MMP-9 Inhibition for Recalcitrant Wet AMD

NCT04504123 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 202001041
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Wet (or neovascular) form of age-related macular degeneration (wAMD) is the most common cause of blindness in the Western world. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVI) remain the standard-of-care treatment for wAMD. Previous studies show that about 90% of treated patients lose minimal visual function after 2 years of follow-up. There is still, a subset of 15% patients, incomplete responders, that do not improve and possibly worsen due to the persistence of sub-retinal fluid (with or without intra-retinal fluid) with chronic treatment. The investigators plan to evaluate the effect of oral doxycycline versus placebo on the anatomic and functional outcomes in persistent sub-retinal eye fluid in neovascular wet age-related macular degeneration. This subset are incomplete or non-responders to current anti-VEGF intravitreal therapy.

Conditions

Exudative Macular Degeneration; Wet Age-related Macular Degeneration

Keywords

Active choroidal neovascularization (CNV)

Outcome Measures

Primary Outcomes (1)

• Resolution of the persistent retinal fluid on optical coherence tomography (OCT)

  percentage of patients with retinal fluid-free status

  9 months

Secondary Outcomes (4)

• Change in optical coherence tomography (OCT) central media thickness (CMT)

  9 months compared to baseline

• Change in best corrected visual acuity (BCVA)

  6 months and 9 months compared to Baseline

• Number of intravitreal injections (IVI) administered

  6 months and 9 months

• Inflammatory mediators matrix metalloproteinases MMP-9 and MMP-9 activity

  Baseline, 6 months and 9 months

Other Outcomes (2)

• Ocular Adverse Events

  Baseline to 9 months

• Systemic Adverse Events

  Baseline to 9 months

Study Arms (2)

Doxycycline

EXPERIMENTAL

Participants received doxycycline hyclate 50 mg capsule orally once a day for 6 months

Drug: Doxycycline Hyclate

Placebo

PLACEBO COMPARATOR

Participants received placebo (inactive) capsule orally once a day for 6 months

Drug: Placebo

Interventions

Doxycycline Hyclate DRUG

Doxycycline Hyclate capsules, USP 50 mg

Also known as: Antibiotic - tetracycline compound

Doxycycline

Placebo DRUG

Placebo

Also known as: Inactive substance

Placebo

Eligibility Criteria

• Age: 50 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Wet age-related macular degeneration (wAMD);
• Solely treated with anti-VEGF IVI for active CNV due to wAMD. However, enrolled patients can have other retinal pathologies such as diabetic retinopathy or vein occlusion for which they are not being treated with anti-VEGF IVI;
• Must have persistent sub-retinal with or without intra-retinal fluid due to active CNV from wAMD despite receiving at least three consecutive injections with any anti-VEGF agent;
• Must not have encountered previous side effects from tetracycline medications.

You may not qualify if:

• History of uveitis (including endophthalmitis) or presence of intraocular inflammation;
• Presence of significant epiretinal membrane or macular hole causing distortion of macular anatomy;
• Presence of media opacity preventing discerning of fluid on OCT;
• Any prior ophthalmic surgery (including YAG or retinal laser) within the previous 3 months or anticipated need for any ophthalmic surgery (including cataract extraction) for 9 months following randomization;
• History of peribulbar corticosteroid injection to the studied eye or the fellow eye within the past 6 months;
• History of intravitreal triamcinolone acetonide injection to the studied eye within the past 4 months;
• An ocular condition (other than AMD) is present in the studied eye that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., retinal vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, and Irvine-Gass syndrome);
• CNV due to causes other than wAMD;
• Inability to follow up at the 6th and 9th months time points after recruitment;
• Missing two or more consecutive injections during the six months treatment period;
• Patient requiring imminent need for IVI anti-VEGF medication switch or another treatment intervention, such as photodynamic therapy, during the 9 months trial period;
• Presence of fluid associated with geographic atrophy or disciform scar;
• Any patient with sub-retinal and/or intra-retinal fluid that is not due to CNV (eg, overlying areas of geographic atrophy;
• Any patient actively being actively treated for Irvine-Gass Syndrome.
• Patient with and/or who developed an unstable medical status (e.g., glycemic control, blood pressure, cardiovascular disease, individuals who are unlikely or unable to complete the 9 months trial period) in the opinion of the investigator;

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Hospitals & Clinics Department of Ophthalmology & Visual Sciences

Iowa City, Iowa, 52242, United States

RECRUITING

Related Publications (69)

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MeSH Terms

Conditions

Wet Macular Degeneration

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Elliott H Sohn, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elliott H Sohn, MD

CONTACT

3193563285; elliott-sohn@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Over encapsulation with opaque purple capsule
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Doxycycline Hyclate 50 mg versus placebo capsule

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 7, 2020
• Study Start: November 4, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)