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
ACTRN12613001303730
Ethics application status
Approved
Date submitted
21/11/2013
Date registered
22/11/2013
Date last updated
8/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety study of PF582 versus Lucentis in patients with age related macular degeneration
Scientific title
A Pilot Phase 1/2, Double Blind, Parallel Group, Controlled Study of the Safety, Tolerability and preliminary Efficacy evaluation of intravitreally administered Pfenex ranibizumab (PF582) biosimilar versus Lucentis (registered trademark) for the treatment of neovascular age related macular degeneration (AMD)
Secondary ID [1] 283638 0
Nil
Universal Trial Number (UTN)
U111111471231
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age related macular degeneration (AMD) 290577 0
Condition category
Condition code
Eye 290969 290969 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
0.05mL of Pfenex ranibizumab (PF582) biosimilar or Lucentis (registered trademark) ranibizumab administered intravitreally (injection in the eye) at Days 1, 28, and 56.
Intervention code [1] 288331 0
Treatment: Drugs
Comparator / control treatment
Lucentis (registered trademark) ranibizumab
Control group
Active

Outcomes
Primary outcome [1] 290949 0
To evaluate the safety and tolerability of PF582, compared to
that of Lucentis (registered trademark) in patients with neovascular AMD. This will be done by assessment of vital signs, physical examination, laboratory blood tests and adverse events. Possible adverse events include: eye irritation/discomfort, redness/itching eye, eye dryness, abnormal sensation in eye; lens clouding; pain/irritation at injection site; increased tear production; ‘floaters’; sore throat, nasal congestion, headache, joint pain, flu, fatigue,
breathlessness, dizziness, pale skin, anxiety, cough, nausea and allergic reactions.
Because PF582 is very similar to Lucentis it is expected to have similar adverse effects.
Timepoint [1] 290949 0
Up to 12 months
Secondary outcome [1] 305655 0
To demonstrate the biosimiliarity between PF582 and the
reference compound (Lucentis) based on pharmacokinetics (PK). This will be done by collection and analysis of PK blood samples.
Timepoint [1] 305655 0
Collected at Day 1 (pre-dose, 1, 2, 4 & 24 hours post dose), Day 7 (predose), Day 14 (predose) and Day 28 (predose)
Secondary outcome [2] 305656 0
To demonstrate the biosimiliarity between PF582 and the
reference compound (Lucentis), based on pharmacodynamics (PD) parameters.
This will be assessed by measuring retinal thickness or central foveal thickness (CFT), assessed by optical coherence tomography (OCT)), Leakage from choroidal neovascularization (CNV) assessed by fluorescein angiography (FA).
Timepoint [2] 305656 0
At screening, Day 1, Day 28, 56, Day 80, Month 6 and Month 12
Secondary outcome [3] 305657 0
To assess immunogenicity by collection and analysing blood samples.
Timepoint [3] 305657 0
Day 1, Day 28, 56, Day 80, Month 6 and Month 12
Secondary outcome [4] 305658 0
Preliminary analysis of efficacy.
This will assessed by change in visual acuity and proportion of patients with a change in visual acuity of 15 letters or more. Visual acuity will be measured using the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol.
Timepoint [4] 305658 0
between Day 1 and Day 80 assessment

Eligibility
Key inclusion criteria
- Presence in the study eye of previously untreated active
neovascularization due to AMD
- Visual acuity between 20/25 and 20/320
- Neovascularization, fluid, or haemorrhage under the fovea
- Fibrosis less than 50% of total lesion area
- At least 1 drusen in either eye or late AMD in fellow eye
- Female participants must be of non-childbearing potential
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous treatment for AMD in study eye
- Other progressive retinal disease in the study eye, or the non-study eye, likely to compromise Visual Acuity assessment.
- Contraindications to injections with Lucentis
- Previous Lucentis treatment
- Any other treatment (photocoagulation, phototherapy, radiotherapy, surgery, thermotherapy) in the last 3 months
- Aphaky, vitrectomy
- Active or suspected ocular or periocular infection
- Active intraocular inflammation
- Active systemic infection
- History of stroke or congestive heart failure
- Any other clinical significant illness or abnormalities that would compromise the safety of the participant
- Inability to comply with study or follow up procedures

