TLC399 (ProDex) in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)

Sponsor
Taiwan Liposome Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03093701
Collaborator
(none)
31
20
4
22.1
1.6
0.1

Study Details

Study Description

Brief Summary

Randomized, double-masked trial designed to investigate the use of TLC399 (ProDex) in subjects with macular edema due to CRVO or BRVO.

Condition or Disease Intervention/Treatment Phase
  • Drug: TLC399 (ProDex)
Phase 2

Detailed Description

Part 1 is a randomized, double-maskedtrial trial designed to investigate the use of TLC399 in subjects with macular edema due to CRVO or BRVO. Three different dose strengths will be evaluated.

Part 2 is a randomized, double-masked study designed to evaluate 2 doses of TLC399 in subjects with macular edema due to CRVO or BRVO. Subjects will be randomized 1:1 to receive two different dose strenghs of investigational product.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
TLC399 (ProDex) in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)
Actual Study Start Date :
Apr 1, 2017
Actual Primary Completion Date :
Feb 4, 2019
Actual Study Completion Date :
Feb 4, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 1

TLC399 (ProDex) 0.36mg DSP with 100 mM PL

Drug: TLC399 (ProDex)
2-vial system: TLC399-DSP and TLC399-Lipid
Other Names:
  • TLC399
  • Experimental: Group 2

    TLC399 (ProDex) 0.6 mg DSP with 100 mM PL

    Drug: TLC399 (ProDex)
    2-vial system: TLC399-DSP and TLC399-Lipid
    Other Names:
  • TLC399
  • Experimental: Group 3

    TLC399 (ProDex) 0.6 mg DSP with 50 mM PL

    Drug: TLC399 (ProDex)
    2-vial system: TLC399-DSP and TLC399-Lipid
    Other Names:
  • TLC399
  • Experimental: Group 4

    TLC399 (ProDex) 0.84 mg DSP with 50 mM PL

    Drug: TLC399 (ProDex)
    2-vial system: TLC399-DSP and TLC399-Lipid
    Other Names:
  • TLC399
  • Outcome Measures

    Primary Outcome Measures

    1. Proportion of Subjects With BCVA Gain of 15 or More Letters From Baseline in the Study Eye [6 months after dosing]

      Proportion of subjects with BCVA gain of 15 or more letters from baseline in the study eye. Patients who received rescue medication/procedures within 6 months after the study treatment was initiated were considered failure to achieve a gain of at least 15 BCVA letters.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. male or female, at least 18 years of age

    2. macular edema due to CRVO or BRVO

    3. best-corrected visual acuity (BCVA) score of 20/40 to 20/400

    4. mean central subfield thickness (CST) ≥350 um

    5. willing and able to comply with the study procedure and sign a written informed consent

    6. agree to use a medically acceptable form of birth control

    Exclusion Criteria:
    1. poorly controlled diabetes

    2. history of significant intraocular pressure (IOP) elevation to steroid treatment

    3. history of ocular hypertension and glaucoma

    4. cataract surgery in the study eye within 3 months, or intraocular surgery within 6 months prior to screening

    5. use of hemodilution for the treatment of RVO

    6. use of IVT ranibizumab or bevacizumab in the study eye within 6 weeks prior to screening; or IVT aflibercept within 8 weeks prior to screening

    7. IVT Ozurdex to the study eye within 6 months prior to screening

    8. prior use of Retisert or Iluvien

    9. use of systemic steroids or heparin within 1 month prior to screening

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Retinal Research Institute Phoenix Arizona United States 85014
    2 Retina Institute of California Arcadia California United States 91007
    3 Retina-Vitreous Associates Medical Group Beverly Hills California United States 90211
    4 Retina Institute of California Palm Desert California United States 92260
    5 Colorado Retina Associates Golden Colorado United States 80401
    6 Retina Group of New England New London Connecticut United States 09320
    7 Retina Macula Specialists of Miami Miami Florida United States 33126
    8 Georgia Retina, P.C Marietta Georgia United States 30060
    9 Ophthalmic Consultants of Boston Boston Massachusetts United States 02114
    10 Retina Consultants of Nevada Las Vegas Nevada United States 89149
    11 Retina Associates of Western New York, PC Rochester New York United States 14620
    12 Charlotte Eye Ear Nose & Throat Assoc, PA Charlotte North Carolina United States 28210
    13 The Cleveland Clinic Cleveland Ohio United States 44915
    14 Retina Research Institute of Texas Abilene Texas United States 79606
    15 Retina Research Center Austin Texas United States 78705
    16 Retina Consultants of Houston Houston Texas United States 77030
    17 Medical Center Ophthalmology Associates San Antonio Texas United States 78240
    18 Retinal Consultants of San Antonio San Antonio Texas United States 78240
    19 Retina Consultants of Houston,The Woodlands The Woodlands Texas United States 77384
    20 University of Virginia Charlottesville Virginia United States 22903

