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

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

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.

Study Overview

• Status: Unknown
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Biological: TK001

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 Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Guangfu Li; Email: guangfuli@t-mab.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Ming Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

  1. The studied eye suffered intravitreal blood within two months prior to screening
  2. 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)
  3. 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)
  4. Afferent pupillary defect(APD)
  5. Refractive media opacity and miosis which effect fundus examination
  6. Any eye of patient with active inflammation, such as conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis
  7. Choroidal neovascularization (CNV) for other reason, such as diabetic retinopathy, fundus angioid streaks, ocular histoplasmosis, pathologic myopia, trauma

• The treatment of the eye

  1. The studied eye received topical or grid photocoagulation more than twice or within 3 months before screening
  2. 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
  3. 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
  4. 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

  1. With a history of allergy to sodium fluorescein and indocyanine green
  2. 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
  3. With surgery within one month prior to enrollment, or with unhealing wound, ulcer, fracture at present
  4. Diabetic patients without the control of glucose or accompanied by diabetic retinopathy
  5. With a history of myocardial infarction within 6 months before enrolled
  6. With activity disseminated intravascular coagulation and a tendency of significant bleeding prior to enrollment
  7. Systemic autoimmune disease
  8. Any uncontrolled clinical problems (such as severe systemic diseases of mental, neurological, cardiovascular, respiratory and malignancies)
  9. Pregnant and lactating women and patients who cannot take contraceptive measures
  10. Poor compliance
  11. The patients who is considered unsuitable for enrollment by investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Anti- TK001 antibody will be detected pre-dose,14d and 42d.	Up to Day 42

Collaborators and Investigators

• Sponsor: Jiangsu T-Mab Biopharma Co.,Ltd

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: November 21, 2015
• First Submitted That Met QC Criteria: November 21, 2015
• First Posted (Estimate): November 24, 2015

Study Record Updates

• Last Update Posted (Actual): March 1, 2018
• Last Update Submitted That Met QC Criteria: February 27, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Neovascular Age-Related Macular Degeneration, Subfoveal CNV, TK001
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: Tmab-TK001-AMD-01