None listed
Conditions
Brief summary
APL-2 is a small peptide coupled to each end of a linear polyethylene glycol (PEG) chain. The peptide portion of the drug binds to complement C3 and is a broad inhibitor of the complement cascade, a biological process that is part of innate immunity. The PEG chain imparts longer residence time in the body after administration of the drug. APL-2 is being developed for the management of paroxysmal nocturnal hemoglobinuria (PNH) and daily SC administration of APL-2 is being investigated in two ongoing studies in patients with PNH. However, daily SC infusions are burdensome. The aim of this study is to evaluate and confirm whether less frequent dosing such as twice or once a week is safe and associated with a pharmacokinetic and pharmacodynamic profile likely to provide clinical benefits comparable to the daily SC infusions. An exploratory objective of the study is to compare the pharmacodynamics (PD) of daily, twice a week, and once a week dose regimens of APL 2 in healthy volunteers. For each subject, the study will consist of: * Screening Visit(s) between Day -28 and Day -14 * Admission into clinic on Day -1 * First APL-2 dose on Day 1 * Discharge from clinic on Day 35 * Follow-up visits on Day 42, 56, and 70 * Exit visit on Day 84 The total duration of each subject’s participation is expected to be approximately 112 days.
Interventions
Subjects in Cohort 1 were randomly assigned to treatment with APL-2 360 mg (4 subjects) or matching placebo (1 subject) by subcutaneous injection (SC) once daily for 28 days. Subjects in Cohort 2 were randomly assigned to treatment with APL-2 1,300 mg (4 subjects) or matching placebo (1 subject) SC twice weekly for 28 days. Subjects in Cohort 3 were randomly assigned to treatment with APL-2 2,600 mg (4 subjects) or matching placebo (2 subjects) SC once per week for 28 days. All subjects in Cohor
Subjects in Cohort 1 were randomly assigned to treatment with APL-2 360 mg (4 subjects) or matching placebo (1 subject) by subcutaneous injection (SC) once daily for 28 days. Subjects in Cohort 2 were randomly assigned to treatment with APL-2 1,300 mg (4 subjects) or matching placebo (1 subject) SC twice weekly for 28 days. Subjects in Cohort 3 were randomly assigned to treatment with APL-2 2,600 mg (4 subjects) or matching placebo (2 subjects) SC once per week for 28 days. All subjects in Cohort 4 were assigned treatment with APL-2 1080 mg (16 subjects) SC twice weekly for 28 days. All subjects in Cohort 5 were assigned treatment with APL-2 1080 mg (8 subjects) SC twice weekly for 28 days. The Subjects will participate in one cohort only. Cohort1 and Cohort 2 were conducted in parallel. Cohort 3 was enrolled after completion of Cohort 1 and Cohort 2; Cohort 4 was enrolled after completion of Cohort 3, and Cohort 5 was enrolled after completion of Cohort 4. Doses were administered by healthcare professionals at the study site. Subjects attended a Screening visit (Day -28 to Day -14), resided in the clinic for 35 days from Day -1 (the day before the first dose) until Day 35, and returned to the clinic for 3 follow-up visits on Day 42, 56, and 70, and for a final exit visit on Day 84.
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 49 kg and less than 91 kg and have a BMI higher than 18.4 kg/m2 and lower than 32.1 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-2 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 Female subjects who are pregnant or lactating
Outcome results
None listed