Evaluation the Pharmacokinetics, Safety, Tolerability of TK001 in Patients With Neovascular Age-related Macular Degeneration

Sponsor

Jiangsu T-Mab Biopharma Co.,Ltd (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02613559

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration	Biological: TK001	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TK001 0.1mg Injection:single Intravitreal Injection	Biological: TK001 Intravitreal Injection
Experimental: TK001 0.5mg Injection:single Intravitreal Injection	Biological: TK001 Intravitreal Injection
Experimental: TK001 1.0mg Injection:single Intravitreal Injection	Biological: TK001 Intravitreal Injection
Experimental: TK001 2.0mg Biological: TK001 Injection:single Intravitreal Injection	Biological: TK001 Intravitreal Injection
Experimental: TK001 2.5mg Biological: TK001 Injection:single Intravitreal Injection	Biological: TK001 Intravitreal Injection
Experimental: TK001 3.0mg Injection:single Intravitreal Injection	Biological: TK001 Intravitreal Injection

Outcome Measures

Primary Outcome Measures

Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001 [6 weeks]

Secondary Outcome Measures

Best Corrected Visual Acuity (BCVA) [6 weeks]
Area under the plasma concentration-time curve from time zero to infinity (AUCinf) [Up to Day 42]
Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t) [Up to Day 42]
Maximum observed maximum plasma concentration (Cmax) [Up to Day 42]
Time to reach the maximum observed plasma concentration (Tmax) [Up to Day 42]
Frequency of subjects with anti-TK001 antibody [Up to Day 42]
Anti- TK001 antibody will be detected pre-dose,14d and 42d.

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610000

Sponsors and Collaborators

Jiangsu T-Mab Biopharma Co.,Ltd

Investigators

Principal Investigator: Ming Zhang, West China Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jiangsu T-Mab Biopharma Co.,Ltd

ClinicalTrials.gov Identifier:

NCT02613559

Other Study ID Numbers:

Tmab-TK001-AMD-01

First Posted:

Nov 24, 2015

Last Update Posted:

Mar 1, 2018

Last Verified:

Feb 1, 2018

Keywords provided by Jiangsu T-Mab Biopharma Co.,Ltd

Neovascular Age-Related Macular Degeneration, Subfoveal CNV, TK001

Additional relevant MeSH terms:

Macular Degeneration

Wet Macular Degeneration

Study Results

No Results Posted as of Mar 1, 2018