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)
Patients who agree to participate and are eligible will be randomised via an interactive web response computer system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
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 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Statistical summaries will primarily be descriptive in nature (e.g., means, standard deviations (SDs), and percentiles). Conclusions concerning the risks and benefits of PF582 will be based upon these descriptive analyses.
All patients who receive any amount of study drug will be
included in the analyses, including those who withdraw
prematurely from the study.
Safety will be assessed through summaries of ophthalmologic
and systemic adverse events, serious adverse events (SAEs), changes in laboratory test results, and changes in vital signs. Laboratory data will be listed, with values outside of normal ranges identified. Vital signs, weight, and other disease-specific data will be listed by patient number and scheduled measurement time. Changes from baseline will be summarised by treatment group.
Efficacy and PD parameters will be listed by patient number and scheduled measurement time. Changes from baseline will be summarised by treatment group.

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] 5651 0
New Zealand
State/province [1] 5651 0
Auckland

Funding & Sponsors
Funding source category [1] 288318 0
Commercial sector/Industry
Name [1] 288318 0
Pfenex Inc.
Address [1] 288318 0
10790 Roselle St
San Diego, CA 92121
USA
Country [1] 288318 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Pfenex Inc.
Address
10790 Roselle St
San Diego, CA 92121
USA
Country
United States of America
Secondary sponsor category [1] 287035 0
None
Name [1] 287035 0
Address [1] 287035 0
Country [1] 287035 0
Other collaborator category [1] 277710 0
Commercial sector/Industry
Name [1] 277710 0
Novotech (Australia) Pty Ltd
Address [1] 277710 0
Level 3, 235 Pyrmont St
Pyrmont NSW 2009
Country [1] 277710 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290213 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 290213 0
1 The Terrace C/- MEDSAFE, Level 6, Deloitte House 10 Brandon Street PO Box 5013 Wellington 6011
Ethics committee country [1] 290213 0
New Zealand
Date submitted for ethics approval [1] 290213 0
12/09/2013
Approval date [1] 290213 0
13/11/2013
Ethics approval number [1] 290213 0
13/CEN/133

Summary
Brief summary
The aim of this study is to test if PF582 (ranibizumab) is safe and similar to Lucentis (ranibizumab).
Participants will have a screening visit to check for eligibility. Eligible participants will receive either PF582 or Lucentis, by injection into one eye on study Day 1, 28 and 56. Visits will be conducted on Day 2, 7, 14 80 and at 6 and 12 months. During the study participants will undergo the following procedures: height, weight and vital signs
(blood pressure, pulse, temperature, breathing rate) measurement; medical and surgical history and concomitant medications; adverse event monitoring; physical examinations; eye tests (reading chart, measurement of retinal thickness [via pictures of the retina] and examination of the eye’s blood vessels, via pictures taken following
injection of a dye into the arm), blood collection and a urine pregnancy test, where applicable.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44482 0
A/Prof Philip Polkinghorne
Address 44482 0
Auckland Eye
8 St Marks Road
Remuera Auckland 1050
Country 44482 0
New Zealand
Phone 44482 0
+64 9 529 2480
Fax 44482 0
+ 64 9 529 2481
Email 44482 0
pjpolk@pjpolk.co.nz
Contact person for public queries
Name 44483 0
Mr Anant Patkar
Address 44483 0
Pfenex Inc.
10790 Roselle St
San Diego, CA 92121
USA
Country 44483 0
United States of America
Phone 44483 0
+1 (858) 352-4400
Fax 44483 0
+1 (858) 352-4602
Email 44483 0
apatkar@pfenex.com
Contact person for scientific queries
Name 44484 0
Mr Anant Patkar
Address 44484 0
Pfenex Inc.
10790 Roselle St
San Diego, CA 92121
USA
Country 44484 0
United States of America
Phone 44484 0
+1 (858) 352-4400
Fax 44484 0
+1 (858) 352-4602
Email 44484 0
apatkar@pfenex.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