Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000725662
Ethics application status
Approved
Date submitted
2/07/2014
Date registered
8/07/2014
Date last updated
9/12/2020
Date data sharing statement initially provided
9/12/2020
Date results information initially provided
9/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Assess the effect of Subcutaneous APL-2 in Healthy Adult Subjects
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous APL-2 in Healthy Adult Subjects
Secondary ID [1] 284910 0
Nil
Universal Trial Number (UTN)
U1111-1158-2269
Trial acronym
APL-CP0713-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
paroxysmal nocturnal hemoglobinuria (PNH) 292398 0
Condition category
Condition code
Blood 292693 292693 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be randomly assigned to treatment with either a single subcutaneous injection of APL-2 or a single subcutaneous injection of placebo. This study will be conducted in 6 sequential cohorts.
The first cohort will receive 45 mg of APL-2 (4 subjects) or placebo (2 subjects).
The second cohort will receive 90 mg of APL-2 (4 subjects) or placebo (1 subject).
The third cohort will receive 180 mg of APL-2 (4 subjects) or placebo (1 subject).
The fourth cohort will receive 360 mg of APL-2 (4 subjects) or placebo (1 subject).
The fifth cohort will receive 720 mg of APL-2 (4 subjects) or placebo (1 subject).
The sixth cohort will receive 1,440 mg of APL-2 (4 subjects) or placebo (1 subject).
Intervention code [1] 289729 0
Treatment: Drugs
Comparator / control treatment
Placebo (subcutaneous injection of 5% glucose solution)
Control group
Placebo

Outcomes
Primary outcome [1] 292539 0
The safety and tolerability of single subcutaneous doses of APL-2 when administered to healthy adult subjects.
Throughout the study, routine clinical tests will be conducted, including vital signs, ECGs, and blood and urine tests.
Timepoint [1] 292539 0
Up to 29 days after treatment
Secondary outcome [1] 309170 0
Serum pharmacokinetics of single subcutaneous doses of APL-2 when administered to healthy adult subjects.
Timepoint [1] 309170 0
Serum APL-2 will be assessed before dosing (baseline) and 1, 4, 8, and 12 hours after dosing on Day 1, and then on Days 2, 3, 4, 5, 6, 7, 8, 11, 15, 18, 22, 25, 29 and 43 days after dosing.
Secondary outcome [2] 309171 0
Serum pharmacodynamics of single subcutaneous doses of APL-2 when administered to healthy adult subjects.
Timepoint [2] 309171 0
Assessments of serum complement activation markers will be made throughout the study. There will be three assessments before dosing: 2-4 weeks before, the day before, and the day of dosing, and then assessments 2, 3, 4, 5, 6, 7, 8, 11, 15, 18, 22, 25, 29 and 43 days after dosing.

Eligibility
Key inclusion criteria
Healthy adult male or female subject; body mass index (BMI) between 18.5 and 32.0 kg/m2; weight between 60.0 kg and 80.0 kg.
Minimum age
19 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Subject is mentally or legally incapacitated or has significant emotional problems; or has a history of: clinically significant medical or psychiatric condition or disease, any illness that might confound the results of the study or pose a risk to the subject by their participation in the study, alcoholism or drug abuse, and/or hypersensitivity or idiosyncratic reaction to compounds related to APL-2 or particular antibiotics.
* Infection within the last 4 weeks
* Female subjects who are pregnant or lactating.
* Use of any prescription and non-prescription medications, herbal remedies, or vitamin supplements within the last 14 days, or use of some particular drugs such as St. John’s Wort within the last 28 days, up until the end of the study (paracetamol may be permitted)
* Blood donation or significant blood loss within the past 56 days or plasma donation within the last 7 days.
* Participation in another clinical trial within the past 28 days
* Significant surgery within the past 90 days
* Presence of any scars or tattoos on the abdomen which may obscure the injection site

