Eye DiseasesPhase 1NCT02543229
Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 With or Without Lucentis™ in Patients With Wet AMD
A Phase 1 study testing OPT-302 and Lucentis™ in people with Eye Diseases and Macular Degeneration, run by Opthea Limited at 14 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Eye Diseases, Macular Degeneration, Retinal Diseases
- What is being tested?
- OPT-302 and Lucentis™
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 14 sitesUnited States
- Study dates
- Jul 2015to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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)
- Uncontrolled hypertension ≥180 mmHg systolic or ≥110 mmHg diastolic at baseline
- Uncontrolled diabetes mellitus (Disease must be controlled with hemoglobin A1c (HgbA1c) < 9.0%)
- Clinical evidence of diabetic retinopathies, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye that, in the opinion of the investigator, would be likely to limit improvement in the macular anatomy and/or function
- Pregnancy or lactation
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Opthea Investigative Site
Abilene, Texas, 79606
Opthea Investigative Site
Beverly Hills, California, 90211
Opthea Investigative Site
Bloomfield, New Jersey, 07003
Opthea Investigative Site
Charlotte, North Carolina, 28210
Opthea Investigative Site
Cleveland, Ohio, 44122
Opthea Investigative Site
Fort Myers, Florida, 33912
Opthea Investigative Site
Pensacola, Florida, 32503
Opthea Investigative Site
Phoenix, Arizona, 85014
Opthea Investigative Site
Sacramento, California, 95819
Opthea Investigative Site
Santa Maria, California, 93454
Opthea Investigative Site
West Columbia, South Carolina, 29169
Opthea Investigative Site
Wichita, Kansas, 67214
Opthea Investigative Site
Willow Park, Texas, 76087
Opthea Investigative Site
Winter Haven, Florida, 33800
About this study
Official title: A Phase 1 Dose Escalation Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 in Combination With Ranibizumab in Subjects With Wet AMD
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.
Read more
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
- Being tested
- OPT-302, Lucentis™
- Medical subject headings
- Eye Diseases, Macular Degeneration, Retinal Diseases, Retinal Degeneration, Neovascularization, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPT-302Drug
OPT-302 will be administered by intravitreal injection once every month for 3 months
Lucentis™Drug
Also called Ranibizumab
Lucentis™ (0.5 mg) will be administered by intravitreal injection once every month for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose escalation - Cohort 1 | Experimental | Dose Level 1 of OPT-302 in combination with Lucentis™ Receives: Drug: OPT-302; Drug: Lucentis™ |
| Part 1 Dose escalation - Cohort 2 | Experimental | Dose Level 2 of OPT-302 in combination with Lucentis™ Receives: Drug: OPT-302; Drug: Lucentis™ |
| Part 1 Dose escalation - Cohort 3 | Experimental | Dose Level 3 of OPT-302 in combination with Lucentis™ Receives: Drug: OPT-302; Drug: Lucentis™ |
| Part 1 Dose escalation - Cohort 4 | Experimental | Dose Level 3 of OPT-302 monotherapy Receives: 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™ Receives: Drug: OPT-302; Drug: Lucentis™ |
| Part 2 Dose expansion - Cohort 6 | Experimental | OPT-302 (at MTD or highest dose tested in Part 1) monotherapy Receives: Drug: OPT-302 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Adverse Events)
Subject incidences of ophthalmic and systemic Adverse Events during study and follow-up period
Measured: Up to 1 month after the last dose
Secondary outcomes (7)
Mean change in Best Corrected Visual Acuity (BCVA) from baseline
Mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA from baseline
Measured: 6 months
Mean change in central retinal thickness from baseline
Changes in intra- or sub-retinal fluid measured as mean change in central retinal thickness or macula volume by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: 6 months
Mean change in Choroidal Neovascularization (CNV) lesion area from baseline
Change in CNV size according to fluorescein angiogram
Measured: 6 months
