Evaluation the Pharmacokinetics, Safety, Tolerability of TK001 in Patients With Neovascular Age-related Macular Degeneration
Primary Purpose
Neovascular Age-related Macular Degeneration
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TK001
Sponsored by
About this trial
This is an interventional treatment trial for Neovascular Age-related Macular Degeneration focused on measuring Neovascular Age-Related Macular Degeneration, Subfoveal CNV, TK001
Eligibility Criteria
Inclusion Criteria:
- Patients or their legal representative signed informed consent
- Aged 45 years to 80 years, male or female
- Inpatient/Outpatient with confirmed neovascular AMD
- Best corrected VA for the studied eye≤20/100
- With primary or recurrent subfoveal choroidal neovascular (CNV) lesions secondary to neovascular AMD
- Blood pressure is stable with SBP<140 mmHg and DBP<90 mmHg with or without treatment
Exclusion Criteria:
Limitation of eye diseases
- The studied eye suffered intravitreal blood within two months prior to screening
- The studied eye suffered structural damage of retinal which involved macular center(such as epiretinal membrane, scars, laser burns, foveal atrophy, dense pigment changes, intensive subfoveal hard exudates)
- Apparent cataract, aphakia, pseudoexfoliation syndrome, intraocular hemorrhage resulting in decreased vision, rhegmatogenous retinal detachment, macular hole, diabetic retinopathy and diabetic macular disease which need to be treated, choroidal neovascularization (CNV) for any reason except for AMD (such as ocular histoplasmosis, pathologic myopia)
- Afferent pupillary defect(APD)
- Refractive media opacity and miosis which effect fundus examination
- Any eye of patient with active inflammation, such as conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis
- Choroidal neovascularization (CNV) for other reason, such as diabetic retinopathy, fundus angioid streaks, ocular histoplasmosis, pathologic myopia, trauma
The treatment of the eye
- The studied eye received topical or grid photocoagulation more than twice or within 3 months before screening
- The studied eye received any intraocular surgery or laser treatment (such as macular translocation surgery, glaucoma filtering surgery, verteporfin photodynamic therapy, transpupillary thermotherapy, foveal photocoagulation surgery, cataract surgery, vitreous cutting surgery, optic nerve incision operation, YAG posterior capsular incision surgery, sheath incision surgery or filtering surgery) within 3 months before screening
- Any eye received antiangiogenic drugs (including any anti-VEGF drugs) (such as pegaptanib [Macugen®], Aflibercept [Eylea®], ranibizumab [Lucentis ®], bevacizumab [Avastin ®]) within 3 months before baseline visit
- Any eye received intraocular injection of corticosteroid drugs (such as triamcinolone acetonide), or periocular injection of corticosteroid drugs within 1 months before screening
Systemic diseases,treatment and other conditions
- With a history of allergy to sodium fluorescein and indocyanine green
- PLT≤100×109/L, BUN, Cr, thrombin time and prothrombin time beyond the upper limit of the normal range; take anti-platelet aggregation drugs within a month prior to enrollment
- With surgery within one month prior to enrollment, or with unhealing wound, ulcer, fracture at present
- Diabetic patients without the control of glucose or accompanied by diabetic retinopathy
- With a history of myocardial infarction within 6 months before enrolled
- With activity disseminated intravascular coagulation and a tendency of significant bleeding prior to enrollment
- Systemic autoimmune disease
- Any uncontrolled clinical problems (such as severe systemic diseases of mental, neurological, cardiovascular, respiratory and malignancies)
- Pregnant and lactating women and patients who cannot take contraceptive measures
- Poor compliance
- The patients who is considered unsuitable for enrollment by investigator
Sites / Locations
- West China Hospital, Sichuan UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
TK001 0.1mg
TK001 0.5mg
TK001 1.0mg
TK001 2.0mg
TK001 2.5mg
TK001 3.0mg
Arm Description
Injection:single Intravitreal Injection
Injection:single Intravitreal Injection
Injection:single Intravitreal Injection
Biological: TK001 Injection:single Intravitreal Injection
Biological: TK001 Injection:single Intravitreal Injection
Injection:single Intravitreal Injection
Outcomes
Primary Outcome Measures
Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001
Secondary Outcome Measures
Best Corrected Visual Acuity (BCVA)
Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)
Maximum observed maximum plasma concentration (Cmax)
Time to reach the maximum observed plasma concentration (Tmax)
Frequency of subjects with anti-TK001 antibody
Anti- TK001 antibody will be detected pre-dose,14d and 42d.
Full Information
NCT ID
NCT02613559
First Posted
November 21, 2015
Last Updated
February 27, 2018
Sponsor
Jiangsu T-Mab Biopharma Co.,Ltd
1. Study Identification
Unique Protocol Identification Number
NCT02613559
Brief Title
Evaluation the Pharmacokinetics, Safety, Tolerability of TK001 in Patients With Neovascular Age-related Macular Degeneration
Official Title
A Single-center, Open-label, Single Ascending Dose Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Tolerability of Intravitreal TK001(Recombinant Humanized Anti-VEGF Monoclonal Antibody) in Subjects With Neovascular Age-Related Macular Degeneration
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 2015 (undefined)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
September 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu T-Mab Biopharma Co.,Ltd
4. Oversight
5. Study Description
Brief Summary
The purpose of this first-in-human study is to evaluate the safety, pharmacokinetics and tolerability of single ascending doses of TK001(Recombinant humanized anti-VEGF monoclonal antibody) to determine the maximum tolerated dose (MTD) in neovascular wet age-related macular degeneration (wAMD) subjects.
