Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02259088 | A 12-month, Randomized, Efficacy and Safety Study of 0.5 mg Ranibizumab vs Laser in Chinese Diabetic Macular Edema (DME) Patients | PHASE3 | COMPLETED | 384 | — | — | Nov 5, 2014 | Jan 17, 2017 | Feb 1, 2019 | 28 | China |
| NCT01171976 | Efficacy and Safety of Ranibizumab in Two "Treat and Extend" Treatment Algorithms Versus Ranibizumab As Needed in Patients With Macular Edema and Visual Impairment Secondary to Diabetes Mellitus | PHASE3 | COMPLETED | 373 | — | — | Sep 1, 2010 | Apr 1, 2013 | Sep 15, 2014 | 68 | Belgium, Czechia +11 |
| NCT01135914 | Safety, Efficacy and Cost-efficacy of Ranibizumab (Monotherapy or Combination With Laser) in the Treatment of Diabetic Macular Edema (DME) | PHASE3 | COMPLETED | 241 | — | — | Jul 1, 2010 | Mar 1, 2013 | Oct 23, 2014 | 20 | Canada |
| NCT00989989 | Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema | PHASE3 | COMPLETED | 396 | — | — | Sep 1, 2009 | Aug 1, 2011 | Oct 18, 2012 | 35 | China, Hong Kong +4 |
| NCT00687804 | A 12 Month Core Study to Assess the Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema and a 24 Month Open-label Extension Study | PHASE3 | COMPLETED | 345 | — | — | May 1, 2008 | Jan 1, 2012 | Apr 1, 2013 | 13 | Australia, Belgium +11 |
| NCT00284050 | Safety and Efficacy of Ranibizumab in Diabetic Macular Edema With Center Involvement | PHASE2 | COMPLETED | 151 | — | — | Oct 1, 2005 | Jun 1, 2008 | Feb 24, 2011 | 1 | Switzerland |
Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged \[(Month1+Month2+...+Month12)/12\], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement.
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. Additional information about adverse events can be found in the Adverse Event section.
Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. Additional information about adverse events can be found in the Adverse Event section.
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters as described in the Study Operations Manual.
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters as described in the Study Operations Manual.
| Arm | Type | Description |
|---|---|---|
| Ranibizumab (RFB002) | EXPERIMENTAL | 3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser |
| Laser | ACTIVE_COMPARATOR | Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections |
| TE Ranibizumab 0.5 mg and Laser | EXPERIMENTAL | On Day 1, all patients received an intravitreal injection with 0.5 mg ranibizumab and subsequently entered Phase A which comprised of monthly injections. Laser therapy was applied at Day 1. It could then be re-administered according to ETDRS criteria at any visit with 0.5 mg ranibizumab treatment if deemed necessary by the Treating Investigator with a minimal treatment interval between laser treatments of 3 months. Laser therapy was administered ≥ 30 minutes prior to the ranibizumab injection. |
| TE Ranibizumab 0.5 mg alone | EXPERIMENTAL | Patients received ranibizumab intravitreal injection therapy only. |
| PRN Ranibizumab 0.5 mg | ACTIVE_COMPARATOR | Patients received ranibizumab intravitreal injection therapy as needed according to signs and symptoms of disease. |
| Combination Therapy | EXPERIMENTAL | Participants received ranibizumab intravitreal injection and laser photocoagulation treatments |
| Ranibizumab Monotherapy | EXPERIMENTAL | Participants received ranibizumab intravitreal injection therapy only |
| Laser Monotherapy | ACTIVE_COMPARATOR | Participants received Laser photocoagulation therapy only |
| Adjunctive treatment | EXPERIMENTAL | Adjunctive administration of ranibizumab 0.5 mg intravitreal injections and active laser. |
| Monotherapy treatment | EXPERIMENTAL | Monotherapy ranibizumab 0.5 mg intravitreal injections plus sham laser. |
| Laser control | ACTIVE_COMPARATOR | Active laser treatment plus sham intravitreal injections. |