    Sponsors and Collaborators

    • Taiwan Liposome Company

    Investigators

    • Study Director: Yvonne Shih, Taiwan Liposome Company, Ltd.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Taiwan Liposome Company
    ClinicalTrials.gov Identifier:
    NCT03093701
    Other Study ID Numbers:
    • TLC399A2002
    First Posted:
    Mar 28, 2017
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Group 1 Group 2 Group 3 Group 4
    Arm/Group Description TLC399 (ProDex) 0.36mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 50 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.84 mg DSP with 50 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid
    Period Title: Overall Study
    STARTED 10 10 11 0
    COMPLETED 10 7 11 0
    NOT COMPLETED 0 3 0 0

    Baseline Characteristics

    Arm/Group Title Group 1 Group 2 Group 3 Total
    Arm/Group Description TLC399 (ProDex) 0.36mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 50 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid Total of all reporting groups
    Overall Participants 10 10 11 31
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    72.1
    (10.40)
    63.5
    (12.55)
    68.5
    (8.20)
    68.1
    (10.70)
    Sex: Female, Male (Count of Participants)
    Female
    3
    30%
    4
    40%
    1
    9.1%
    8
    25.8%
    Male
    7
    70%
    6
    60%
    10
    90.9%
    23
    74.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    20%
    3
    30%
    2
    18.2%
    7
    22.6%
    Not Hispanic or Latino
    8
    80%
    7
    70%
    8
    72.7%
    23
    74.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    9.1%
    1
    3.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    1
    9.1%
    1
    3.2%
    Black or African American
    1
    10%
    1
    10%
    1
    9.1%
    3
    9.7%
    White
    9
    90%
    9
    90%
    9
    81.8%
    27
    87.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    10
    100%
    10
    100%
    11
    100%
    31
    100%
    RVO Type (Count of Participants)
    BRVO
    7
    70%
    6
    60%
    7
    63.6%
    20
    64.5%
    CRVO
    3
    30%
    4
    40%
    4
    36.4%
    11
    35.5%
    CST (study eye) (µm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [µm]
    530.6
    (133.56)
    776.9
    (288.67)
    702.1
    (195.15)
    670.9
    (231.75)
    BCVA (study eye) (letters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [letters]
    61.5
    (7.40)
    48.2
    (16.94)
    51.1
    (16.66)
    53.5
    (15.10)
    IOP (study eye) (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    12.4
    (2.63)
    13.5
    (3.41)
    13.6
    (2.69)
    13.2
    (2.88)

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Subjects With BCVA Gain of 15 or More Letters From Baseline in the Study Eye
    Description Proportion of subjects with BCVA gain of 15 or more letters from baseline in the study eye. Patients who received rescue medication/procedures within 6 months after the study treatment was initiated were considered failure to achieve a gain of at least 15 BCVA letters.
    Time Frame 6 months after dosing

    Outcome Measure Data

    Analysis Population Description
    The analysis population was based on subject's randomized treatment group.
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description TLC399 (ProDex) 0.36mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 50 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid
    Measure Participants 10 10 11
    Count of Participants [Participants]
    1
    10%
    1
    10%
    1
    9.1%