Mean number of retreatment injections of anti-VEGF-A therapy during long term follow-up (week 12 to 24)
Measured: 3 months
Need for 'rescue therapy' with ranibizumab in subjects receiving OPT-302 monotherapy
Measured: 3 months
Assess the Pharmacokinetic profile of OPT-302 alone and in combination with ranibizumab following intravitreal administration
Mean systemic OPT-302 Concentration-Time profile
Measured: Up to 28 days post-dose
Anti-OPT-302 antibody formation
Incidence of anti-OPT-302 antibody formation
Measured: Pre-dose and up to 3 months post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2015 (estimated)
- Study startJul 2015
- Primary completion7 Feb 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Eye DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Opthea Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Research, Study director, Opthea Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02543229
- Sponsor's protocol ID
- OPT-302-1001
- Status last verified
- Nov 2017
- First submitted
- 25 Aug 2015
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 in Combination With Ranibizumab in Subjects With Wet AMD
- ClinicalTrials.gov ID
- NCT02543229
- Acronym / sponsor ID
- OPT-302-1001
- Conditions
- Eye Diseases, Macular Degeneration, Retinal Diseases, Retinal Degeneration, Neovascularization, Pathologic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Opthea LimitedIndustry (pharma, biotech, devices)
- Study start
- Jul 2015
- Primary completion
- 7 Feb 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 7 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1 Dose escalation - Cohort 1 | Experimental | Drug: OPT-302, Drug: Lucentis™Dose Level 1 of OPT-302 in combination with Lucentis™ |
| Part 1 Dose escalation - Cohort 2 | Experimental | Drug: OPT-302, Drug: Lucentis™Dose Level 2 of OPT-302 in combination with Lucentis™ |
| Part 1 Dose escalation - Cohort 3 | Experimental | Drug: OPT-302, Drug: Lucentis™Dose Level 3 of OPT-302 in combination with Lucentis™ |
| Part 1 Dose escalation - Cohort 4 | Experimental | Drug: OPT-302Dose Level 3 of OPT-302 monotherapy |
| Part 2 Dose expansion - Cohort 5 | Experimental | Drug: OPT-302, Drug: Lucentis™OPT-302 (at Maximum Tolerated Dose [MTD] or highest dose tested in Part 1) in combination with Lucentis™ |
| Part 2 Dose expansion - Cohort 6 | Experimental | Drug: OPT-302OPT-302 (at MTD or highest dose tested in Part 1) monotherapy |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OPT-302OPT-302 will be administered by intravitreal injection once every month for 3 months | Drug | 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™Also: RanibizumabLucentis™ (0.5 mg) will be administered by intravitreal injection once every month for 3 months | Drug | Part 1 Dose escalation - Cohort 1, Part 1 Dose escalation - Cohort 2, Part 1 Dose escalation - Cohort 3, Part 2 Dose expansion - Cohort 5 |
Primary outcome
Safety (Adverse Events)
Time frame: Up to 1 month after the last dose
Subject incidences of ophthalmic and systemic Adverse Events during study and follow-up period
7 secondary outcomes
Mean change in Best Corrected Visual Acuity (BCVA) from baseline
Time frame: 6 months
Mean change in central retinal thickness from baseline
Time frame: 6 months
Mean change in Choroidal Neovascularization (CNV) lesion area from baseline
Time frame: 6 months
Mean number of retreatment injections of anti-VEGF-A therapy during long term follow-up (week 12 to 24)
Time frame: 3 months
Need for 'rescue therapy' with ranibizumab in subjects receiving OPT-302 monotherapy
Time frame: 3 months
Assess the Pharmacokinetic profile of OPT-302 alone and in combination with ranibizumab following intravitreal administration
Time frame: Up to 28 days post-dose
Anti-OPT-302 antibody formation
Time frame: Pre-dose and up to 3 months post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Research study director
Opthea Limited
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OPT-302 and Lucentis™ in people with Eye Diseases and Macular Degeneration, run by Opthea Limited at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Adverse Events) (time frame: Up to 1 month after the last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.