Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 With or Without Lucentis™ in Patients With Wet AMD

NCT02543229 | Completed Phase 1 DMC

• 1 other identifier: OPT-302-1001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this first-in-human study is to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics of OPT-302 administered as monthly intravitreal injections for 3 months with and without Lucentis™ in patients with wet age related macular degeneration (AMD). This study will be conducted in two parts: Part 1 will comprise an open label, sequential dose escalation and Part 2 a randomized dose expansion. OPT-302 is a soluble form of VEGFR-3 comprising the extracellular domains 1-3 of human vascular endothelial growth factor receptor (VEGFR)-3 and the Fc fragment of human IgG1. It functions by binding and neutralizing the activity of vascular endothelial growth factor (VEGF)-C and VEGF-D on endogenous VEGFR-2 and VEGFR-3. VEGF-C and VEGF-D promote blood vessel development (angiogenesis) by binding and activating VEGFR-2 and VEGFR-3. VEGF-C is also a potent inducer of vascular permeability or leakage. Angiogenesis and vascular leakage are key hallmarks of wet AMD. Approved therapies for wet AMD include Eylea™ and Lucentis™ which block the activity of VEGF-A, but not VEGF-C or VEGF-D which are alternate members of the same family of molecules. VEGF-C and VEGF-D can stimulate blood vessel growth and leakage through the same pathway as VEGF-A (via VEGFR-2), as well as through pathways that are independent of VEGF-A (via VEGFR-3). Published studies have also indicated that VEGF-C and VEGF-D play an important role in mediating resistance to therapies that block VEGF-A such as Lucentis™ and Eylea™. Combination therapy with OPT-302 an anti-VEGF-A agent provides a more complete blockade of the VEGF family. This strategy targets functional redundancy in the VEGF pathway and mechanisms of 'resistance' or sub-response to VEGF-A inhibition.

Conditions

Eye Diseases; Macular Degeneration; Retinal Diseases; Retinal Degeneration; Neovascularization, Pathologic

Outcome Measures

Primary Outcomes (1)

• Safety (Adverse Events)

  Subject incidences of ophthalmic and systemic Adverse Events during study and follow-up period

  Up to 1 month after the last dose

Secondary Outcomes (7)

• Mean change in Best Corrected Visual Acuity (BCVA) from baseline

  6 months

• Mean change in central retinal thickness from baseline

  6 months

• Mean change in Choroidal Neovascularization (CNV) lesion area from baseline

  6 months

• Mean number of retreatment injections of anti-VEGF-A therapy during long term follow-up (week 12 to 24)

  3 months

• Need for 'rescue therapy' with ranibizumab in subjects receiving OPT-302 monotherapy

  3 months

Other Outcomes (1)

• Exploratory: Changes in the systemic blood levels of angiogenesis-related biomarkers

  3 months

Study Arms (6)

Part 1 Dose escalation - Cohort 1

EXPERIMENTAL

Dose Level 1 of OPT-302 in combination with Lucentis™

Drug: OPT-302; Drug: Lucentis™

Part 1 Dose escalation - Cohort 2

EXPERIMENTAL

Dose Level 2 of OPT-302 in combination with Lucentis™

Drug: OPT-302; Drug: Lucentis™

Part 1 Dose escalation - Cohort 3

EXPERIMENTAL

Dose Level 3 of OPT-302 in combination with Lucentis™

Drug: OPT-302; Drug: Lucentis™

Part 1 Dose escalation - Cohort 4

EXPERIMENTAL

Dose Level 3 of OPT-302 monotherapy

Drug: OPT-302

Part 2 Dose expansion - Cohort 5

EXPERIMENTAL

OPT-302 (at Maximum Tolerated Dose \[MTD\] or highest dose tested in Part 1) in combination with Lucentis™

Drug: OPT-302; Drug: Lucentis™

Part 2 Dose expansion - Cohort 6

EXPERIMENTAL

OPT-302 (at MTD or highest dose tested in Part 1) monotherapy

Drug: OPT-302

Interventions

OPT-302 DRUG

OPT-302 will be administered by intravitreal injection once every month for 3 months

