Enrolling Wet Macular Degeneration Clinical Trials
ATMOSPHERE - Phase III Gene Therapy for nvAMD (Regnxbio)
PI: Dr. Murtaza Adam
Trial testing a drug developed as a potential one-time treatment for wet AMD! Current anti-VEGF therapies require repetitive and inconvenient intraocular injections, typically ranging from every four to eight weeks in frequency, to maintain efficacy. Due to a variety of factors, including inconvenience and discomfort associated with frequent injections in the eye, patient compliance is a significant concern with anti-VEGF therapies. Patients often experience vision loss with reduced frequency of treatment.
- The cells within the eye become a biofactory for the drug we inject!
- Potentially curative treatment for some patients. Phase II trial showed 75% reduction in injections with some patients not requiring any at all.
- Effectiveness 4 years after initial treatment!
- PPV safety profile in line with what we see clinically.
- Lucentis arm can be treated with Eylea if indicated.
- Anti-VEGF treatment (lucentis) via gene therapy vector
- Delivered via standard PPV with sub-retinal injection
2:1 RGX-314 (gene therapy) vs q4w Lucentis or Eylea (to rollover to RGX-314 arm after 1 year)
- Age 50-89
- Pseudophakic eyes only
- Dx nvAMD within past 4 years
- SRF or ME present on OCT at screening
- BCVA 20/25-20/200
- Subfoveal: fibrosis, atrophy, hemorrhage.
- Ocular surgery other than CE+IOL
- H/O pigmentary glaucoma, endophthalmitis, PKP, prior gene-Tx
- Lack of anatomic response 1 week following Lucentis
Pseudophakic nvAMD pts with high treatment burden (q 4-8 weeks)
NON-TREATMENT NAÏVE WET AMD
PRISM: Phase I/II Dose Expansion trial of 4D-150 Gene Therapy for nAMD (4D Therapeutics)
PI: Dr. Murtaza Adam
**ON HOLD – REFER POENTIAL PATIENTS FOR POSSIBLE SCREENS IN 4 – 6 WEEKS
Exciting gene therapy study with intravitreal delivery (with similar mechanism to Adverum) but also includes anti-VEGF C inhibition in addition to aflibercept MOI!
Supplemental treatment with Aflibercept PRN
4D-150 is a gene therapy product vector capsid (AAV.4D-R100) carrying codon-optimized sequence encoding aflibercept protein and miRNA targeting VEGF-C
Dose Expansion phase is closed and Steroid Optimization cohort is filled.
Now enrolling for Population Expansion Phase
- Dose Escalation: 4D-150 6x 1010 vg/eye (n=5) or Aflibercept q8w control arm
- Steroid Optimization: 4D-150 3x 1010 vg/eye (n=5)
- Age 50+
- Diagnosed with CNV secondary to AMD with positive response to anti-VEGF prior to screen
- Population Extension Cohort (ON HOLD)
- Maximum of 6 prior anti-VEGF treatments in last 12 months with at least 1 in injection in the last 12 weeks
- No CST requirement! Only history of anti-VEGF response on prior OCTs x 2 within the last 2 years is required
- BCVA 20/32 – 20/320
- Central fibrosis, GA, RPE rip
- Hx of PDT, retinal detachment, vitrectomy, or glaucoma incisional surgery in study eye (SE)
- Hx of steroid-induced ocular hypertension or glaucoma
- Glaucoma requiring more than 2 topical meds for control (IOP <22mmHG in SE)
- Ocular sx within 6 months of screen; or any YAG laser posterior capsulotomy or glaucoma laser tx within 3 months of screen
- Concurrent topical corticosteroid, systemic steroid/immunosuppression
Non-treatment naive patient with nAMD and 20/30 vision or worse and moderate/low treatment burden.
