network Ltd) from the day before dosing until 168 hours (Day 8) after dosing. Subjects will return to the clinical facility for follow-up visits and the exit visit for subsequent study procedures.
Interventions
Subjects will be randomly assigned to treatment with either a single intravenous (IV) infusion of APL-9 or a single IV infusion of placebo. Doses will be administered by healthcare professionals at the study site and are expected to take approximately 30 min for subjects in the first 4 cohorts; 12 hours for subjects in the 5th cohort, and 24 hours for subjects in the 6th cohort.
This study will be conducted in 5 sequential cohorts.
The first cohort received 30 mg of APL-9 (4 subjects) or place
Subjects will be randomly assigned to treatment with either a single intravenous (IV) infusion of APL-9 or a single IV infusion of placebo. Doses will be administered by healthcare professionals at the study site and are expected to take approximately 30 min for subjects in the first 4 cohorts; 12 hours for subjects in the 5th cohort, and 24 hours for subjects in the 6th cohort. This study will be conducted in 5 sequential cohorts. The first cohort received 30 mg of APL-9 (4 subjects) or placebo (2 subjects). The second cohort received 90 mg of APL-9 (4 subjects) or placebo (2 subjects). The third cohort received 270 mg of APL-9 (4 subjects) or placebo (2 subjects). The fourth cohort received 540 mg of APL-9 (4 subjects) or placebo (2 subjects). The fifth cohort received 540 mg of APL-9 (4 subjects) or placebo (2 subjects). The sixth cohort received 600 mg of APL-9 (4 subjects) or placebo (1 subject).
Sponsors
Clinical Network Services Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Other
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
Medically healthy adults Weigh more than 55 kg and less than 90 kg and have a BMI higher than 18.5 kg/m2 and lower than 32.0 kg/m2. Have been vaccinated against Neisseria meningitidis within two years or willing to receive vaccinations.
Exclusion criteria
Mentally or legally incapacitated or has significant emotional problems or has a history of a significant medical or psychiatric condition or a history of hypersensitivity to compounds related to APL-9 or a history of chronic infections or a recent active infection or recent surgery. Use of any prescription or non-prescription medications, herbal remedies, or vitamin supplements within the last 14 days Blood donation or significant blood loss within previous 56 days or plasma donation within previous 7 days Participation in another clinical trial within the previous 28 days or participation in any previous clinical trial with APL-9. Female subjects who are pregnant or lactating.
Outcome results
None listed