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A computerised randomisation schedule will be made available to the pharmacy staff. The schedule will list randomisation numbers and treatment names. The pharmacist will refer to the schedule and label syringes with the randomisation number and then fill the syringes with either APL-2 or placebo as per the randomisation schedule. The name of the treatment will not be entered onto the syringe. A study nurse will administer the treatments to the study subjects. Neither the pharmacist nor the nurse administering the drug will be involved in subsequent study procedures.
Subjects who complete the study screening assessments and meet all the eligibility criteria will be assigned a randomization number according to a randomization schedule and will receive the corresponding treatment.
Subjects will be randomized to receive either APL-2 or placebo, maintaining a 1:1 ratio for the sentinels in Cohort 1 and a 3:1 for the remainder of the cohort, and 4:1 ratio in each subsequent cohort.
The planned randomization numbers are:
R1001-R1006 for Cohort 1
R2001-R2005 for Cohort 2
R3001-R3005 for Cohort 3
R4001-R4005 for Cohort 4
R5001-5005 for Cohort 5
R6001-R6005 for Cohort 6.
If a subject needs to be replaced, the replacement randomisation number will be increased by 100, e.g. R2005 will be replaced by R2105. The same treatment will be allocated to the replacement subject.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerised randomisation scheme will be created by a statistician who is not otherwise involved in the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Single ascending dose study in 6 sequential cohorts.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal sample size estimate was performed and the sample size chosen for this study has been determined as adequate to meet the study objectives
The placebo subjects from all cohorts will be pooled into a single placebo group for all summaries and presentations.
Descriptive statistics (arithmetic mean, standard deviation [SD], sample size [N], median, minimum, and maximum) will be calculated for quantitative safety data and frequency counts will be compiled for classification of qualitative safety data.
No formal inferential statistics will be applied to safety assessments.
PK parameters for APL-2 will be computed from the individual serum concentrations-time data, using actual sample times using a non-compartmental approach. PK parameters will be summarized by cohort using descriptive statistics.
Pharmacodynamic data will be summarized using descriptive statistics.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/07/2014
Actual
11/07/2014
Date of last participant enrolment
Anticipated
2/07/2015
Actual
2/07/2015
Date of last data collection
Anticipated
Actual
14/08/2015
Sample size
Target
31
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 8410 0
3181 - Prahran

Funding & Sponsors
Funding source category [1] 289537 0
Commercial sector/Industry
Name [1] 289537 0
Apellis Pharmaceuticals Inc.
Country [1] 289537 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 4, 88 Jephson Street
Toowong QLD 4066
Country
Australia
Secondary sponsor category [1] 288223 0
Commercial sector/Industry
Name [1] 288223 0
Apellis Pharmaceuticals Inc
Address [1] 288223 0
6400 Westwind Way, Suite A, Crestwood, KY 40014
Country [1] 288223 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291277 0
The Alfred Office of Ethics and Research Governance
Ethics committee address [1] 291277 0
Ground Floor, Linay Pavilion
Alfred Hospital
Commercial Rd, Melbourne
Victoria, 3004
Ethics committee country [1] 291277 0
Australia
Date submitted for ethics approval [1] 291277 0
26/05/2014
Approval date [1] 291277 0
10/07/2014
Ethics approval number [1] 291277 0
254/14

Summary
Brief summary
APL-2 is an experimental drug being developed by Apellis Pharmaceuticals Inc for the potential use as a treatment for people with a broad range of blood disorders (including paroxysmal nocturnal hemoglobinuria (PNH)) and certain types of auto-immune diseases). PNH is caused by a small change to the individual’s genes, which results in red blood cells being broken down prematurely. People with PNH typically feel tired and often see some blood in their urine. The condition is unfortunately progressive with sufferers needing increasing medical care, with an average life expectancy of only 10 years after diagnosis. The currently available treatments are insufficient to deal with this complex disease with most patients not fully responding to the treatments. APL-2 works in a different way to the drugs that are currently approved, and has been shown in laboratory studies to prevent the breakdown of red blood cells and keep them healthy. It is hoped that APL-2 will help improve the quality of life and reduce the severity of the condition for PNH sufferers.
This study will be first study of APL-2 in humans. The assessments of the safety, tolerability, pharmacokinetics, and pharmacodynamics following administration of single doses of APL-2 will guide decisions to further develop the drug.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49638 0
Dr Jason Lickliter
Address 49638 0
Nucleus Network Limited
Level 5, Burnet Tower,
AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004
Country 49638 0
Australia
Phone 49638 0
+61 3 9076 8906
Fax 49638 0
Email 49638 0
[email protected]
Contact person for public queries
Name 49639 0
Dr Phuong Le
Address 49639 0
Nucleus Network Limited
Level 5, Burnet Tower,
AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004
Country 49639 0
Australia
Phone 49639 0
+61 3 9076 9017
Fax 49639 0
Email 49639 0
[email protected]
Contact person for scientific queries
Name 49640 0
Dr Pascal Deschatelets
Address 49640 0
Apellis Pharmaceuticals
6400 Westwind Way, Suite A
Crestwood, KY 40014
Country 49640 0
United States of America
Phone 49640 0
+1 502 241 4114
Fax 49640 0
Email 49640 0
[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

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

Documents added automatically
No additional documents have been identified.