Choroidal Neovascularization, Diabetic Macular Edema, Diabetic Retinopathy
Conditions
Brief summary
This is a two-part study. The first part (Stratum I) is an open-label, dose escalation, safety, tolerability and pharmacokinetic study, where active study drug (PF-04523655) will be given to all patients who participate. Stratum I will determine the maximum tolerated dose and any dose-limiting toxicities. The second part (Stratum II) is a prospectively randomized, multi-center, double-masked, dose ranging study evaluating the efficacy and safety of PF-04523655 alone and in combination with ranibizumab versus ranibizumab alone in patients with DME.
Detailed description
Patients will be enrolled concurrently according to one of two sets of criteria designated as Stratum I and Stratum II. 1. Stratum I will enroll up to 24 subjects with low vision, inclusive of possible intermediate doses, in up to 4 cohorts of 3-6 evaluable subjects. 2. Stratum II will enroll approximately 240 subjects with DME 1:1:1:1 in up to 4 cohorts of 60 evaluable subjects.
Interventions
DRUGPF-04523655 (Stratum I)
PF-04523655 (a small interfering RNA) - a single IVT injection
DRUGranibizumab
6 monthly IVT injections of ranibizumab (Stratum II)
DRUGPF-04523655 (Stratum II)
6 monthly IVT injections of PF-04523655 (a small interfering RNA)
Sponsors
Quark Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Stratum I Inclusion Criteria: 1. Visual acuity in the study eye ≤ 20/200. 2. Low visual acuity is the result of an irreversible condition affecting the posterior segment of the study eye. Key Stratum I
Exclusion criteria
1. History of vitrectomy. 2. History of IVT injection in study eye within last 6 months. 3. History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye. 4. History of uveitis or endophthalmitis in either eye. 5. Any active inflammatory condition in study eye. 6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing. 7. Any medical condition, concomitant therapy or previous incisional or laser surgery that, in the opinion of the Investigator, would preclude IVT injection in the study eye. 8. Intraocular pressure in either eye ≥25 mmHg on maximal medication. 9. Cataract surgery and laser corneal surgery within 3 months prior to dosing in the study eye and all other intraocular surgeries at any time. 10. Participation in a concurrent interventional study within 30 days prior to dosing. Key Stratum II Inclusion Criteria: 1. History of diabetes mellitus (Type 1 or Type 2). 2. Retinal thickening secondary to the edema caused by diabetes mellitus. 3. Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in the study eye at Screening. 4. Standard of care treatment for DME can be withheld for at least 90 days after the subject has enrolled in the study (study eye only). Key Stratum II
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and dose-limiting toxicities (Stratum I) | 6 months post-injection | \- To determine the safety and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655 in subjects with low vision |
| Pharmacokinetics (Stratum I) | 6 months post-injection | \- To determine the pharmacokinetics (PK) of a single IVT injection of PF-04523655 in subjects with low vision |
| Safety and tolerability (Stratum II) | 30 days after the last injection | \- To evaluate the safety and tolerability of PF-04523655 alone and in combination with ranibizumab in subjects with diabetic macular edema (DME) |
| Efficacy (Stratum II) | 30 days after the last injection | \- To evaluate the ability of PF-04523655 alone and in combination with ranibizumab to improve visual acuity compared to ranibizumab alone in subjects with DME |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II) | 30 days after the last injection | \- To evaluate the anatomical changes in retina and retinal nerve fiber layer (RNFL) morphology following administration of PF-04523655 alone and in combination with ranibizumab compared to ranibizumab alone by fundus photography (FP) and spectral domain optical coherence tomography (SD-OCT) |
Countries
Belgium, Czechia, Germany, Israel, Poland, United Kingdom, United States
Outcome results
None listed