Efficacy and Safety of Lucentis® Use in Patients With Diabetic Macular Edema Evaluating a Spaced Out Follow-up After Intensive Treatment Phase

Diabetes Clinical Trial

— CONSTELLATION  

Official title:

A 24 Month Open-label, Multicenter, Phase IIIb Study of the Efficacy and Safety of Lucentis® (Ranibizumab 0,5mg) in Diabetic Patients With Visual Impairment Due to Macular Edema Evaluating a Spaced Out Follow-up After Intensive Loading Phase

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02032173
• Other study ID #: CRFB002DFR11
• Status: Terminated
• Phase: Phase 3
• Start date: May 19, 2014
• Est. completion date: April 29, 2015

Study information

• Verified date: September 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: April 29, 2015
• Est. primary completion date: April 29, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Edema
• Macular Degeneration
• Macular Edema

Intervention

Drug:
• Ranibizumab 0.5mg
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)

Locations

Country	Name	City	State
France	Novartis Investigative Site	Bobigny cedex	Seine Saint Denis
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Le Kremlin Bicetre Cedex
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris Cedex 19
France	Novartis Investigative Site	Poitiers

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months	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.	Month 6 and 24
Secondary	Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 11 Months	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%.	Month 11 and 24
Secondary	Visual Acuity: Number of Participants Keeping a BCVA Score Gain =10 Letters	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.	Baseline, Month 3, 6, 8 and 11
Secondary	Visual Acuity: Number of Participants Keeping a BCVA Score Gain =15 Letters	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.	Baseline, Months 3, 6, 8 and 11
Secondary	Visual Acuity: Number of Participants With a BCVA Loss =15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye.	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.	Months 6, 8 and 11
Secondary	Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)	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.	Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
Secondary	Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye	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]).	Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
Secondary	Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) - Rescue Group	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.	Baseline, Months 3, 6, 8 and 11
Secondary	Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye - Rescue Group	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]).	Baseline, Months 3, 6, 8 and 11
Secondary	Evaluation of the Spaced Out Follow-up on Visual Functions and Quality of Life	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.	baseline, months 11, 12 and 24