Part 1 Dose escalation - Cohort 1; Part 1 Dose escalation - Cohort 2; Part 1 Dose escalation - Cohort 3; Part 1 Dose escalation - Cohort 4; Part 2 Dose expansion - Cohort 5; Part 2 Dose expansion - Cohort 6

Lucentis™ DRUG

Lucentis™ (0.5 mg) will be administered by intravitreal injection once every month for 3 months

Also known as: Ranibizumab

Part 1 Dose escalation - Cohort 1; Part 1 Dose escalation - Cohort 2; Part 1 Dose escalation - Cohort 3; Part 2 Dose expansion - Cohort 5

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent
• Age ≥ 50 years of either gender
• Active CNV lesions secondary to AMD (i.e., subretinal or intraretinal fluid on SD-OCT and / or leakage on fluorescein angiography)
• Either no previous treatment in the study eye with IVT anti-VEGF-A therapy (treatment naïve) or prior IVT anti-VEGF-A therapy (previously treated) with sub-optimal response to treatment and the need for additional treatment
• Best corrected visual acuity in the study eye, using ETDRS testing, of 20/320 or better (Snellen equivalent) in Part 1 (dose escalation) and between 20/40 and 20/320 (Snellen equivalent), inclusive, in Part 2 (dose expansion).
• Women of child bearing potential and male subjects with female partners of child bearing potential must be practicing effective contraception during the trial and for at least 3 months following the last dose of study medication

You may not qualify if:

• Previous or concurrent use of systemic anti-VEGF-A agents
• Most recent IVT injection of bevacizumab or ranibizumab \<28 days prior to screening or aflibercept \<42 days prior to screening
• Previous treatment with photodynamic therapy, thermal laser or external beam radiation in the study eye
• Concurrent treatment in either eye for any ocular condition with an investigational drug or device that has not received regulatory approval
• Anatomic damage to the center of the fovea including fibrosis and scarring making up \>50% of total lesion area including the CNV in the study eye
• Geographic atrophy involving the center of the fovea in the study eye
• History or presence of a retinal pigment epithelial tear
• Presence of polypoidal choroidal vasculopathy (if in the opinion of the investigator, anti-VEGF treatment would not be of benefit) or retinal angiomatous proliferation
• Active or recent (within 4 weeks) intraocular inflammation (grade trace or above) in the study eye
• History of rhegmatogenous retinal detachment or macular hole in the study eye
• History of vitrectomy
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
• History of vitreous hemorrhage within 4 weeks prior to screening in the study eye
• History of major ocular surgery within prior 6 months or anticipated within next 3 months following dosing on day 1
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure of \>25 mmHg despite treatment with maximal medical therapy)

Sponsors & Collaborators

• Opthea Limited: lead

Study Sites (14)

Opthea Investigative Site

Phoenix, Arizona, 85014, United States

Location

Opthea Investigative Site

Beverly Hills, California, 90211, United States

Location

Opthea Investigative Site

Sacramento, California, 95819, United States

Location

Opthea Investigative Site

Santa Maria, California, 93454, United States

Location

Opthea Investigative Site

Fort Myers, Florida, 33912, United States

Location

Opthea Investigative Site

Pensacola, Florida, 32503, United States

Location

Opthea Investigative Site

Winter Haven, Florida, 33800, United States

Location

Opthea Investigative Site

Wichita, Kansas, 67214, United States

Location

Opthea Investigative Site

Bloomfield, New Jersey, 07003, United States

Location

Opthea Investigative Site

Charlotte, North Carolina, 28210, United States

Location

Opthea Investigative Site

Cleveland, Ohio, 44122, United States

Location

Opthea Investigative Site

West Columbia, South Carolina, 29169, United States

Location

Opthea Investigative Site

Abilene, Texas, 79606, United States

Location

Opthea Investigative Site

Willow Park, Texas, 76087, United States

Location

MeSH Terms

Conditions

Eye Diseases; Macular Degeneration; Retinal Diseases; Retinal Degeneration; Neovascularization, Pathologic

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Research

  Opthea Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 7, 2015
• Study Start: July 1, 2015
• Primary Completion: February 7, 2017
• Study Completion: September 1, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-11

Locations

US (14)