None listed
Conditions
Brief summary
APL-2 is a small 13-amino acid cyclic 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. The main route of elimination of APL-2 has not yet been empirically determined; however, it is likely that renal clearance plays an important role. The primary objective of this clinical study is to assess the effect of renal impairment on the pharmacokinetics (PK) of a single 270 mg SC dose of APL 2. Secondary objectives are to assess the safety and tolerability of a single dose of APL 2 in patients with renal impairment, and to assess the effect of renal impairment on serum C3 following a single dose of APL 2. Apellis is conducting other clinical studies to investigate APL-2 as a potential treatment for paroxysmal nocturnal hematuria (PNH), which is an acquired hematological disease characterized by complement-mediated red blood cell (RBC) hemolysis. A significant proportion of patients with PNH have associated renal impairment; however, to date, the clinical studies of APL-2 have excluded patients with renal impairment. Pending the results of the current clinical study, Apellis plans to widen the selection criteria in other clinical studies to include patients with PNH and associated renal impairment. The current clinical study is an open-label, non-randomized, parallel-group study to evaluate the effect of renal impairment on the PK of APL-2 following a single 270 mg SC dose. Two cohorts of 8 subjects will be included. Subjects in Cohort 1 will have severe renal impairment and subjects in Cohort 2 will have normal renal function, but will be matched to the subjects in Cohort 1 on the basis of age, gender, and weight. The study may later be expanded to include cohorts of subjects with mild or moderate renal impairment depending on the PK observed in the first two cohorts. For each subject, the study will consist of: * Screening Visit(s) between Day -21 and Day -7 * Admission into clinic on Day -1 * Single APL-2 Dose on Day 1 * Discharge from clinic on Day 4 * Follow-up visits on Days 5, 6, 7, 8, 11, 15, 18, 22, 25, and 29 * Exit visit on Day 43 The total duration of each subject’s participation is expected to be approximately 64 days.
Interventions
This is a phase I, open-label, non-randomized, parallel-group study to evaluate the effect of renal impairment on the PK of APL-2 . It will be conducted at a single site in New Zealand. The study will be comprised of two cohorts. Eight participants with severe renal impairment will be enrolled in Cohort 1 and eight matched-control participants with normal renal function will be enrolled in Cohort 2. All participants will receive a single subcutaneous injection of 270 mg APL-2.
Safety will be ass
This is a phase I, open-label, non-randomized, parallel-group study to evaluate the effect of renal impairment on the PK of APL-2 . It will be conducted at a single site in New Zealand. The study will be comprised of two cohorts. Eight participants with severe renal impairment will be enrolled in Cohort 1 and eight matched-control participants with normal renal function will be enrolled in Cohort 2. All participants will receive a single subcutaneous injection of 270 mg APL-2. 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) and immunogenicity assessments of APL- 2. Participants will be resident in the Clinic (Christchurch Clinical Studies Trust Ltd) from the day before dosing until 72 hours (Day 4) after dosing. Subjects will return for follow-up visits on Days 5, 6, 7, 8, 11, 15, 18, 22, 25, and 29 and the exit visit on Day 43. The study duration per subject is approximately 64 days with a screening interval of up to 21 days.
Sponsors
Clinical Network Services Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
All Subjects: 1. Body mass index (BMI) greater than or equal to 18.5 and less than or equal to 36.0 kg/m2 2. Willingness to utilize an approved form of contraception Cohort 1 (Severe Renal Impaired Subjects): 1. Screening CLCR <30 mL/min 2. Supine blood pressure less than or equal to 190/105 mmHg 3. Stable renal function Cohort 2 (Matched Control Group): 1.. Screening CLCR greater than or equal to 60 mL/min 2. Supine blood pressure less than or equal to 160/95 mmHg Each subject in Cohort 2 will be matched with an individual subject in Cohort 1.
Exclusion criteria
1. Acute renal failure. 2. History of renal transplant 3. Dialysis or hemofiltration 4. Clinically significant disease or illness (other than renal impairment) 5. Febrile illness/infection within 21 days prior to dosing 6. Human immunodeficiency virus; hepatitis B virus, and/or hepatitis C virus 7. Pregnancy, or lactating/breastfeeding
Outcome results
None listed