NCT01674569

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Oct 2012

Typical duration for phase_1

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 23, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 29, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2012

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2015

Completed
3.4 years until next milestone

Results Posted

Study results publicly available

June 27, 2018

Completed
Last Updated

August 7, 2018

Status Verified

July 1, 2018

Enrollment Period

2.3 years

First QC Date

August 23, 2012

Results QC Date

May 24, 2018

Last Update Submit

July 31, 2018

Conditions

Exudative Macular Degeneration

Keywords

VEGFPDGFAMD

Outcome Measures

Primary Outcomes (1)

  • 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.

    6 months

Study Arms (6)

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

Drug: X-82 oralDrug: 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

Drug: X-82 oralDrug: 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

Drug: X-82 oralDrug: 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

Drug: X-82 oralDrug: 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

Drug: X-82 oralDrug: 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.

Drug: X-82 oralDrug: ranibizumab (Lucentis)

Interventions

X-82 oralDRUG

X-82 oral for 24 weeks or until unacceptable toxicity develops

100 mg X-82 oral QD100 mg X-82 oral alternate days200 mg X-82 oral QD300 mg X-82 oral QD50 mg X-82 oral QD50 mg X-82 oral alternate days
ranibizumab (Lucentis)DRUG

Rescue treatment with intravitreal ranibizumab (Lucentis) as needed

100 mg X-82 oral QD100 mg X-82 oral alternate days200 mg X-82 oral QD300 mg X-82 oral QD50 mg X-82 oral QD50 mg X-82 oral alternate days

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Retina Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

New England Retina Associates

New London, Connecticut, 06320, United States

Location

Elman Retina Group

Baltimore, Maryland, 21237, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Retina Consultants of Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • 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.

    PMID: 28570723RESULT

MeSH Terms

Conditions

Wet Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Macular DegenerationRetinal DegenerationRetinal DiseasesEye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Sr Vice President, Development
Organization
Tyrogenex, Inc
Dan@tyrogenex.com
240-403-7153

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 23, 2012

First Posted

August 29, 2012

Study Start

October 1, 2012

Primary Completion

February 1, 2015

Study Completion

February 1, 2015

Last Updated

August 7, 2018

Results First Posted

June 27, 2018

Record last verified: 2018-07

Data Sharing

IPD Sharing
Will not share

Locations

US(5)