Efficacy and safety of two different treatment patterns of ranibizumab in patients with wet AMD

• Register: EUCTR
• Last refreshed on: 20 June 2016
• Main ID: EUCTR2011-004959-39-IE
• Date of registration: 07/03/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Efficacy and safety of two different treatment patterns of ranibizumab in patients with wet AMD
• Scientific title: A 24-month, phase IIIb, randomized, double-masked, multicenter study assessing the efficacy and safety of two treatment regimens of 0.5 mg ranibizumab intravitreal injections guided by functional and/or anatomical criteria, in patients with neovascular age-related macular degeneration (OCTAVE) - OCTAVE
• Date of first enrolment: 05/06/2013
• Target sample size: 670
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004959-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Lucentis Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Canada, Colombia, Czech Republic, Finland, France, Germany, Greece, Guatemala, Hungary, Ireland, Italy, Lithuania, Mexico, Netherlands, Panama, Portugal, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom, Venezuela, Bolivarian Republic of

Contacts

• Name: Collette Cairnduff
• Affiliation: Novartis Ireland Limited

• Name: Collette Cairnduff
• Affiliation: Novartis Ireland Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria for patient
1. Written informed consent must be obtained before any study-related assessment is performed.
2. Male or female patients, =50 years of age.

Inclusion criteria for study eye
3. Visual impairment predominantly due to neovascular AMD
4. Active, newly diagnosed, angiographically documented CNV (i.e. leakage on fluorescein angiography plus intraretinal, subretinal or sub RPE fluid on OCT) secondary to AMD in an eye previously untreated with verteporfin PDT, external-beam radiation, subfoveal or extrafoveal focal laser photocoagulation, transpupillary thermotherapy, submacular surgery, or any other surgical intervention for wAMD, any anti-VEGF compound or any investigational treatment, intravitreal or subtenon corticosteroid injection (within 90 days prior to screening) or device implantation
5. CNV or sequelae of the CNV (i.e., pigment epithelium detachment, subretinal or sub-RPE hemorrhage, blocked fluorescence, macular edema, or subretinal, sub-RPE or intraretinal fluid) involving the center of the fovea.
6. BCVA score at both Screening and Baseline between 78 and 23 letters inclusive (approximate Snellen equivalent of 20/32 and 20/320) as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at 4 meters.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion criteria:
Exclusion criteria for patient
1. Inability to comply with study or follow-up procedures.
2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
3. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Exclusion criteria for systemic medical history and conditions
4. Any type of systemic disease or its treatment, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
5. Stroke or myocardial infarction less than 3 months prior to Screening.
6. Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value of >100 mm Hg at Screening or Baseline.
7. Known hypersensitivity to ranibizumab or any component of the ranibizumab formulation, or fluorescein.

Exclusion criteria for ocular medical history and conditions
For either eye
8. Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of Screening or Baseline.
9. Uncontrolled glaucoma (intraocular pressure [IOP] =30 mm Hg on medication or according to investigator’s judgment) at the time of Screening or Baseline.
10. Neovascularization of the iris or neovascular glaucoma at the time of Screening or Baseline.
11. Inability to obtain optical coherence tomography (OCT) images of sufficient quality to be analyzed.

For study eye
12. Cataract (if causing significant visual impairment), aphakia, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause than wet AMD (e.g., ocular histoplasmosis, pathologic myopia) at the time of Screening or Baseline.
13. Irreversible structural damage within 0.5 disc diameter of the center of the macula (e.g., vitreomacular traction, epiretinal membrane, scar, laser burn, macular hole) at the time of Screening or Baseline that in the investigator’s opinion could substantially impact visual function improvement with treatment.
14. Atrophy or fibrosis involving the center of the fovea.
15. Total area of fibrosis comprising more than 50% of the lesion area.

Exclusion criteria for prior or current systemic medication
16. Use of other investigational drugs within 30 days or 5 half-lives from Baseline, whichever is longer.
17. Use of any systemic anti-VEGF drugs within 3 months prior to Baseline (e.g., bevacizumab [Avastin®]).
18. Use of systemic corticosteroids for at least 30 consecutive days within 3 months prior to screening.
19. Current or planned use of systemic medications known to be toxic to the lens, retina or
optic nerve, including deferoxamine, chloroquine/ hydroxychloroquine (Plaquenil®), tamoxifen, phenothiazines and ethambutol.
Exclusion criteria for prior or current ocular treatment
For fellow eye
20. Treatment with any anti-angiogenic drugs (including any anti-VEGF agents) within 3 months prior to Baseline in either eye (e.g., bevacizumab [Avastin®]).
For study eye
21. Any intraocular procedure (including Yttrium-Aluminum-Garnet capsu

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Visual impairment due to neovascular AMD
MedDRA version: 16.1 Level: LLT Classification code 10060837 Term: Choroidal neovascularization System Organ Class: 100000004853

Intervention(s)

Trade Name: Lucentis
Product Name: Lucentis
Product Code: RFB002A
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RANIBIZUMAB
CAS Number: 347396-82-1
Current Sponsor code: RFB002
Concentration unit: µl microlitre(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: The primary objective is to evaluate the effectiveness of two treatment regimens by assessing the average BCVA change from Month 4 to Month 12 compared to Month 3 based on both, BCVA stability in each treatment group and comparison of the two treatment groups. For the analysis of these objectives a reference margin of two letters will be applied.
A treatment regimen will be considered a relevant option if stability is achieved and non-inferiority compared to the other group is demonstrated.

Primary end point(s): Average Visual Acuity change from Month 3 to Month 4 through Month 12

Timepoint(s) of evaluation of this end point: Month 3 to Month 12

Secondary Objective: To evaluate the efficacy of the two treatment regimens by assessing
•time course of BCVA from baseline (BL),
•improvement of BCVA =1, =5, =10, and =15 letters from BL, at M12 and 24,
•loss of BCVA <5, <10, and <15 letters from BL, at M12 and 24,
•BCVA =73 letters at M12 and 24,
•average BCVA change from M4 to M24 compared to M3,
•average BCVA change from M1 to M12, and to M24 compared to BL.
To assess treatment exposure and patterns of the two treatment regimens over time based on
•frequency,
•reason,
•compliance
•duration of treatment-free intervals
•duration of active treatment-phases.
To evaluate the retinal anatomy by
•change in central subfield retinal thickness and central subfield volume from BL, over time,
•proportion of patients achieving a dry retina at M12 and M24,
•change in lesion size and morphology at M12 and M24.
To evaluate the change in VFQ-25 composite and subscale scores over time.
To evaluate the safety of ranibizumab over 12 and 24 months.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to Month 12/24
Month 12/24
Month 3 to Month 24
Screening to Month 12/24

Secondary end point(s): Change from Baseline in Visual Acuity (Letters) of the Study Eye over time

Gain of equal or more than 1, 5, 10, or 15 letters in Visual Acuity of the Study Eye from baseline, at Month 12/24

Loss of less than 5, 10, and 15 letters in Visual Acuity in the Study Eye from baseline, at Month 12/24

Visual Acuity of 73 letters or more in the Study Eye at Month 12/24

Average Visual Acuity change from Month 3 to Month 4 through Month 24 in the Study Eye

Average Visual Acuity change from baseline to Month 1 through Month 12/24 in the Study Eye

Change from Baseline in Central Sub-Field Thickness (CSFT) and Central Sub-Field Volume (CSFV) of the Study Eye over time

Dry retina in the Study Eye on OCT at Month 12/24

Change from baseline in lesion size and morphology based on fluorescein angiography at Month 12/24

Treatment patterns over time in both treatment arms

Change from Baseline in the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) scores over time

Frequency and severity of ocular and non-ocular adverse events over time

Secondary ID(s)

2011-004959-39-CZ

CRFB002A2405

Source(s) of Monetary Support

Novartis Pharma Services AG