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Trial registered on ANZCTR


Registration number
ACTRN12614001299695
Ethics application status
Approved
Date submitted
1/12/2014
Date registered
11/12/2014
Date last updated
18/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Assess the effect of once-daily Subcutaneous APL-2 in Healthy Adult Subjects
Scientific title
A Phase 1, Double blind, Randomized Study to assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Subcutaneous APL-2 Dose in Healthy Volunteers
Secondary ID [1] 285765 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
APL-CP1014
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal nocturnal hemoglobinuria (PNH) 293649 0
Condition category
Condition code
Blood 293946 293946 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be randomly assigned to treatment with either daily subcutaneous injections of APL-2 or daily subcutaneous injections of placebo, for 28 consecutive days. This study will be conducted in 4 sequential cohorts. The first cohort will receive 30 mg of APL-2 (4 subjects) or placebo (1 subject).
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 270 mg of APL-2 (4 subjects) or placebo (1 subject).
Injections will be administered by a study nurse or physician.
A second study nurse or physician will observe and document the injection procedure. An independent monitor will review the documentation and verify that each injection was correctly administered.
Intervention code [1] 290726 0
Treatment: Drugs
Comparator / control treatment
Placebo (subcutaneous injection of 5% glucose solution)
Control group
Placebo

Outcomes
Primary outcome [1] 293722 0
The safety and tolerability of multiple 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] 293722 0
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 42, 56, 70, and 84 days after treatment
Secondary outcome [1] 311662 0
Pharmacokinetics of multiple subcutaneous doses of APL-2 when administered to healthy adult subjects.


Timepoint [1] 311662 0
Serum APL-2 1, 2, 3, 4, 5, 6, 8, 15, 22, 28, 29, 35, 42, 56, 70, and 84 days after treatment
Secondary outcome [2] 311663 0
Pharmacodynamics of multiple subcutaneous doses of APL-2 when administered to healthy adult subjects.
Timepoint [2] 311663 0
Serum complement activation markers 8, 15, 22, 29, 35, 42, 56, 70, and 84 days after treatment

Eligibility
Key inclusion criteria
Healthy adult male or female subject; body mass index (BMI) greater than or equal to 18.5 and less than or equal to 32.0 (kg/m2); weight greater than or equal to 60.0 kg and less than or equal to 80.0 kg
Minimum age
18 Years
Maximum age
55 Years
Gender
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.
* Subject has a history of chronic infections (eg COPD) or any active infection
* 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
* Subjects who have participated in the Single Ascending Dose study with APL-2

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 4:1 ratio in each cohort.
The planned randomization numbers are:
R1001-R1005 for Cohort 1
R2001-R2005 for Cohort 2
R3001-R3005 for Cohort 3
R4001-R4005 for Cohort 4.
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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Multiple ascending dose study in 4 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
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3229 0
The Alfred - Prahran
Recruitment postcode(s) [1] 9007 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 290333 0
Commercial sector/Industry
Name [1] 290333 0
Apellis Pharmaceuticals Inc
Address [1] 290333 0
6400 Westwind Way, Suite A
Crestwood, KY 40014
Country [1] 290333 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] 289050 0
Commercial sector/Industry
Name [1] 289050 0
Apellis Pharmaceuticals Inc
Address [1] 289050 0
6400 Westwind Way, Suite A
Crestwood, KY 40014
Country [1] 289050 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292038 0
The Alfred, Office of Ethics and Research Governance
Ethics committee address [1] 292038 0
Ground Floor, Linay Pavilion
Alfred Hospital, Commercial Rd, Melbourne, Victoria, 3004
Ethics committee country [1] 292038 0
Australia
Date submitted for ethics approval [1] 292038 0
27/10/2014
Approval date [1] 292038 0
09/12/2014
Ethics approval number [1] 292038 0
496/14

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 animal 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.
In this study, multiple ascending doses of APL 2 will be assessed in healthy volunteers. 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 53178 0
Dr Jason Lickliter
Address 53178 0
Nucleus Network Limited
Level 5, Burnet Tower,
AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004
Country 53178 0
Australia
Phone 53178 0
+61 3 9076 8960
Fax 53178 0
Email 53178 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 53179 0
Dr Tristan Iseli
Address 53179 0
Nucleus Network Limited
Level 5, Burnet Tower,
AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004
Country 53179 0
Australia
Phone 53179 0
+61 3 9076 9014
Fax 53179 0
Email 53179 0
t.iseli@nucleusnetwork.com.au
Contact person for scientific queries
Name 53180 0
Dr Pascal Deschatelets
Address 53180 0
Apellis Pharmaceuticals
6400 Westwind Way, Suite A
Crestwood, KY 40014
Country 53180 0
United States of America
Phone 53180 0
+1 502 241 4114
Fax 53180 0
Email 53180 0
pascal@apellis.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary