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

Sponsor

Pfenex, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT02121353

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

12.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration (AMD)	Drug: Lucentis Drug: PF582	Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF582 PF582 is provided as single use vials and will be administered by intra-vitreal injection on Day 1, 28 and 56.	Drug: 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 Other Names: ranibizumab
Active Comparator: Lucentis Lucentis® is provided as single use vials and will be administered by intra-vitreal injection on Day 1, 28 and 56.	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 Other Names: ranibizumab

Arm

Intervention/Treatment

Experimental: PF582

PF582 is provided as single use vials and will be administered by intra-vitreal injection on Day 1, 28 and 56.

Drug: 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

Other Names:

ranibizumab

Active Comparator: Lucentis

Lucentis® is provided as single use vials and will be administered by intra-vitreal injection on Day 1, 28 and 56.

Drug: Lucentis

Other Names:

ranibizumab

Outcome Measures

Primary Outcome Measures

To evaluate the safety and tolerability of PF582 [Up to 12 months]
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.

Secondary Outcome Measures

To demonstrate the biosimiliarity between PF582 and Lucentis based on PK [up to 12 months]
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.
To demonstrate biosimilarity between PF582 and reference compound (Lucentis) [12 months]
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

Other Outcome Measures

To demonstrate the biosimiliarity between PF582 and the reference compound (Lucentis), based on pharmacodynamics (PD) parameters. [Up to 12 months]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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