Safety Study of PF582 Versus Lucentis in Patients With Age Related Macular Degeneration

Age Related Macular Degeneration (AMD) Clinical Trial

Official 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 Biosimilar Versus Lucentis for the Treatment of Neovascular AMD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02121353
• Other study ID #: PF582-CLIN-001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 17, 2014
• Last updated: May 9, 2016
• Start date: November 2013
• Est. completion date: January 2016

Study information

• Verified date: May 2016
• Source: Pfenex, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: New Zealand: Medsafe
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Age =50 years

• Presence in the study eye (one eye per patient) of previously untreated active subfoveal CNV due to AMD, with presence of leakage, as seen on FA, and of fluid, as seen on spectral-domain OCT, located either within or below the retina, or below the retinal pigment epithelium

• Visual acuity between 20/25 and 20/320 being measured using the Early treatment diabetic retinopathy study (ETDRS) protocol1 (chart at 4 meters) before pupil dilation.

• Neovascularization, fluid, or haemorrhage under the fovea.

• Fibrosis < 50% of total lesion area

• At least 1 drusen (>63µm) in either eye or late AMD in fellow eye.

• Female subjects must be of non-childbearing potential, meeting at least one of the following criteria:

• Amenorrheal for 12 months (Menopause confirmed by FSH and LH levels as defined by the established reference ranges), or taking oral contraception for at least 3 months, or surgically sterile for at least the past 3 months, or Receiving a stable dose of implanted or injectable contraceptive for at least 3 months

Exclusion Criteria:

• Previous treatment for CNV in study eye, including antivascular endothelial growth factor(VEGF) medication

• Other progressive retinal disease in the study eye, or the non-study eye, likely to compromise Visual Acuity assessment.

• Contraindications to injections with Lucentis®

• Sub-retineal Haemorrhage > 50% of lesion

• Fibrosis or retrofoveolar atrophy

• History of retrofoveolar laser photocoagulation

• 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Age Related Macular Degeneration (AMD)
• Macular Degeneration

Intervention

Drug:
• Lucentis
Single-use 2 mL vial designed to deliver 0.05 mL of 10 mg/mL ranibizumab solution. Excipients: Alpha, alpha-trehalose dihydrate; histidine hydrochloride, monohydrate; histidine; polysorbate 20; water for injections Route of Administration: Intra-vitreal
• PF582
Single-use 2 mL vial designed to deliver 0.05 mL of 10 mg/mL ranibizumab solution. Excipients: Alpha, alpha-trehalose dihydrate; histidine hydrochloride, monohydrate; histidine; polysorbate 20; water for injections Route of Administration: Intra-vitreal

Locations

Country	Name	City	State
New Zealand	Auckland Eye 8 St Marks Road Remuera Auckland 1050	Auckland
New Zealand	Eye Institute	Remuera	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Pfenex, Inc

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To demonstrate the biosimiliarity between PF582 and the reference compound (Lucentis), based on pharmacodynamics (PD) parameters.	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).	Up to 12 months	No
Primary	To evaluate the safety and tolerability of PF582	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.	Up to 12 months	Yes
Secondary	To demonstrate the biosimiliarity between PF582 and Lucentis based on PK	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.	up to 12 months	No
Secondary	To demonstrate biosimilarity between PF582 and reference compound (Lucentis)	Preliminary analysis of efficacy, as evaluated by mean change in visual acuity between baseline and Day 80 assessment, and proportion of patients with a change in visual acuity of 15 letters or more	12 months	No