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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

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]

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

Condition category

Condition code

Renal and Urogenital

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]

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]

Serum concentrations of APL-2

Timepoint [1]

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]

The number and severity of treatment emergent adverse events (TEAEs) following administration of single subcutaneous dose of APL-2.

Timepoint [1]

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]

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]

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

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Apellis Pharmaceuticals Inc

Address [1]

6400 Westwind Way, Suite A
Crestwood KY 40014

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health and Disability Ethics Committee

Ethics committee address [1]

133 Molesworth Street
 Thorndon
 Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

25/05/2017

Approval date [1]

22/06/2017

Ethics approval number [1]

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

A/Prof Richard Robson

Address

Christchurch Clinical Studies Trust
31 Tuam St
Christchurch 8011

Country

New Zealand

Phone

+64 3 372 9477

Fax

+64 3 372 9478

[email protected]

Contact person for public queries

Name

Lil Edis

Address

Apellis Australia Pty Ltd
Level 16, 120 Edward Street
Brisbane Queensland 4000

Country

Australia

Phone

+61 447447403

Fax

[email protected]

Contact person for scientific queries

Name

Lil Edis

Address

Apellis Australia Pty Ltd
Level 16, 120 Edward Street
Brisbane Queensland 4000

Country

Australia

Phone

+61 447447403

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.

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