Exudative Macular DegenerationPhase 1/2NCT01674569
Pilot Study of X-82 in Patients With Wet AMD
A Phase 1/2 study testing X-82 oral and ranibizumab (Lucentis) in people with Exudative Macular Degeneration, run by Tyrogenex at 5 sites in United States.
Trial summary
The objective of this study is to evaluate the safety and preliminary biologic activity/efficacy of X-82 in patients with wet Age-related Macular Degeneration (AMD). Preliminary efficacy will be assessed by change from baseline in visual acuity, fluorescein leakage, retinal thickness and fibrosis, if detectable, based… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Exudative Macular Degeneration
- What is being tested?
- X-82 oral and ranibizumab (Lucentis)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2012to Feb 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Active choroidal neovascularization (CNV) associated with AMD, as evidenced on fluorescein angiography (FA) and OCT.
- No previous treatment with anti-VEGF therapy or prior anti-VEGF therapy with evidence of response to treatment and the need for additional treatment.
- Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA 20/32 to 20/320 in the study eye(s).
- Adequate bone marrow function.
- PT within the institutional upper limit of normal.
- Adequate hepatic function.
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- Adequate renal function; serum creatinine.
- Ability to swallow oral medication.
- Age ≥ 50 years.
- Willing and able to provide written informed consent, comply with the investigational study protocol and return for all study visits.
Who cannot join
- Previous treatment with photodynamic therapy (PDT) within 4 months of screening in the study eye.
- CNV due to causes other than AMD.
- Geographic atrophy involving the foveal center in the study eye.
- Any retinal vascular disease or retinal degeneration other than AMD in the study eye.
- In the opinion of the investigator, any significant disease in the study eye that could compromise best-corrected visual acuity.
- Cataract surgery in the study eye within three months of screening.
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- Trabeculectomy or aqueous shunt or valve in the study eye.
- Intraocular surgery in the study eye within three months of screening; Nd:YAG capsulotomy or laser iridotomy within 30 days of screening.
- Inadequate pupillary dilation or significant media opacities in the study eye.
- Use of any investigational agent or participation in any other clinical trial of an investigational agent or investigational therapy within thirty (30) days of baseline with the exception of subjects who are participating in the AREDS2 study.
- Females of child bearing potential that are pregnant or not using medically acceptable contraception; males unwilling to take adequate contraceptive measures. Females that are breastfeeding are also excluded.
- Serious allergy to or prior significant adverse reaction to fluorescein.
- Undiagnosed acute illness first observed during screening or between screening and baseline, or severe concurrent medical conditions that, in the investigators judgment, represent a safety concern.
- Severe cardiac disease, symptomatic congestive heart failure, unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization, or arterial thrombosis within 12 months of start of study drug, inadequately controlled hypertension, or ventricular tachyarrhythmias requiring ongoing treatment.
- QTc ≥450 msec or subjects with a history of risk factors for Torsades de Pointes or other clinically significant ECG abnormalities as determined by the investigator.
- Stroke or transient ischemic attack within 12 months of trial entry.
- Clinically significant impaired renal or hepatic function.
- Any major surgical procedure within one month of trial entry.
- Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-82.
- Receiving treatment with anti-coagulants other than 325 mg of aspirin per day.
- Serious active infection, other serious medical condition or any other condition that would impair the ability of the subject to administer the investigational drug or to adhere to the study protocol requirements.
- Presence of any condition which, in the judgment of the investigator, would prevent the subject from completing the study.
- No herbal medications with the exception of bilberry are allowed within 7 days of start of study drug.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Retina Research Institute of Texas
Abilene, Texas, 79606
Elman Retina Group
Baltimore, Maryland, 21237
Retina Vitreous Associates Medical Group
Beverly Hills, California, 90211
Retina Consultants of Houston
Houston, Texas, 77030
New England Retina Associates
New London, Connecticut, 06320
About this study
Official title: A Phase 1 Open-label, Dose Escalation Clinical Trial to Evaluate the Safety and Preliminary Biologic Activity/Efficacy of the VEGFR/PDGFR Inhibitor X-82 Administered Per Os in Subjects With Neovascular Age-related Macular Degeneration (AMD)
The objective of this study is to evaluate the safety and preliminary biologic activity/efficacy of X-82 in patients with wet Age-related Macular Degeneration (AMD). Preliminary efficacy will be assessed by change from baseline in visual acuity, fluorescein leakage, retinal thickness and fibrosis, if detectable, based on fundus examination, fundus photography, fluorescein angiography and optical coherence tomography (OCT).
- Conditions
- Exudative Macular Degeneration
- Being tested
- X-82 oral, ranibizumab (Lucentis)
- Keywords
- VEGF, PDGF, AMD
- Medical subject headings
- Wet Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
X-82 oralDrug
X-82 oral for 24 weeks or until unacceptable toxicity develops
ranibizumab (Lucentis)Drug
Rescue treatment with intravitreal ranibizumab (Lucentis) as needed
| Study group | Role | What they receive |
|---|---|---|
| 50 mg X-82 oral alternate days | Experimental | 50 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity develops Receives: Drug: X-82 oral; Drug: ranibizumab (Lucentis) |
| 50 mg X-82 oral QD | Experimental | 50 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria.for 24 weeks or until unacceptable toxicity develops Receives: Drug: X-82 oral; Drug: ranibizumab (Lucentis) |
| 100 mg X-82 oral alternate days | Experimental | 100 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria.for 24 weeks or until unacceptable toxicty develops Receives: Drug: X-82 oral; Drug: ranibizumab (Lucentis) |
| 100 mg X-82 oral QD | Experimental | 100 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs Receives: Drug: X-82 oral; Drug: ranibizumab (Lucentis) |
| 200 mg X-82 oral QD | Experimental | 200 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs Receives: Drug: X-82 oral; Drug: ranibizumab (Lucentis) |
| 300 mg X-82 oral QD | Experimental | 300 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs. Receives: Drug: X-82 oral; Drug: ranibizumab (Lucentis) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Visual Acuity at 6 Months
The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance.
