None listed
Conditions
Brief summary
APL-9 is a PEGylated peptide wherein a small pharmacologically moiety binds to primate complement C3 and exerts a broad inhibition of the complement cascade. The PEG portion of the drug molecule imparts longer residence time in the body after administration of the drug. APL-9 for SC injection is currently in development as a potential treatment for paroxysmal nocturnal hematuria (PNH), which is an acquired hematological disease characterized by complement-mediated red blood cell (RBC) hemolysis, with or without hemoglobinuria, and increased susceptibility to thrombotic episodes, and/or some degree of bone marrow dysfunction. This single ascending dose study is the first study in a planned series of studies for the clinical development of APL-9. The primary objective of the study is to assess the safety and tolerability of single subcutaneous (SC) doses of APL 9 in healthy volunteers. The secondary objective of the study is to assess the pharmacokinetics (PK) of single SC doses of APL 9 in healthy volunteers. An exploratory objective of the study is to assess the pharmacodynamics (PD) of single SC doses of APL 9 when administered to healthy volunteers. The study will recruit 21 subjects in four dose cohorts. Subjects will participate in only one cohort and will receive a single dose of APL 9 or placebo administered subcutaneously. 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 (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. 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 for follow-up visits and the exit visit for subsequent study procedures.
Interventions
Subjects will be randomly assigned to treatment with either a single dose of APL-9 or a single dose of placebo by subcutaneous injection. Doses will be administered by healthcare professionals at the study site. This study will be conducted in 4 sequential cohorts.
The first cohort will receive 90 mg of APL-9 (4 subjects) or placebo (2 subjects).
The second cohort will receive 225 mg of APL-9 (4 subjects) or placebo (1 subject).
The exact doses for the third and fourth cohort will be determined
Subjects will be randomly assigned to treatment with either a single dose of APL-9 or a single dose of placebo by subcutaneous injection. Doses will be administered by healthcare professionals at the study site. This study will be conducted in 4 sequential cohorts. The first cohort will receive 90 mg of APL-9 (4 subjects) or placebo (2 subjects). The second cohort will receive 225 mg of APL-9 (4 subjects) or placebo (1 subject). The exact doses for the third and fourth cohort will be determined after the second cohort has been dosed. The third cohort will receive up to 450 mg of APL-9 (4 subjects) or placebo (1 subject). The fourth cohort will receive up to 450 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 50 kg and less than 95 kg and have a BMI higher than 18.0 kg/m2 and lower than 32.0 kg/m2. Have been vaccinated against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenza 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 60 days or participation in any previous clinical trial with APL-9. Female subjects who are pregnant or lactating.
Outcome results
None listed