Macular EdemaPhase 3CONSTELLATIONNCT02032173
Efficacy and Safety of Lucentis® Use in Patients With Diabetic Macular Edema Evaluating a Spaced Out Follow-up After Intensive Treatment Phase
A Phase 3 study testing Ranibizumab 0.5mg in people with Macular Edema and Macular Degeneration, run by Novartis Pharmaceuticals at 10 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Macular Edema, Macular Degeneration, Diabetes
- What is being tested?
- Ranibizumab 0.5mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 10 sitesFrance
- Study dates
- 19 May 2014to 29 Apr 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
Novartis Investigative Site
Bobigny, Seine Saint Denis, 93009
Novartis Investigative Site
Bordeaux, 33000
Novartis Investigative Site
Bordeaux, F-33076
Novartis Investigative Site
Créteil, 94000
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Lyon, 69002
Novartis Investigative Site
Nice, 06000
Novartis Investigative Site
Paris, 75015
Novartis Investigative Site
Paris, 75940
Novartis Investigative Site
Poitiers, 86021
About this study
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
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.
Read the 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.
- Conditions
- Macular Edema, Macular Degeneration, Diabetes
- Being tested
- Ranibizumab 0.5mg
- Keywords
- Ranibizumab, Diabetic Macular Edema
- Medical subject headings
- Macular Edema, Macular Degeneration, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ranibizumab 0.5mgDrug
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
| Study group | Role | What they receive |
|---|---|---|
| Ranibizumab 0.5mg | Experimental | Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) Receives: Drug: Ranibizumab 0.5mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 6 and 24
Secondary outcomes (9)
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%.
Measured: Month 11 and 24
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.
Measured: Baseline, Month 3, 6, 8 and 11
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.
Measured: Baseline, Months 3, 6, 8 and 11
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.
Measured: Months 6, 8 and 11
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.
Measured: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
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]).
Measured: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
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.
Measured: Baseline, Months 3, 6, 8 and 11
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]).
Measured: Baseline, Months 3, 6, 8 and 11
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.
Measured: baseline, months 11, 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study start19 May 2014
- Primary completion29 Apr 2015
- Study completion29 Apr 2015
Why it stopped: Study was prematurely discontinued as it was unethical to continue based on a change in ranibizumab (RFB) marketing authorization.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Macular EdemaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02032173
- Sponsor's protocol ID
- CRFB002DFR11
- Acronym
- CONSTELLATION
- Status last verified
- Sep 2020
- First submitted
- 8 Jan 2014
- Last updated
- 22 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02032173
- Acronym / sponsor ID
- CONSTELLATION / CRFB002DFR11
- Conditions
- Macular Edema, Macular Degeneration, Diabetes
- Keywords
- Ranibizumab, Diabetic Macular Edema
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was prematurely discontinued as it was unethical to continue based on a change in ranibizumab (RFB) marketing authorization.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 19 May 2014 (actual)
- Primary completion
- 29 Apr 2015 (actual)
- Study completion
- 29 Apr 2015 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Posted 22 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ranibizumab 0.5mg | Experimental | Drug: Ranibizumab 0.5mgIntravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ranibizumab 0.5mgIntravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) | Drug | Ranibizumab 0.5mg |
Primary outcome
Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months
Time frame: 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.
9 secondary outcomes
Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 11 Months
Time frame: Month 11 and 24
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters
Time frame: Baseline, Month 3, 6, 8 and 11
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters
Time frame: Baseline, Months 3, 6, 8 and 11
Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye.
Time frame: Months 6, 8 and 11
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Time frame: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Time frame: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) - Rescue Group
Time frame: Baseline, Months 3, 6, 8 and 11
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye - Rescue Group
Time frame: Baseline, Months 3, 6, 8 and 11
Evaluation of the Spaced Out Follow-up on Visual Functions and Quality of Life
Time frame: baseline, months 11, 12 and 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ranibizumab 0.5mg in people with Macular Edema and Macular Degeneration, run by Novartis Pharmaceuticals at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months (time frame: Month 6 and 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.