During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2012 (estimated)
- Study startOct 2012
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Exudative Macular DegenerationStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tyrogenex
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01674569
- Sponsor's protocol ID
- X82-OPH-102
- Status last verified
- Jul 2018
- First submitted
- 23 Aug 2012
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, Liang C, O'Shaughnessy D, Parsons EC, Patel S, Slakter JS, Rosenfeld PJ. Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. JAMA Ophthalmol. 2017 Jul 1;135(7):761-767. doi: 10.1001/jamaophthalmol.2017.1571.
PubMed 28570723
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label, Dose Escalation Clinical Trial to Evaluate the Safety and Preliminary Biologic Activity/Efficacy of the VEGFR/PDGFR Inhibitor X-82 Administered Per Os in Subjects With Neovascular Age-related Macular Degeneration (AMD)
- ClinicalTrials.gov ID
- NCT01674569
- Acronym / sponsor ID
- X82-OPH-102
- Conditions
- Exudative Macular Degeneration
- Keywords
- VEGF, PDGF, AMD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- TyrogenexIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 29 Aug 2012 (estimated)
- Results
- Posted 27 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the safety and preliminary biologic activity/efficacy of X-82 in patients with wet Age-related Macular Degeneration (AMD). Preliminary efficacy will be assessed by change from baseline in visual acuity, fluorescein leakage, retinal thickness and fibrosis, if detectable, based on fundus examination, fundus photography, fluorescein angiography and optical coherence tomography (OCT).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 50 mg X-82 oral alternate days | Experimental | Drug: X-82 oral, Drug: ranibizumab (Lucentis)50 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity develops |
| 50 mg X-82 oral QD | Experimental | Drug: X-82 oral, Drug: ranibizumab (Lucentis)50 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria.for 24 weeks or until unacceptable toxicity develops |
| 100 mg X-82 oral alternate days | Experimental | Drug: X-82 oral, Drug: ranibizumab (Lucentis)100 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria.for 24 weeks or until unacceptable toxicty develops |
| 100 mg X-82 oral QD | Experimental | Drug: X-82 oral, Drug: ranibizumab (Lucentis)100 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs |
| 200 mg X-82 oral QD | Experimental | Drug: X-82 oral, Drug: ranibizumab (Lucentis)200 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs |
| 300 mg X-82 oral QD | Experimental | Drug: X-82 oral, Drug: ranibizumab (Lucentis)300 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Active choroidal neovascularization (CNV) associated with AMD, as evidenced on fluorescein angiography (FA) and OCT.
- No previous treatment with anti-VEGF therapy or prior anti-VEGF therapy with evidence of response to treatment and the need for additional treatment.
- Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA 20/32 to 20/320 in the study eye(s).
- Adequate bone marrow function.
- PT within the institutional upper limit of normal.
Key exclusion criteria (23 listed)
- Previous treatment with photodynamic therapy (PDT) within 4 months of screening in the study eye.
- CNV due to causes other than AMD.
- Geographic atrophy involving the foveal center in the study eye.
- Any retinal vascular disease or retinal degeneration other than AMD in the study eye.
- In the opinion of the investigator, any significant disease in the study eye that could compromise best-corrected visual acuity.
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 |
|---|---|---|
| X-82 oralX-82 oral for 24 weeks or until unacceptable toxicity develops | Drug | 100 mg X-82 oral QD, 100 mg X-82 oral alternate days, 200 mg X-82 oral QD, 300 mg X-82 oral QD, 50 mg X-82 oral QD, 50 mg X-82 oral alternate days |
| ranibizumab (Lucentis)Rescue treatment with intravitreal ranibizumab (Lucentis) as needed | Drug | 100 mg X-82 oral QD, 100 mg X-82 oral alternate days, 200 mg X-82 oral QD, 300 mg X-82 oral QD, 50 mg X-82 oral QD, 50 mg X-82 oral alternate days |
Primary outcome
Change From Baseline Visual Acuity at 6 Months
Time frame: 6 months
The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance. During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28570723Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, Liang C, O'Shaughnessy D, Parsons EC, Patel S, Slakter JS, Rosenfeld PJ. Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. JAMA Ophthalmol. 2017 Jul 1;135(7):761-767. doi: 10.1001/jamaophthalmol.2017.1571.
- Individual participant dataSharing planned: No
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Vitrectomy, Subretinal Tissue Plasminogen Activator (TPA) and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative (Wet) Age-related Macular Degeneration (TIGER).
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing X-82 oral and ranibizumab (Lucentis) in people with Exudative Macular Degeneration, run by Tyrogenex at 5 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 10 inclusion and 23 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 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline Visual Acuity at 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01674569, which also lists 1 linked publication.
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 7 Aug 2018.