| Ranibizumab 0.5 mg | EXPERIMENTAL | Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met: Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA \> 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits. Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes. In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy. |
| Ranibizumab 0.5 mg + laser | EXPERIMENTAL | Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met: Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA \> 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits. Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes. In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy. |
| Ranibizumab 0.3 mg | EXPERIMENTAL | Participants received monthly intravitreal injections with 0.3 mg ranibizumab (6 mg/ml) for up to 12 months. At each monthly visit from month 1 and onwards, the evaluating physician decided whether an increase in the dose to 0.6 mg was needed according to set criteria. If the dose was increased, all subsequent administrations were of the higher dose unless treatment had been withheld for more than 45 days (for any reason), in which case injections restarted with the initial dose. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. |
| Sham injection | SHAM_COMPARATOR | Participants in the control group received 12 monthly sham intravitreal injections. The evaluation was performed using the same criteria for dose doubling as in active treatment groups. The injection was a mimicked by an empty syringe without a needle. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. |
| Name | Type | Description |
|---|---|---|
| Ranibizumab (RFB002) | DRUG | Ranibizumab 0.5 mg/0.05 mL for intravitreal injection |
| Laser | PROCEDURE | Laser photocoagulation according to Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines |
| Sham injection | DRUG | Imitation of an intravitreal injection consisting of an empty vial and an injection syringe without a needle |
| Sham laser | PROCEDURE | Imitation of an active laser |
| Ranibizumab | DRUG | Ranibizumab (Lucentis®) was supplied in vials containing a dose of 0.5 mg/0.05 mL in an aqueous solution (pH 5.5) with histidine, trehalose, and polysorbate 20. |
| Laser photocoagulation | PROCEDURE | Active laser treatment administered at day 1. Subsequent laser treatments administered if needed at intervals no shorter than 3 months from previous laser treatment. |
| Sham ranibizumab | DRUG | Sham intravitreal injections to ranibizumab at day 1, month 1 and month 2. Intravitreal injections re-initiated if needed. |
| Sham laser photocoagulation | PROCEDURE | Sham laser treatment administered at day 1. |
| Sham to ranibizumab | DRUG | Sham to ranibizumab administered as an intravitreal injection. |
| Ranibizumab 0.3 mg | DRUG | 6 mg/ml ranibizumab solution for intravitreal injection |
| Ranibizumab 0.5 mg | DRUG | 10 mg/ml ranibizumab solution for intravitreal injection |
Key Inclusion Criteria: * Male or female Chinese patients ≥ 18 years of age with diabetes mellitus and with HbA1c ≤10.0% * Stable medication for diabetes within 3 months prior to Visit 1 * Visual impairment due to DME with BCVA score between 78 and 39 letters as measured by ETDRS-like charts at 4 m...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| EyePoint, Inc. | EYPT | 2 | PHASE3 | EYP-1901, Aflibercept |
| Regeneron Pharmaceuticals, Inc. | REGN | 1 | PHASE3 | Aflibercept |
| Oculis Holding AG | OCS | 2 | PHASE3 | Dexamethasone, Vehicle |
| AbbVie, Inc. | ABBV | 3 | PHASE2 | ABBV-RGX-314 Dose 1, Steroid, Aflibercept |
| Outlook Therapeutics, Inc. | OTLK | 1 | PHASE3 | bevacizumab |
| 4D Molecular Therapeutics, Inc. | FDMT | 1 | PHASE2 | 4D-150 IVT, Aflibercept IVT |
| Alvotech | ALVO | 1 | PHASE3 | AVT29, Eylea HD |
| Kiora Pharmaceuticals, Inc. | KPRX | 1 | PHASE2 | KIO-104 |
| REGENXBIO, Inc. | RGNX | 1 | PHASE2 | RGX-314 Dose 1, RGX-314 Dose 2, Aflibercept |
| Ocugen Inc | OCGN | 1 | PHASE1 | OCU200 |
| Adverum Biotechnologies, Inc. | ADVM | 1 | — | ADVM-022 |