CONSTELLATION: Efficacy and Safety of Lucentis® Use in Patients With Diabetic Macular Edema Evaluating a Spaced Out Follow-up After Intensive Treatment Phase
Study Details
Study Description
Brief Summary
The study was designed to assess the efficacy and safety of Lucentis® (ranibizumab 0.5 mg) in diabetic patients presenting with reduced visual acuity due to diabetic macular edema and evaluating spacing out of follow-up after initial intensive treatment phase.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This was a multicenteric, open-label, phase IIIb study, which comprised of 2 groups: the Main Group and the Rescue Group.
Patient's eligibility was assessed during a screening visit (Visit 1) which took place 14 days maximum before treatment initiation (Visit 2 [Day 0]). All patients were initially included in the Main Group and were to receive an initial loading treatment (6 injections during the intensive treatment phase i.e. every month from Day 0 to Month 5, followed by 2 additional injections at Months 8 and 11). Patients were to be followed-up every 3 months for 18 months (spaced-out follow-up period). Their visual acuity was to be checked at each study visit (Months 3, 6, 8, 11, 14, 17, 20, and 23) to assess their response to treatment. Patients who responded to treatment were maintained in the Main Group. Patients who did not meet pre defined criteria were moved to the Rescue Group and treated at the investigator's discretion.
The trial was terminated before any patient reached month 12.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ranibizumab 0.5mg Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
Drug: Ranibizumab 0.5mg
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months [Month 6 and 24]
Best-Corrected Visual Acuity (BCVA) letters were 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 6 months minus BCVA score at 24 months ≤4 letters) were reported.
Secondary Outcome Measures
- Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 11 Months [Month 11 and 24]
Best-Corrected Visual Acuity (BCVA) letters were 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 11 months minus BCVA score at 24 months ≤4 letters) was calculated as well as its confidence interval at 95%.
- Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters [Baseline, Month 3, 6, 8 and 11]
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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥10 letters gains in BCVA (compared to the baseline BCVA [Day 0]) value for each visit from Month 3 onwards were reported.
- Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters [Baseline, Months 3, 6, 8 and 11]
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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥15 letters gains in BCVA (compared to the baseline BCVA [Day 0]) value for each visit from Month 3 onwards were reported.
- Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye. [Months 6, 8 and 11]
Best-Corrected Visual Acuity (BCVA) letters were 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. Number of participants presenting with a ≥15 letter loss in BCVA (compared to the value observed at 6 months) and leading to a treatment change (Rescue Group) for month 8 and 11 were analyzed.
- Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) [Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11]
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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value [Day 0] over a period of 24 months for patients in the Main Group.
- Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye [Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11]
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) was measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log[CRT/200]).
- Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) - Rescue Group [Baseline, Months 3, 6, 8 and 11]
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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value [Day 0] over a period of 24 months for patients in the Rescue Group.
- Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye - Rescue Group [Baseline, Months 3, 6, 8 and 11]
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log[CRT/200]).
- Evaluation of the Spaced Out Follow-up on Visual Functions and Quality of Life [baseline, months 11, 12 and 24]
The global score obtained on the Visual Function Questionnaire 25 (VFQ 25) was compared from baseline to months 11 and 24 for the Main group and from baseline to months 12 and 24 for the Rescue group.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Type I or type II diabetes with HbA1c≤10%
-
Visual impairment due to a diabetic macular edema
-
Stable antidiabetic treatment (since more than 3 months) or hygiene-dietary
Exclusion Criteria:
-
Inflammation or infection in one eye
-
Women of childbearing potential without an efficient contraception, pregnant or breastfeeding
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Bobigny cedex | Seine Saint Denis | France | 93009 |
| 2 | Novartis Investigative Site | Bordeaux Cedex | France | F-33076 | |
| 3 | Novartis Investigative Site | Bordeaux | France | 33000 | |
| 4 | Novartis Investigative Site | Creteil | France | 94000 | |
| 5 | Novartis Investigative Site | Le Kremlin Bicetre Cedex | France | 94275 | |
| 6 | Novartis Investigative Site | Lyon | France | 69002 | |
| 7 | Novartis Investigative Site | Nice | France | 06000 | |
| 8 | Novartis Investigative Site | Paris Cedex 19 | France | 75940 | |
| 9 | Novartis Investigative Site | Paris | France | 75015 | |
| 10 | Novartis Investigative Site | Poitiers | France | 86021 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRFB002DFR11
Study Results
Participant Flow
| Recruitment Details | Participants were recruited from 10 centers across France. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Period Title: Overall Study | |
| STARTED | 31 |
| Included Population - Main Group | 31 |
| Rescue Group | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 31 |
Baseline Characteristics
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Overall Participants | 31 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
64.7
(7.08)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
10
32.3%
|
| Male |
21
67.7%
|
Outcome Measures
| Title | Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months |
|---|---|
| Description | Best-Corrected Visual Acuity (BCVA) letters were 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 6 months minus BCVA score at 24 months ≤4 letters) were reported. |
| Time Frame | Month 6 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12 |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 0 |
