A Study to Evaluate Efficacy, Safety & Pharmacokinetics o... | NCT04108156

NCT04108156

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PDS Arm	Experimental	Participants randomized to the PDS arm will receive IVT ranibizumab injection Q4W (loading phase) and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.	Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Drug: Ranibizumab refill exchange
Intravitreal Arm	Active Comparator	Participants randomized to the intravitreal arm will receive IVT ranibizumab injection Q4W until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.	Drug: Intravitreal Ranibizumab 0.5 mg Injection Drug: Ranibizumab refill exchange
Substudy: Cohort 1	Experimental	Participants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 milligrams per milliliter [mg/mL]) on Day 1 (or enrollment visit) and then will have two refill-exchanges (ranibizumab 100 mg/mL) Q24W up to 48 weeks.	Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Drug: Ranibizumab refill exchange
Substudy: Cohort 2a	Experimental	Participants who received an updated PDS implant, have < 24 weeks post-re-implantation follow-up and no scheduled refill-exchange visit in the main study, will undergo two refill-exchange procedures (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PDS Implant Pre-Filled with 100 mg/mL Ranibizumab	Drug	Will be administered as per the schedule described in individual arm.	PDS Arm Substudy: Cohort 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured Using the ETDRS Chart in the Efficacy Population Using a Treatment Policy Strategy for all Intercurrent Events	BCVA = Best-Corrected Visual Acuity ETDRS = Early Treatment Diabetic Retinopathy Study A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.	Baseline to Week 64
Substudy: Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of Ocular and Systemic AEs		Baseline to Week 72
Substudy: Number of Participants With Adverse Events of Special Interests (AESIs) and Severity of AESIs		Baseline to Week 72
Substudy: Duration of AESIs		Baseline to Week 72
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period		Up to Day 37 post re-implantation
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period		> 37 days post-implantation (up to approximately 72 weeks)
Substudy: Duration of Ocular AESIs During the Post-operative Period		Up to Day 37 post re-implantation
Substudy: Duration of Ocular AESIs During the Follow-up Period		> 37 days post-implantation (up to approximately 72 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured With Use of the ETDRS Chart in the Modified Intent-to-treat (mITT) Population Using a Treatment Policy Strategy for All Intercurrent Events	ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale	Baseline to Week 64
Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured With Use of the ETDRS Chart in the mITT Population Using a Hypothetical Strategy for All Intercurrent Events

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years at time of signing informed consent form (ICF)
Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
Glycated haemoglobin (HbA1c) level of ≤10% within 2 months prior to screening or at screening

Study eye

Macular thickening secondary to DME involving the center of the fovea with CST ≥325 micrometer (µm) on SD-OCT at screening
BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)

Exclusion Criteria:

High-risk PDR
Active intraocular inflammation (grade trace or above)
Suspected or active ocular or periocular infection of either eye
Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
Uncontrolled blood pressure

Substudy:

Inclusion Criteria:

Having experienced a septum dislodgement in the original implant while in the main study or after exiting the main study
Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by central reading center

Exclusion Criteria (Cohort 1 Only):

Recent history (in the last 3 months prior to enrollment) of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the participant at high risk for treatment complications
Active cancer within the last 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer
Current systemic treatment for a confirmed active systemic infection
Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals or enrollment in Study GR40550) within 6 months prior to enrollment
Use of antimitotic or antimetabolite therapy within 30 days

Ocular Exclusion Criteria for Study Eye:

Any ocular condition that may render the participant at high risk for surgical or treatment complications
Intraocular surgery (including cataract surgery) within 1 month preceding the enrollment visit
Any use of medicated intraocular implants (other than the PDS implant), at any time prior to enrollment
History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
Any concurrent ocular condition that would require surgical intervention during the study to prevent or treat visual loss
Concurrent conjunctival, tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the refill-exchange procedure of the PDS implant
Ongoing ocular complications that might affect participant safety Ocular Exclusion Criteria for Either Eye
Suspected or active ocular or periocular infection (e.g., infectious conjunctivitis or endophthalmitis)
Any history of uveitis
Active blepharitis

Facility	Status	City	State	ZIP	Country	Contacts
Barnet Dulaney Perkins Eye Center		Mesa	Arizona	85206	United States
Retinal Consultants of Arizona;Opthalmology

PubMed Identifier	Type	Citation	Retractions
40048197	Derived	Khanani AM, Campochiaro PA, Graff JM, Marcus DM, Miller D, Mittra RA, Regillo C, Sheth VS, Bobbala A, Gune S, Lin S, Quezada-Ruiz C, Malhotra V. Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema: The Pagoda Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):326-335. doi: 10.1001/jamaophthalmol.2025.0006.
37585454

ID	Term
D000069579	Ranibizumab
D007267	Injections

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics