Clinical Trials List
Protocol NumberRTH258-C002
NCT Number(ClinicalTrials.gov Identfier)NCT02434328
2015-10-15 - 2018-04-30
Phase III
Terminated5
ICD-10H35.30
Unspecified macular degeneration
ICD-9362.50
Macular degeneration (senile), unspecified
A Two-Year, Randomized, Double-Masked, Multicenter, Two-Arm Study Comparing the Efficacy and Safety of RTH258 6 mg Versus Aflibercept in Subjects with Neovascular Age-Related Macular Degeneration
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Alcon Research
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Shih-Jen Chen Division of Ophthalmology
- 周昱百 Division of Ophthalmology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 謝易庭 Division of Ophthalmology
- 葉伯廷 Division of Ophthalmology
- CHANG-HAO YANG Division of Ophthalmology
- TSO-TING LAI Division of Ophthalmology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Neovascular Age-Related Macular Degeneration
Objectives
Primary:
To demonstrate that RTH258 6 mg is not inferior toaflibercept 2 mg with respect to the
change in best corrected visual acuity (BCVA) from Baseline to Week 48
Secondary:
To demonstrate that RTH258 6 mg is not inferior to aflibercept 2 mg with respect to the
change in BCVA from Baseline averaged over the period Week 36 to Week 48
To estimate the proportion of q12 (1 injection every 12 weeks) subjects up to Week 48 in the
RTH258 6 mg treatment arm
To estimate the predictive value of the first q12 cycle for maintenance of q12 treatment up
to Week 48 in the RTH258 6 mg treatment arm
To evaluate the efficacy of RTH258 6 mg relative to aflibercept 2 mg over the time period
up to Week 96 by assessing changes in:
o BCVA
o Anatomical parameters of disease activity including central subfield thickness (CSFT)
and CNV area
o Presence of “q8 treatment need”, including assessment of q12 status for patients in the
RTH258 6 mg treatment arm
To assess visual function-related, subject reported, outcomes following treatment with
RTH258 6 mg relative to aflibercept 2 mg
To assess the safety and tolerability of RTH258 6 mg relative to aflibercept 2 mg
Test Drug
RTH258
Active Ingredient
RTH258 (Humanized monoclonal scFv antibody fragment )
Dosage Form
Solution for intravitreal injection
Dosage
6/50
Endpoints
1. Primary endpoint(s):
Primary Efficacy Endpoint:
Change in BCVA from Baseline to Week 48
2. Secondary endpoints:
Key Secondary Efficacy Endpoints
Average change in BCVA from Baseline over the period Week 36 through Week 48. For
each subject, this endpoint is defined as the average of the changes from Baseline to Weeks
36, 40, 44 and 48.
q12 treatment status at Week 48 (for subjects randomized to RTH258 6 mg only)
q12 treatment status at Week 48 with no q8 need during the 1st q12 cycle (at Week 16,
Week 20) (for subjects randomized to RTH258 6 mg only)
Primary Efficacy Endpoint:
Change in BCVA from Baseline to Week 48
2. Secondary endpoints:
Key Secondary Efficacy Endpoints
Average change in BCVA from Baseline over the period Week 36 through Week 48. For
each subject, this endpoint is defined as the average of the changes from Baseline to Weeks
36, 40, 44 and 48.
q12 treatment status at Week 48 (for subjects randomized to RTH258 6 mg only)
q12 treatment status at Week 48 with no q8 need during the 1st q12 cycle (at Week 16,
Week 20) (for subjects randomized to RTH258 6 mg only)
Inclution Criteria
Inclusion criteria:
1. Subjects must give written informed consent before any study level related procedures are
performed
2. Subjects must be 50 years of age or older at Screening
3. Active CNV lesions secondary to AMD that affect the central subfield (including retinal
angiomatous proliferation [RAP] lesions with a CNV component) in the study eye at Screening
and confirmed by the Central Reading Center (CRC)
4. Total area of CNV (including both classic and occult components) must comprise > 50% of the
total lesion area in the study eye at Screening and confirmed by the CRC
5. Intra and/or subretinal fluid affecting the central subfield of the study eye at Screening and
confirmed by the CRC
6. BCVA between 78 and 23 letters, inclusive, in the study eye at Baseline using Early Treatment
Diabetic Retinopathy Study (ETDRS) testing
1. Subjects must give written informed consent before any study level related procedures are
performed
2. Subjects must be 50 years of age or older at Screening
3. Active CNV lesions secondary to AMD that affect the central subfield (including retinal
angiomatous proliferation [RAP] lesions with a CNV component) in the study eye at Screening
and confirmed by the Central Reading Center (CRC)
4. Total area of CNV (including both classic and occult components) must comprise > 50% of the
total lesion area in the study eye at Screening and confirmed by the CRC
5. Intra and/or subretinal fluid affecting the central subfield of the study eye at Screening and
confirmed by the CRC
6. BCVA between 78 and 23 letters, inclusive, in the study eye at Baseline using Early Treatment
Diabetic Retinopathy Study (ETDRS) testing
Exclusion Criteria
Exclusion criteria:
1. Any active intraocular or periocular infection or active intraocular inflammation(eg,infectious
conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at
Baseline
2. Central subfield of the study eye affected by fibrosis or geographic atrophy assessed by color
fundus photography at Screening and confirmed by the CRC
3. Total area of fibrosis ≥ 50% of the total lesion in the study eye at Screening and confirmed by
the CRC
4. Subretinal blood affecting the foveal center point and/or ≥ 50% of the lesion of the study eye at
Screening and confirmed by the CRC
5. Subject has received any approved or investigational treatment for neovascular AMD (other
than vitamin supplements) in the study eye at any time
6. Any history or evidence of a concurrent intraocular condition in the study eye, including retinal
diseases other than neovascular AMD, that, in the judgment of the Investigator, could require
medical or surgical intervention during the course of the study to prevent or treat visual loss that
might result from that condition, or that limits the potential to gain visual acuity upon treatment
with the investigational product.
7. Retinal pigment epithelium (RPE) rip/tear in the study eye at Screening
8. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks
prior to Baseline
9. History or evidence of the following in the study eye:
intraocular or refractive surgery within the 90 day period prior to Baseline
previous penetrating keratoplasty or vitrectomy
previous panretinal photocoagulation
previous submacular surgery, other surgical intervention or laser treatment for AMD
10. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on
medication or according to Investigator’s judgment at Screening
11. Aphakia and/or absence of the posterior capsule in the study eye at Screening
12. Intra- or periocular use of corticosteroids in the study eye during the 6 month period prior to
Baseline
13. Use of topical ocular corticosteroids in the study eye for 60 or more consecutive days within the
90 day period prior to Baseline
14. Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to
Baseline, with the exception of low stable doses of corticosteroids (defined as ≤ 10 mg
prednisolone or equivalent dose used for 90 days or more prior to Baseline). Inhaled, nasal or
dermal steroids are also permitted
15. Previous therapeutic radiation near the region of the study eye
16. Treatment with aflibercept (EYLEA® ), bevacizumab (AVASTIN® ) or pegaptanib
(MACUGEN® ) within the 4 week period prior to Baseline, or with Ranibizumab, 0.5 mg
(LUCENTIS® ) within the 2 week period prior to Baseline in the nonstudy eye
17. History of a medical condition (disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding) that, in the judgment of the Investigator, would preclude scheduled
study visits, completion of the study, or a safe administration of investigational product
18. History of hypersensitivity to any component of the test article, control article, or clinically
relevant sensitivity to fluorescein dye, as assessed by the Investigator
19. 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 pregnancy test.
20. Women of child-bearing potential, defined as all women less than 1 year postmenopausal or less
than 6 weeks since sterilization (further definition can be found in Section 12.7) at Baseline,
unless they are using highly effective methods of contraception during dosing of study treatment.
Effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject).
Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and
withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy)
or tubal ligation at least 6 weeks before Baseline. In case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by follow up hormone level
assessment
Male sterilization (at least 6 months prior to Baseline). For female subjects in the study, the
vasectomized male partner should be the sole partner for that subject
Use of oral, injected or implanted hormonal methods of contraception or other forms of
hormonal contraception that have comparable efficacy (failure rate < 1%), for example
hormone vaginal ring or transdermal hormone contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
21. Participation in an investigational drug, biologic, or device study within 30 days or the duration
of 5 half-lives of the investigational product (whichever is longer) prior to Baseline Note:
observational clinical studies solely involving over-the-counter vitamins, supplements, or diets
are not exclusionary
22. Systemic anti-vascular endothelial growth factor (VEGF) therapy within the 90 day period prior
to Baseline
23. Stroke or myocardial infarction in the 6 month period prior to Baseline
24. Uncontrolled blood pressure defined as a systolic value ≥ 160 mmHg or diastolic value ≥ 100
mmHg at Screening
In cases where both eyes are eligible, the eye with the worse BCVA will be selected as the study
eye. If both eyes have the same BCVA, it is recommended to select the right eye as the study eye.
1. Any active intraocular or periocular infection or active intraocular inflammation(eg,infectious
conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at
Baseline
2. Central subfield of the study eye affected by fibrosis or geographic atrophy assessed by color
fundus photography at Screening and confirmed by the CRC
3. Total area of fibrosis ≥ 50% of the total lesion in the study eye at Screening and confirmed by
the CRC
4. Subretinal blood affecting the foveal center point and/or ≥ 50% of the lesion of the study eye at
Screening and confirmed by the CRC
5. Subject has received any approved or investigational treatment for neovascular AMD (other
than vitamin supplements) in the study eye at any time
6. Any history or evidence of a concurrent intraocular condition in the study eye, including retinal
diseases other than neovascular AMD, that, in the judgment of the Investigator, could require
medical or surgical intervention during the course of the study to prevent or treat visual loss that
might result from that condition, or that limits the potential to gain visual acuity upon treatment
with the investigational product.
7. Retinal pigment epithelium (RPE) rip/tear in the study eye at Screening
8. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks
prior to Baseline
9. History or evidence of the following in the study eye:
intraocular or refractive surgery within the 90 day period prior to Baseline
previous penetrating keratoplasty or vitrectomy
previous panretinal photocoagulation
previous submacular surgery, other surgical intervention or laser treatment for AMD
10. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on
medication or according to Investigator’s judgment at Screening
11. Aphakia and/or absence of the posterior capsule in the study eye at Screening
12. Intra- or periocular use of corticosteroids in the study eye during the 6 month period prior to
Baseline
13. Use of topical ocular corticosteroids in the study eye for 60 or more consecutive days within the
90 day period prior to Baseline
14. Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to
Baseline, with the exception of low stable doses of corticosteroids (defined as ≤ 10 mg
prednisolone or equivalent dose used for 90 days or more prior to Baseline). Inhaled, nasal or
dermal steroids are also permitted
15. Previous therapeutic radiation near the region of the study eye
16. Treatment with aflibercept (EYLEA® ), bevacizumab (AVASTIN® ) or pegaptanib
(MACUGEN® ) within the 4 week period prior to Baseline, or with Ranibizumab, 0.5 mg
(LUCENTIS® ) within the 2 week period prior to Baseline in the nonstudy eye
17. History of a medical condition (disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding) that, in the judgment of the Investigator, would preclude scheduled
study visits, completion of the study, or a safe administration of investigational product
18. History of hypersensitivity to any component of the test article, control article, or clinically
relevant sensitivity to fluorescein dye, as assessed by the Investigator
19. 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 pregnancy test.
20. Women of child-bearing potential, defined as all women less than 1 year postmenopausal or less
than 6 weeks since sterilization (further definition can be found in Section 12.7) at Baseline,
unless they are using highly effective methods of contraception during dosing of study treatment.
Effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject).
Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and
withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy)
or tubal ligation at least 6 weeks before Baseline. In case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by follow up hormone level
assessment
Male sterilization (at least 6 months prior to Baseline). For female subjects in the study, the
vasectomized male partner should be the sole partner for that subject
Use of oral, injected or implanted hormonal methods of contraception or other forms of
hormonal contraception that have comparable efficacy (failure rate < 1%), for example
hormone vaginal ring or transdermal hormone contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
21. Participation in an investigational drug, biologic, or device study within 30 days or the duration
of 5 half-lives of the investigational product (whichever is longer) prior to Baseline Note:
observational clinical studies solely involving over-the-counter vitamins, supplements, or diets
are not exclusionary
22. Systemic anti-vascular endothelial growth factor (VEGF) therapy within the 90 day period prior
to Baseline
23. Stroke or myocardial infarction in the 6 month period prior to Baseline
24. Uncontrolled blood pressure defined as a systolic value ≥ 160 mmHg or diastolic value ≥ 100
mmHg at Screening
In cases where both eyes are eligible, the eye with the worse BCVA will be selected as the study
eye. If both eyes have the same BCVA, it is recommended to select the right eye as the study eye.
The Estimated Number of Participants
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Taiwan
30 participants
-
Global
660 participants