    Adverse Events

    Time Frame 14 days (screening) + 1 year
    Adverse Event Reporting Description Other (Not including serious) Adverse Events include both ocular (study eye only) and non-ocular adverse events. The safety population for AE reporting/analysis was based on the actual treatments received by the subjects.
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description TLC399 (ProDex) 0.36mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 100 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid TLC399 (ProDex) 0.6 mg DSP with 50 mM PL TLC399 (ProDex): 2-vial system: TLC399-DSP and TLC399-Lipid
    All Cause Mortality
    Group 1 Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 0/8 (0%) 0/13 (0%)
    Serious Adverse Events
    Group 1 Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 2/8 (25%) 1/13 (7.7%)
    Cardiac disorders
    Pericardial effusion 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Eye disorders
    Vitreous haze 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Vitreous haze leading to significant vision loss 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Gastrointestinal disorders
    Acute coliti 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Infections and infestations
    Pneumonia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Nervous system disorders
    Transient ischaemic attack 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Other (Not Including Serious) Adverse Events
    Group 1 Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/10 (100%) 8/8 (100%) 13/13 (100%)
    Blood and lymphatic system disorders
    Coagulopathy 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Anaemia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Cardiac disorders
    Cardiomyopathy 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Pericardial effusion 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Ear and labyrinth disorders
    Tinnitus 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Eye disorders
    Vitreous haze 10/10 (100%) 8/8 (100%) 13/13 (100%)
    Macular oedema 4/10 (40%) 2/8 (25%) 5/13 (38.5%)
    Visual acuity reduced 4/10 (40%) 4/8 (50%) 1/13 (7.7%)
    Conjunctival haemorrhage 4/10 (40%) 2/8 (25%) 1/13 (7.7%)
    Vitreous floaters 2/10 (20%) 2/8 (25%) 2/13 (15.4%)
    Vision blurred 3/10 (30%) 1/8 (12.5%) 1/13 (7.7%)
    Corneal oedema 1/10 (10%) 1/8 (12.5%) 1/13 (7.7%)
    Retinal vein occlusion 0/10 (0%) 0/8 (0%) 2/13 (15.4%)
    Optic disc hyperaemia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Retinal aneurysm 1/10 (10%) 0/8 (0%) 1/13 (7.7%)
    Retinal vascular disorder 0/10 (0%) 1/8 (12.5%) 1/13 (7.7%)
    Visual imparment 1/10 (10%) 0/8 (0%) 1/13 (7.7%)
    Vitrous detachment 0/10 (0%) 2/8 (25%) 0/13 (0%)
    Anterior chamber flare 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Cataract 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Cataract nulcear 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Conjunctival cyst 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Dry eye 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Eye pain 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Iris neovascularisation 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Macular fibrosis 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Macular pigmentation 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Maculopathy 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Retinal disorder 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Retinal exudates 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Retinal haemorrhage 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Retinal neovascularisation 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Retinal scar 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Vitreous disorder 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Vitreous haemorrhage 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Vitreous opacities 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Retinal thickening 1/10 (10%) 1/8 (12.5%) 0/13 (0%)
    Gastrointestinal disorders
    Nausea 0/10 (0%) 0/8 (0%) 2/13 (15.4%)
    Vomiting 0/10 (0%) 0/8 (0%) 2/13 (15.4%)
    Colitis 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Hiatus hernia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    General disorders
    Oedema peripheral 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Infections and infestations
    Nasopharyngitis 2/10 (20%) 0/8 (0%) 1/13 (7.7%)
    Upper respiratory tract infection 1/10 (10%) 0/8 (0%) 1/13 (7.7%)
    Urinary tract infection 1/10 (10%) 0/8 (0%) 1/13 (7.7%)
    Bronchitis 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Pneumonia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Sepsis 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Injury, poisoning and procedural complications
    Contusion 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Fall 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Foot fracture 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Investigations
    Intraocular pressure increased 2/10 (20%) 3/8 (37.5%) 4/13 (30.8%)
    Medication residue present 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Blood creatinine increased 0/10 (0%) 0/8 (0%) 2/13 (15.4%)
    Alanine aminotransferase increased 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Aspartate aminotransferase increased 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Blood potassium increased 0/10 (0%) 0/8 (0%) 2/13 (15.4%)
    Gamma-glutamyltransferase increased 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Blood alkaline phosphatase increased 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Blood cholesterol increased 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Blood urea increased 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Cardiac murmur 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Haemoglobin decreased 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Heart rate irregular 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/10 (10%) 0/8 (0%) 0/13 (0%)
    Diabetes mellitus inadequate control 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Hypokalaemia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/10 (0%) 1/8 (12.5%) 1/13 (7.7%)
    Back pain 0/10 (0%) 0/8 (0%) 2/13 (15.4%)
    Nervous system disorders
    Carotid artery stenosis 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Dementia 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Transient ischaemic attack 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Renal and urinary disorders
    Glycosuria 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Nephropathy 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Renal artery occlusion 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Urine abnormality 0/10 (0%) 1/8 (12.5%) 0/13 (0%)
    Respiratory, thoracic and mediastinal disorders
    Sinus pain 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Vascular disorders
    Hypertension 1/10 (10%) 1/8 (12.5%) 3/13 (23.1%)
    Hypotension 0/10 (0%) 0/8 (0%) 1/13 (7.7%)
    Peripheral arterial occlusive disease 0/10 (0%) 0/8 (0%) 1/13 (7.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Carl Brown
    Organization Taiwan Liposome Company
    Phone 886-2-2655-7377
    Email tlc_clinicaltrials@tlcbio.com
    Responsible Party:
    Taiwan Liposome Company
    ClinicalTrials.gov Identifier:
    NCT03093701
    Other Study ID Numbers:
    • TLC399A2002
    First Posted:
    Mar 28, 2017
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Nov 1, 2021