TREATMENT NAÏVE WET AMD
ShORe: Phase III trial of OPT-302 for nvAMD (Ophthea)
PI: Dr. Curtis Hagedorn
Phase II trial demonstrated superior anatomic outcomes and BCVA gains compared to anti-VEGF monotherapy
All treatment arms receive standard of care monthly anti-VEGF therapy
- Recombinant fusion protein that blocks VEGF-C and VEGF-D activity
- Delivered via intravitreal injection in combination with Lucentis
3 arms: Lucentis q4w + OPT-302 q4w (1), q8w (2), and sham (3)
- Age 50+
- Treatment naïve nvAMD or PCV
- Active CNV on FA and/or fluid on OCT
- BCVA 20/60 – 20/320
- Subfoveal fibrosis/atrophy (+25% of lesion area), or subfoveal hemorrhage (+50% of lesion area)
- Ocular surgery other than CEIOL (PKP, glaucoma sx, RD repair, etc)
- H/O cancer within 3 mo of screening (6 mo for for breast and prostate)
- Lack of anatomic response 2 weeks following Lucentis
Treatment naïve patient with nvAMD
Dry Macular Degeneration Clinical Trials
PARASOL: Phase 2b Trial of JNJ-81201887 for non-foveal Geographic Atrophy due to AMD
PI: Curtis Hagedorn, M.D.
ON HOLD – REFER POENTIAL PATIENTS FOR POSSIBLE SCREENS IN 4 – 6 WEEKS
Potentially single shot to slow vision loss. Eye becomes a 'biofactory', making its own therapeutic medicine. Current treatment for this disease requires monthly or EOM shots forever.
Recombinant adeno-associated virus stereotype 2 (rAAV2) with a transgene encoding soluble CD59 (C5-inhibitor) delivered via intravitreal injection
- Low Dose JNJ-81201887: 8.2x1010vg dose
- High Dose JNJ-81201887 4.1x1011vg dose
- Age 60+
- 20/200 or better vision in study eye. CF or better vision in fellow eye.
- Non-subfoveal GA secondary to AMD with an area measuring 2.5mm2 to 17.5 mm2 from images FAF and SD-OCT
- At least one focal lesion ≥1.25mm2 (0.5 disc area)
- GA can be measured separately from any areas of peripapillary atrophy
- Presence of any pattern of hyper AF in the junctional zone of GA
- GA due to diagnosis other than advanced DAMD
- Significant macular disease (history of CNV in either eye, DME, etc) or macular laser
- Hx of PPV, PKP, glaucoma surgery (trab, TS)
- Uncontrolled glaucoma (IOP >22) and history of steroid response
- Intra/periocular surgery or laser procedure SLT, YAG, within 3 months of screen
- Concurrent ocular dx would req surgery within 18 months of screen
- Open PC except due to YAG capsulotomy
- Hx or presence of intraocular inflammation and/or active infection
- Presence of any diabetic retinopathy
60 years of age or older with GA secondary to AMD
Enrolling Uveitis Clinical Trials
Phase III Trial of RO7200220 for Uveitic Macular Edema (Genentech)
PI: Mark Dacey, M.D.
Intravitreal injection for macular edema from uveitis, potentially novel medication because it contains no steroid, therefor it is unlikely to cause cataracts or glaucoma.
Novel recombinant humanized IL-6 ,monoclonal antibody intravitreal injection
RO7200220 IVT 1.0mg q4w versus 0.25 mg q4w versus sham x 4 doses
- 18+ years of age
- Dx of macular edema associated with non-infectious uveitis (CST ≥ 325µm)
- Dx of active, inactive, acute or chronic NIU of any etiology and any anatomical type
- BCVA 20/30 - 20/400
- Active or latent syphilis, HIV, TB
- Serious acute, or chronic medical illness requiring IV antibiotics within 28 days prior to screening
- Blood transfusion withing 12 months prior to screening
- Major non-ocular surgical procedure within 1 month prior to day 1
- Febrile illness within 1 week prior to day 1
- Hypersensitivity to fluorescein, dilating eye drops, topical anesthetic eye drops
- Prev allergy/hypersensitivity to a biologic ICT agent
Adult & Pediatric patients with UME
Phase IIb Study of Izokibep in Non-infectious, Intermediate, Posterior or Panuveitis
PI: Mark Dacey, M.D.
