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)
Overview
- Phase
- Phase 1
- Intervention
- X-82 oral
- Conditions
- Exudative Macular Degeneration
- Sponsor
- Tyrogenex
- Enrollment
- 35
- Locations
- 5
- Primary Endpoint
- Change From Baseline Visual Acuity at 6 Months
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief 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 on fundus examination, fundus photography, fluorescein angiography and optical coherence tomography (OCT).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
Exclusion Criteria
- •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.
- •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.
Arms & Interventions
50 mg X-82 oral alternate days
50 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity develops
Intervention: X-82 oral
50 mg X-82 oral alternate days
50 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity develops
Intervention: ranibizumab (Lucentis)
50 mg X-82 oral QD
50 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria.for 24 weeks or until unacceptable toxicity develops
Intervention: X-82 oral
50 mg X-82 oral QD
50 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria.for 24 weeks or until unacceptable toxicity develops
Intervention: ranibizumab (Lucentis)
100 mg X-82 oral alternate days
100 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria.for 24 weeks or until unacceptable toxicty develops
Intervention: X-82 oral
100 mg X-82 oral alternate days
100 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria.for 24 weeks or until unacceptable toxicty develops
Intervention: ranibizumab (Lucentis)
100 mg X-82 oral QD
100 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs
Intervention: X-82 oral
100 mg X-82 oral QD
100 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs
Intervention: ranibizumab (Lucentis)
200 mg X-82 oral QD
200 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs
Intervention: X-82 oral
200 mg X-82 oral QD
200 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs
Intervention: ranibizumab (Lucentis)
300 mg X-82 oral QD
300 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs.
Intervention: X-82 oral
300 mg X-82 oral QD
300 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs.
Intervention: ranibizumab (Lucentis)
Outcomes
Primary Outcomes
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.