Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000822381
Ethics application status
Approved
Date submitted
1/06/2017
Date registered
5/06/2017
Date last updated
13/10/2020
Date data sharing statement initially provided
13/10/2020
Date results information initially provided
13/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, Single-Dose, Open-Label Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of APL-2
Scientific title
A Phase I, Single-Dose, Open-Label Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of APL-2
Secondary ID [1] 291961 0
None
Universal Trial Number (UTN)
U1111-1197-4016
Trial acronym
AIRIS (Apellis Pharmaceuticals Inc Renal Impairment Study)
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Kidney Disease 303308 0
Condition category
Condition code
Renal and Urogenital 302749 302749 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 298090 0
Treatment: Drugs
Comparator / control treatment
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.
Control group
Active

Outcomes
Primary outcome [1] 302138 0
Serum concentrations of APL-2
Timepoint [1] 302138 0
Baseline and at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, 336, 408, 504, 576, 672, and 1,008 hours after dosing.
Secondary outcome [1] 334915 0
The number and severity of treatment emergent adverse events (TEAEs) following administration of single subcutaneous dose of APL-2.
Timepoint [1] 334915 0
Baseline and at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, 336, 408, 504, 576, 672, and 1,008 hours after dosing.
Secondary outcome [2] 334916 0
Serum concentrations of C3.
The complement cascade is part of the immune system, responsible for killing bacteria that infect the body. Complement component C3 is a protein that plays a key role in activation of the complement cascade.
Timepoint [2] 334916 0
Baseline and at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, 336, 408, 504, 576, 672, and 1,008 hours after dosing.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
None
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Initially 8 subjects will be enrolled into both Cohort 1 (severe renal impaired subjects) and Cohort 2 (matched control group). The sample size of 8 per group is commonly used in such studies.
The screened analysis set will include all subjects who signed the informed consent form and are screened for participation in this study. This set will be used only for the purpose of describing subject disposition.
The safety analysis set will include all subjects who receive the dose of APL-2.
The PK analysis set will include all subjects in the safety analysis set who have at least 1 evaluable (i.e. not impacted by any important protocol deviations or other events) post dose PK measurement.
The PD analysis set will include all subjects in the safety analysis set who at least 1 evaluable (i.e. not impacted by any important protocol deviations or other events) post dose PD measurement.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/09/2017
Actual
15/09/2017
Date of last participant enrolment
Anticipated
31/12/2017
Actual
23/02/2018
Date of last data collection
Anticipated
1/12/2017
Actual
6/04/2018
Sample size
Target
16
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 8947 0
New Zealand
State/province [1] 8947 0

Funding & Sponsors
Funding source category [1] 296475 0
Commercial sector/Industry
Name [1] 296475 0
Apellis Pharmaceuticals Inc
Country [1] 296475 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services Pty Ltd
Address
142 Broadway c/o Alliott Ltd
Newmarket
Auckland 1149
Country
New Zealand
Secondary sponsor category [1] 295431 0
None
Name [1] 295431 0
Address [1] 295431 0
Country [1] 295431 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297697 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 297697 0
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 297697 0
New Zealand
Date submitted for ethics approval [1] 297697 0
25/05/2017
Approval date [1] 297697 0
22/06/2017
Ethics approval number [1] 297697 0
17/STH/85

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74862 0
A/Prof Richard Robson
Address 74862 0
Christchurch Clinical Studies Trust
31 Tuam St
Christchurch 8011
Country 74862 0
New Zealand
Phone 74862 0
+64 3 372 9477
Fax 74862 0
+64 3 372 9478
Email 74862 0
[email protected]
Contact person for public queries
Name 74863 0
Dr Lil Edis
Address 74863 0
Apellis Australia Pty Ltd
Level 16, 120 Edward Street
Brisbane Queensland 4000
Country 74863 0
Australia
Phone 74863 0
+61 447447403
Fax 74863 0
Email 74863 0
[email protected]
Contact person for scientific queries
Name 74864 0
Dr Lil Edis
Address 74864 0
Apellis Australia Pty Ltd
Level 16, 120 Edward Street
Brisbane Queensland 4000
Country 74864 0
Australia
Phone 74864 0
+61 447447403
Fax 74864 0
Email 74864 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.