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Trial registered on ANZCTR


Registration number
ACTRN12616000335493
Ethics application status
Approved
Date submitted
8/03/2016
Date registered
16/03/2016
Date last updated
7/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ISIS 696844 Administered Subcutaneously to Healthy Volunteers
Scientific title
A Masked, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of ISIS 696844 Administered Subcutaneously to Healthy Volunteers
Secondary ID [1] 288565 0
None
Universal Trial Number (UTN)
U1111-1179-3784
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age-Related Macular Degeneration 297690 0
Condition category
Condition code
Eye 297869 297869 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cohort A: 10 mg ISIS 696844 or placebo
Cohort B: 20 mg ISIS 696844 or placebo
- Subjects will receive 2 subcutaneous doses of Study Drug per week during the first 2 weeks (Days 1, 4, 8, 12) and then one (1) subcutaneous dose of Study Drug per week for the next 4 weeks (Days 15, 22, 29, 36) for a total of 8 doses.
Intervention code [1] 293950 0
Treatment: Drugs
Comparator / control treatment
The placebo for this study is 0.9% sterile saline
Control group
Placebo

Outcomes
Primary outcome [1] 297394 0
To evaluate the safety and tolerability of multiple doses of ISIS 696844 administered subcutaneously.
- The safety and tolerability of ISIS 696844 will be assessed by determining the incidence, severity and dose-response relationship of adverse events (AEs) and changes in the laboratory parameters (summaries of changes and counts of shifts from Baseline) by dose. Vital signs and body weight will be monitored throughout the study, and electrocardiograms (ECG) and physical examinations will be conducted periodically to monitor for adverse effects. Safety results in subjects dosed with ISIS 696844 will be compared with those in subjects dosed with placebo.
Timepoint [1] 297394 0
Screening, Day -1, Day 1, 2, 4, 8, 12, 15, 22, 29, 36, 37, 43, 57, 71, 85, 106 and 127
Primary outcome [2] 297395 0
To evaluate the plasma pharmacokinetics of multiple doses of ISIS 696844 administered subcutaneously.
- The plasma pharmacokinetics of ISIS 696844 (conjugated and/or unconjugated equivalent) Cmax, Tmax plasma t1/2 and AUCinfinity will be assessed following multiple-dose subcutaneous administration. In addition, the amount of ISIS 696844 and/or associated metabolites excreted in urine over selected 24-hr intervals (Days 1-2 and 36-37) will be determined, and metabolite identification and profiling may be determined in select samples.
Timepoint [2] 297395 0
Day 1, 2, 4, 8, 12, 15, 22, 29, 36, 37, 43, 57, 71, 85, 106 and 127
Primary outcome [3] 297422 0
To evaluate the plasma pharmacodynamics of ISIS 696844 administered subcutaneously.
- Plasma complement factor B (FB) level will be assessed following multiple-dose subcutaneous administration of Study Drug (ISIS 696844 or placebo).
Timepoint [3] 297422 0
Screening, Day -1, Day 1, 8, 15, 22, 29, 36, 43, 57, 71, 85, 106 and 127
Secondary outcome [1] 321776 0
None
Timepoint [1] 321776 0
None

Eligibility
Key inclusion criteria
1. Must have given written informed consent and be able to comply with study requirements
2. Healthy males or females aged > 25 years at the time of informed consent.
3. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile, abstinent* or, if engaged in sexual relations with a female of childbearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent until at least 90 days after the subject’s last dose of Study Drug (ISIS 696844 or placebo)
4. Body weight > 50 kg at the time of informed consent
Minimum age
25 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Clinical significant abnormalities in medical history, lab tests or physical exam
2 Abnormalities in complement.
3. Known history of or positive test for human immunodeficiency (HIV), hepatitis C or hepatitis B
4. Treatment with another Study Drug, biological agent, or device within one-month of screening
5. Use of concomitant drugs unless authorized by the Sponsor Medical Monitor
6. Smoking > 10 cigarettes a day

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)
Centralized Randomization by unblinded Pharmacist
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block Randomization
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

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 outside Australia
Country [1] 7599 0
New Zealand
State/province [1] 7599 0
Christchurch
Country [2] 7600 0
New Zealand
State/province [2] 7600 0
Auckland

Funding & Sponsors
Funding source category [1] 292916 0
Commercial sector/Industry
Name [1] 292916 0
Ionis Pharmaceuticals, Inc.
Address [1] 292916 0
2855 Gazelle Court
Carlsbad, CA 92010
Country [1] 292916 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Ionis Pharmaceuticals, Inc.
Address
2855 Gazelle Court
Carlsbad CA 92010
Country
United States of America
Secondary sponsor category [1] 291692 0
Commercial sector/Industry
Name [1] 291692 0
Infinity Consulting
Address [1] 291692 0
PO Box 105-239
Auckland City 1143
Country [1] 291692 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294436 0
Health and Disability Ethics Committee
Ethics committee address [1] 294436 0
Ministry of Health, Freyberg Building
20 Aitken Street
Wellington, New Zealand 6011
Ethics committee country [1] 294436 0
New Zealand
Date submitted for ethics approval [1] 294436 0
10/02/2016
Approval date [1] 294436 0
03/03/2016
Ethics approval number [1] 294436 0
16/CEN/21

Summary
Brief summary
ISIS 696844 is being developed as a treatment for an eye disease called age-related
macular degeneration (AMD). This study assesses multiple doses of ISIS 696844 in healthy men and women, to learn about: Levels of drug in the blood over time;Safety and side effects of the drug; Effects of the drug on specific cells and proteins in the body, which will give researchers an idea of how well the drug might work; Which dose levels of the drug may be best to use in future clinical trials.

30 healthy men and women will be divided into 2 equal dose groups, and will each receive a total of 8 doses of study drug (or matching placebo) over a 6 week period. The dose levels planned for the study are:
Cohort A: 10 mg study drug or matching placebo;
Cohort B: 20 mg study drug or matching placebo;
Blood tests to measure drug levels and effects on specific proteins will be taken at certain times during the dosing period, and any changes in health will be recorded. Extra participants may be added to a dose level, or additional dose levels may be studied, depending on ongoing results.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63634 0
Dr Richard Robson
Address 63634 0
Christchurch Clinical Studies Trust Limited
31 Tuam Street
Christchurch New Zealand 8011
Country 63634 0
New Zealand
Phone 63634 0
+64 3 372 9477
Fax 63634 0
Email 63634 0
richard@ccst.co.nz
Contact person for public queries
Name 63635 0
Dr Richard Robson
Address 63635 0
Christchurch Clinical Studies Trust Limited
31 Tuam Street
Christchurch, 8011
Country 63635 0
New Zealand
Phone 63635 0
+64 3 3729477
Fax 63635 0
Email 63635 0
richard@ccst.co.nz
Contact person for scientific queries
Name 63636 0
Dr Richard Robson
Address 63636 0
Christchurch Clinical Studies Trust Limited
31 Tuam Street
Christchurch, 8011
Country 63636 0
New Zealand
Phone 63636 0
+64 3 3729477
Fax 63636 0
Email 63636 0
richard@ccst.co.nz

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