| Title | Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 11 Months |
|---|---|
| Description | Best-Corrected Visual Acuity (BCVA) letters were 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 11 months minus BCVA score at 24 months ≤4 letters) was calculated as well as its confidence interval at 95%. |
| Time Frame | Month 11 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12 |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 0 |
| Title | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters |
|---|---|
| Description | 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥10 letters gains in BCVA (compared to the baseline BCVA [Day 0]) value for each visit from Month 3 onwards were reported. |
| Time Frame | Baseline, Month 3, 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population with evaluable patients at specific time points. |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 21 |
| Month 3 |
8
25.8%
|
| Month 6 |
4
12.9%
|
| Month 8 |
3
9.7%
|
| Month 11 |
1
3.2%
|
| Title | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters |
|---|---|
| Description | 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥15 letters gains in BCVA (compared to the baseline BCVA [Day 0]) value for each visit from Month 3 onwards were reported. |
| Time Frame | Baseline, Months 3, 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population with evaluable patients at specific time points. |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 21 |
| Month 3 |
4
12.9%
|
| Month 6 |
3
9.7%
|
| Month 8 |
1
3.2%
|
| Month 11 |
0
0%
|
| Title | Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye. |
|---|---|
| Description | Best-Corrected Visual Acuity (BCVA) letters were 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. Number of participants presenting with a ≥15 letter loss in BCVA (compared to the value observed at 6 months) and leading to a treatment change (Rescue Group) for month 8 and 11 were analyzed. |
| Time Frame | Months 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population with evaluable patients at specific time points. |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 5 |
| Month 6 to Month 8 |
0
0%
|
| Month 6 to Month 11 |
0
0%
|
| Title | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) |
|---|---|
| Description | 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value [Day 0] over a period of 24 months for patients in the Main Group. |
| Time Frame | Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population with evaluable patients at specific time points. |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 31 |
| Month 1 |
5.45
(6.444)
|
| Month 2 |
5.81
(7.328)
|
| Month 3 |
8.05
(6.704)
|
| Month 4 |
9.94
(5.805)
|
| Month 5 |
9.88
(5.290)
|
| Month 6 |
11.00
(8.485)
|
| Month 8 |
10.40
(5.413)
|
| Month 11 |
10.00
(NA)
|
| Title | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye |
|---|---|
| Description | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) was measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log[CRT/200]). |
| Time Frame | Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12 |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 31 |
| Month 1 |
-0.10
(0.117)
|
| Month 2 |
-0.12
(0.122)
|
| Month 3 |
-0.13
(0.123)
|
| Month 4 |
-0.13
(0.104)
|
| Month 5 |
-0.16
(0.096)
|
| Month 6 |
-0.15
(0.120)
|
| Month 8 |
-0.12
(0.062)
|
| Month 11 |
-0.13
(NA)
|
| Title | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) - Rescue Group |
|---|---|
| Description | 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 change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value [Day 0] over a period of 24 months for patients in the Rescue Group. |
| Time Frame | Baseline, Months 3, 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population for subjects entering Rescue Group: No subjects provided evaluable data after switching to the Rescue Group |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 0 |
| Title | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye - Rescue Group |
|---|---|
| Description | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log[CRT/200]). |
| Time Frame | Baseline, Months 3, 6, 8 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population for subjects entering Rescue Group: No subjects provided evaluable data after switching to the Rescue Group |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 0 |
| Title | Evaluation of the Spaced Out Follow-up on Visual Functions and Quality of Life |
|---|---|
| Description | The global score obtained on the Visual Function Questionnaire 25 (VFQ 25) was compared from baseline to months 11 and 24 for the Main group and from baseline to months 12 and 24 for the Rescue group. |
| Time Frame | baseline, months 11, 12 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12 |
| Arm/Group Title | Ranibizumab |
|---|---|
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Ranibizumab | |
| Arm/Group Description | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) | |
All Cause Mortality |
||
| Ranibizumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/31 (0%) | |
Serious Adverse Events |
||
| Ranibizumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/31 (6.5%) | |
| Metabolism and nutrition disorders | ||
| Diabetes mellitus inadequate control | 1/31 (3.2%) | |
| Musculoskeletal and connective tissue disorders | ||
| Osteonecrosis | 1/31 (3.2%) | |
Other (Not Including Serious) Adverse Events |
||
| Ranibizumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 12/31 (38.7%) | |
| Cardiac disorders | ||
| Coronary artery stenosis | 1/31 (3.2%) | |
| Eye disorders | ||
| Eye allergy (Both eyes) | 1/31 (3.2%) | |
| Halo vision (Study eye) | 1/31 (3.2%) | |
| Macular oedema (Contralateral eye) | 1/31 (3.2%) | |
| Posterior capsule opacification (Contralateral eye) | 1/31 (3.2%) | |
| Vitreous haemorrhage (Study eye) | 1/31 (3.2%) | |
| Gastrointestinal disorders | ||
| Abdominal pain upper | 1/31 (3.2%) | |
| General disorders | ||
| Chills | 1/31 (3.2%) | |
| Oedema peripheral | 1/31 (3.2%) | |
| Pyrexia | 1/31 (3.2%) | |
| Infections and infestations | ||
| Conjunctivitis (Both eyes) | 1/31 (3.2%) | |
| Conjunctivitis viral (Study eye) | 1/31 (3.2%) | |
| Gastroenteritis | 3/31 (9.7%) | |
| Nasopharyngitis | 1/31 (3.2%) | |
| Injury, poisoning and procedural complications | ||
| Wound | 1/31 (3.2%) | |
| Nervous system disorders | ||
| Paraesthesia | 1/31 (3.2%) | |
| Renal and urinary disorders | ||
| Microalbuminuria | 1/31 (3.2%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/31 (3.2%) | |
| Epistaxis | 1/31 (3.2%) | |
| Vascular disorders | ||
| Peripheral arterial occlusive disease | 1/31 (3.2%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-1873 |
- CRFB002DFR11