A Study of Multiple Intravitreal Injection TK001 in Patients With Neovascular Age-related Macular Degeneration

Neovascular Age-Related Macular Degeneration Clinical Trial

Official title:

A Multi-center, Open-label Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Multiple Intravitreal Injection TK001 in Patients With Neovascular Age-Related Macular Degeneration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03021785
• Other study ID #: Tmab-TK001-AMD-02
• Status: Recruiting
• Phase: Phase 1
• First received: January 12, 2017
• Last updated: February 27, 2018
• Start date: October 18, 2017
• Est. completion date: November 2018

Study information

• Verified date: February 2018
• Source: Jiangsu T-Mab Biopharma Co.,Ltd
• Contact: Hongwei Miao
• Phone: +86(21)61160520
• Email: miaohongwei[@]sh-qingfeng.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open-label study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of multiple intravitreal injection TK001 in patients with AMD. It consists of core study (12 weeks) and extension study (40 weeks).

Description:

This is a multicenter, open-label study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of multiple intravitreal injection TK001 in patients with AMD. It consists of core study (12 weeks) and extension study (40 weeks). In the core study, patients will receive their assigned dose in a 50-μL solution administered as an intravitreal injection every 4 weeks. In the extension study, they will be evaluated every 4 weeks and administrated PRN (pro re nata) with their assigned dose. The safety, pharmacokinetics, immunogenicity, and preliminary efficacy of TK001 will be evaluated in the core study, and will also be assessed in the extension study except pharmacokinetics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: November 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

Inclusion Criteria:

• Signed written informed consent

• Aged 45 - 80 years, male or female

• Diagnosed with neovascular AMD and with active lesions

• Best corrected VA for the studied eye=20/40

• With stable blood pressure, SBP<140 mmHg and DBP<90 mmHg

Exclusion Criteria:

Limitation of eye diseases

• With vitreous hemorrhage in studied eyes within two months preceding screening

• With geographic atrophy, epiretinal membrane or intensive subfoveal hard exudates which involved the foveal in studied eyes

• With opacity of refractive media(e.g. apparent cataract) or contraction of pupils which significantly interfered the visual test or assessment of anterior segment and fundus in studied eyes

• With pseudoexfoliation syndrome, intraocular hemorrhage resulting in decreased vision, rhegmatogenous retinal detachment, macular hole or choroidal neovascularization (CNV) for any reason except for AMD (such as fundus angioid streaks, ocular histoplasmosis, pathologic myopia, trauma) in studied eyes

• With apparent afferent pupillary defect(APD) in studied eyes

• With Polypoidal Choroidal Vasculopathy (PCV) or Retinal Angiomatous Proliferation (PAP) in studied eyes

• With intraocular pressure higher than 25mmHg despite treatment

• With VA for the fellow eyes<20/200

• With active inflammation in any eye, such as conjunctivitis, keratitis, scleritis, blepharitis, endophthalmitis and uveitis The treatment of the eye

• The studied eye received topical or grid photocoagulation more than twice or within 3 months preceding screening

• The studied eye received the following intraocular surgery or laser treatment in macular (such as macular translocation surgery, glaucoma filtering surgery, transpupillary thermotherapy, macular photocoagulation, vitreous cutting surgery, optic nerve dissection, optic nerve sheath membrane dissection). But patients who received verteporfin photodynamic therapy, cataract surgery or YAG posterior capsular dissection more than 3 months before screening will not be excluded.

• Any eye received antiangiogenic drugs within 2 months preceding screening or patients received systemic antiangiogenic drugs within 3 months preceding screening (such as pegaptanib, aflibercept, ranibizumab, bevacizumab or conbercept)

• Any eye received intraocular injection of corticosteroid drugs (such as triamcinolone acetonide) within 3 months preceding screening, or periocular injection of corticosteroid drugs within 1 month before screening Systemic diseases, treatment and other conditions

• With a history of allergy to sodium fluorescein and indocyanine green

• PLT=100×109/L, BUN or Cr>1.5×ULN(Upper Limit of Normal), TT(thrombin time) or PT(prothrombin time) >1.0×ULN(Upper Limit of Normal), take anti-platelet aggregation drugs or anticoagulants within 1 month before screening

• With surgery within 1 month before screening, or with unhealed 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 screening

• With activity disseminated intravascular coagulation and a tendency of significant bleeding before screening

• Systemic autoimmune disease

• Any uncontrolled diseases (such as severe systemic diseases of mental, neurological, cardiovascular, respiratory and malignancies)

• Pregnant and lactating women or patients who cannot take contraceptive measures

• Poor compliance

• Patients who participated other clinical trials within 30 days before screening or was taking other clinical trials at present

• Patients who is considered unsuitable for enrollment by investigator

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Biological:
• TK001
TK001 will be administered intravitreal injection.

Locations

Country	Name	City	State
China	Chinese Academy of Medicine Sciences,Peking Union Medical College Hospital	Beijing	Beijing
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	ShangHai General Hospital	Shanghai	Shanghai
China	The Eye Hospital of WMU(Zhejiang eye hospital)	Wenzhou	Zhejiang
China	Henan Province People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu T-Mab Biopharma Co.,Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001 in the first 12 weeks	Core Study	12 weeks
Primary	Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001 in the following 40 weeks	Extension Study	40 weeks
Secondary	Area under the plasma concentration-time curve (AUC)	Core Study	12 weeks
Secondary	Maximum plasma concentration (Cmax)	Core Study	12 weeks
Secondary	Time to reach maximum concentration (Tmax)	Core Study	12 weeks
Secondary	Elimination half-Life (T½)	Core Study	12 weeks
Secondary	Change from baseline in the Best Corrected Visual Acuity at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the mean central retinal thickness at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the thickness of choroidal neovascularization at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the retinal thickness in the site of lesion which was the thickest at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in macular volume at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the area of choroidal neovascularization at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the area of leakage at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the total lesion size at 12 weeks	Core Study	12 weeks
Secondary	Percentage of Participants Positive for anti-TK001 antibody at 12 weeks	Core Study	12 weeks
Secondary	Change from baseline in the Best Corrected Visual Acuity at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in the mean central retinal thickness at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in the thickness of choroidal neovascularization at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in the retinal thickness in the site of lesion which was the thickest at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in macular volume at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in the area of choroidal neovascularization at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in the area of leakage at 52 weeks	Extension Study	40 weeks
Secondary	Change from baseline in the total lesion size at 52 weeks	Extension Study	40 weeks
Secondary	Percentage of Participants Positive for anti-TK001 antibody at 52 weeks	Extension Study	40 weeks