Izokibep was well-tolerated, having a safety profile consistent with previous studies and the IL-17A inhibitor therapeutic class. Supports hypothesis that izokibep offers greater efficacy with high potency and small size, as well as strategy of evaluating (IL)-17A inhibition’s potential for transformative efficacy.
Izokibep is a potent and selective inhibitor of interleukin (IL)-17A that is being developed for tx of uveitis.
Study intervention (izokibep 160mg QW,izokibep every Q2W or placebo) will be dosed by SC injection.
- Age: 18-75 years
- BCVA: over 20 letters
- Negative TB test at screening
- Receiving tx with oral corticosteroids at a stable dose for at least 2 wks (7.5-40 mg/day) prior to day 1. Treated with 2 weeks of high dose Prednisone that is subsequently tapered over 15 weeks total.
- Active disease defined by the presence of at least 1 of the following criteria in at least 1 eye, despite tx with stable doses of corticosteroids for at least 2 wks prior to day 1.
- Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion.
- ≥ 2+ vitreous haze
- History of ocular sx less than 3 months prior to day 1.
- Planned eye sx during study
- Subject with NPDR/PDR, DME due to diabetic retinopathy, or wet AMD.
- Subject with history of active 12 months or less prior to day 1.
- Subject on Cyclophosphamide 30 days or less prior to day 1.
- Subject with corneal or lens opacity that preludes visualization of the fundus or requires cataract sx during study.
Diagnosed with Non-infectious, Intermediate, Posterior or Pan-uveitis.
Phase IV open-label study of YUTIQ (fluocinolone acetonide intravitreal implant) 0.18 mg for Posterior Uveitis (Eyepoint)
PI: Mark Dacey, M.D.
Fluocinolone Acetonide Intravitreal Implant 0.18 mg
Product and Information
YUTIQ 0.18 mg as an intravitreal injection
- Male or female in good general health at 18 to 70 years of age
- Presence of active, recurrent, unilateral or bilateral non-infectious uveitis affecting the posterior segment (intraocular inflammation) with a duration of at least 3 months from initial diagnosis, as determined by the Investigator. Intermediate or panuveitis will also be allowed if posterior segment involvement is part of the diagnosis
- Presence of macular edema as measured by spectral-domain - optical coherence tomography (SD-OCT) (≥325 microns on Heidelberg SPECTRALIS and ≥315 microns on Zeiss CIRRUS).
- Posterior segment inflammation that has previously demonstrated a clinical response to ≥1 localized corticosteroid treatment
- History of macular edema due to diabetes, retinal vein occlusion (RVO), age-related macular degeneration (AMD), or any non-inflammatory cause
- Toxoplasmosis scar or scar related to previous viral retinitis in the study eye
- Any current retinal detachment or retinoschisis in insertion in the study eye
- Ocular and periocular infections such as diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye, or fungal diseases of ocular structures
- Media opacity precluding evaluation of retina and vitreous
- Radiation to the head or neck within 2 years prior to Screening
- Any systemic condition that requires chronic systemic anti-inflammatory, steroid, or immunosuppressive therapy (subjects on a stable dose of oral prednisone <7.5 mg per day for a non-ocular indication may be included)
- Prior intravitreal treatment with Retisert, ILUVIEN, or YUTIQ (0.18 mg) within 36 months prior to Day 1.
- Prior intravitreal treatment with OZURDEX within 12 weeks prior to Day 1.
- Prior intravitreal treatment with Triesence or TRIVARIS (triamcinolone) within 12 weeks prior to Day 1.
- Peri-ocular or subtenon steroid treatment within 12 weeks prior to Day 1.
- Ocular malignancy in either eye, includin
Patient diagnosed with Posterior-Uveitis