Detailed Description
This is an open-label, non-comparative, non-randomized, single-center phase 1 study evaluating pharmacokinetics, safety and tolerability of single intravitreal injections of TK001 in the patients with AMD.TK001 is a full-length recombinant humanized anti-VEGF monoclonal antibody. Compared with Avastin(a similar marketed product), the findings of preclinical studies suggested that TK001 might be more effective in inhibiting pathological angiogenesis, or to achieve equivalent effect with less dosage and better safety. In this study, participants will be administrated a single dose of TK001.Every subject will only accept one dose. In addition to safety and preliminary efficacy, pharmacokinetics and immunogenicity of TK001will be evaluated as well.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age-related Macular Degeneration
Keywords
Neovascular Age-Related Macular Degeneration, Subfoveal CNV, TK001
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TK001 0.1mg
Arm Type
Experimental
Arm Description
Injection:single Intravitreal Injection
Arm Title
TK001 0.5mg
Arm Type
Experimental
Arm Description
Injection:single Intravitreal Injection
Arm Title
TK001 1.0mg
Arm Type
Experimental
Arm Description
Injection:single Intravitreal Injection
Arm Title
TK001 2.0mg
Arm Type
Experimental
Arm Description
Biological: TK001 Injection:single Intravitreal Injection
Arm Title
TK001 2.5mg
Arm Type
Experimental
Arm Description
Biological: TK001 Injection:single Intravitreal Injection
Arm Title
TK001 3.0mg
Arm Type
Experimental
Arm Description
Injection:single Intravitreal Injection
Intervention Type
Biological
Intervention Name(s)
TK001
Intervention Description
Intravitreal Injection
Primary Outcome Measure Information:
Title
Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Best Corrected Visual Acuity (BCVA)
Time Frame
6 weeks
Title
Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Time Frame
Up to Day 42
Title
Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)
Time Frame
Up to Day 42
Title
Maximum observed maximum plasma concentration (Cmax)
Time Frame
Up to Day 42
Title
Time to reach the maximum observed plasma concentration (Tmax)
Time Frame
Up to Day 42
Title
Frequency of subjects with anti-TK001 antibody
Description
Anti- TK001 antibody will be detected pre-dose,14d and 42d.
Time Frame
Up to Day 42
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients or their legal representative signed informed consent
Aged 45 years to 80 years, male or female
Inpatient/Outpatient with confirmed neovascular AMD
Best corrected VA for the studied eye≤20/100
With primary or recurrent subfoveal choroidal neovascular (CNV) lesions secondary to neovascular AMD
Blood pressure is stable with SBP<140 mmHg and DBP<90 mmHg with or without treatment
Exclusion Criteria:
Limitation of eye diseases
The studied eye suffered intravitreal blood within two months prior to screening
The studied eye suffered structural damage of retinal which involved macular center(such as epiretinal membrane, scars, laser burns, foveal atrophy, dense pigment changes, intensive subfoveal hard exudates)
Apparent cataract, aphakia, pseudoexfoliation syndrome, intraocular hemorrhage resulting in decreased vision, rhegmatogenous retinal detachment, macular hole, diabetic retinopathy and diabetic macular disease which need to be treated, choroidal neovascularization (CNV) for any reason except for AMD (such as ocular histoplasmosis, pathologic myopia)
Afferent pupillary defect(APD)
Refractive media opacity and miosis which effect fundus examination
Any eye of patient with active inflammation, such as conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis
Choroidal neovascularization (CNV) for other reason, such as diabetic retinopathy, fundus angioid streaks, ocular histoplasmosis, pathologic myopia, trauma
The treatment of the eye
The studied eye received topical or grid photocoagulation more than twice or within 3 months before screening
The studied eye received any intraocular surgery or laser treatment (such as macular translocation surgery, glaucoma filtering surgery, verteporfin photodynamic therapy, transpupillary thermotherapy, foveal photocoagulation surgery, cataract surgery, vitreous cutting surgery, optic nerve incision operation, YAG posterior capsular incision surgery, sheath incision surgery or filtering surgery) within 3 months before screening
Any eye received antiangiogenic drugs (including any anti-VEGF drugs) (such as pegaptanib [Macugen®], Aflibercept [Eylea®], ranibizumab [Lucentis ®], bevacizumab [Avastin ®]) within 3 months before baseline visit
Any eye received intraocular injection of corticosteroid drugs (such as triamcinolone acetonide), or periocular injection of corticosteroid drugs within 1 months before screening
Systemic diseases,treatment and other conditions
With a history of allergy to sodium fluorescein and indocyanine green
PLT≤100×109/L, BUN, Cr, thrombin time and prothrombin time beyond the upper limit of the normal range; take anti-platelet aggregation drugs within a month prior to enrollment
With surgery within one month prior to enrollment, or with unhealing wound, ulcer, fracture at present
Diabetic patients without the control of glucose or accompanied by diabetic retinopathy
With a history of myocardial infarction within 6 months before enrolled
With activity disseminated intravascular coagulation and a tendency of significant bleeding prior to enrollment
Systemic autoimmune disease
Any uncontrolled clinical problems (such as severe systemic diseases of mental, neurological, cardiovascular, respiratory and malignancies)
Pregnant and lactating women and patients who cannot take contraceptive measures
Poor compliance
The patients who is considered unsuitable for enrollment by investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guangfu Li
Email
guangfuli@t-mab.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ming Zhang
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Zhang
12. IPD Sharing Statement
Learn more about this trial
Evaluation the Pharmacokinetics, Safety, Tolerability of TK001 in Patients With Neovascular Age-related Macular Degeneration
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