The Study of Drug 601 in Patients With Wet Age-related Macular Degeneration (wAMD)

Phase I Clinical Trial of Recombinant Anti-VEGF Human Monoclonal Antibody in the Treatment of Wet Age-related Macular Degeneration

Multicenter study to evaluate the safety and tolerability in patients with wet Age-related macular degeneration (wAMD) treated with intravitreal recombinant humanized anti-VEGF monoclonal antibody

Study Overview

• Status: Unknown
• Conditions: Wet Age-related Macular Degeneration
• Intervention / Treatment: Drug: Drug 601; Drug: Drug 601; Drug: Drug 601; Drug: Drug 601; Drug: Drug 601; Drug: Drug 601

Detailed Description

According to the results of preclinical pharmacological research and clinical application of bevacizumab in ophthalmology Case, 601 will be developed as a drug candidate for the treatment of ocular diseases such as wAMD .Observe the safety and tolerability of the single and multiple doses of 601 in wAMD patients; study the pharmacokinetic characteristics of single and multiple doses of 601, Observe the Preliminary efficacy of 601 multiple injections with different doses in the treatment of patients with wAMD.

• Study Type: Interventional
• Enrollment (Anticipated): 67
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhang Ming, Ph.D; Phone Number: +86-028-85422452; Email: zhangmingscu@126.com
• Study Contact Backup: Name: Lu Fang; Phone Number: +86-028-85422452; Email: lufang@medicail.com.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Hospital

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:

1. Sign informed consent form and willing to be visited at the time specified in the trial;
2. Age ≥45 years and age ≤ 80 years;

3. The study eye must meet the following criteria:

   • Diagnosis of wAMD;
   • The presence of an primary or recurrent active choroidal neovascular (CNV) lesions in subfovea and para-fovea secondary to AMD;
   • Total area of all types of lesions ≤30mm2 (12 optic disc areas)
   • Best EDTRS letter score between 19 and 78(Snellen equivalent of 20/400 to 20/32);
   • No optometric media opacity and pupil shrinkage.
4. Best EDTRS letter score ≥19 (Snellen equivalent of 20/400 or better) in the fellow eyes.

Exclusion Criteria:

Any of the following eye conditions:

1. Any eye has active ocular infections (e.g.,blepharitis, keratitis, scleritis, conjunctivitis);
2. History of vitreous hemorrhage in the study eye within 2 months before screening;
3. scarring, fibrosis, or atrophy below with fovea in the study eye;
4. Received any drug treatment for CNV within 120 days prior to screening;
5. History of any following surgery in the study eye (e.g. PDT, macular transposition, Glaucoma filtration, subfoveal photocoagulation, vitrectomy and transpupular hyperthermia, and other surgery at the submacular or others for AMD) within 3 months before screening;
6. CNV in the study eye associated with other ocular diseases such as pathologic myopia, eye trauma, etc
7. History or present of uncontrolled glaucoma, history of glaucoma filtering surgery in the study eye;
8. Subretinal hemorrhage in the study eye, and the bleeding area ≥ 50% area of the total lesion;
9. History of rhegmatogenous retinal detachment or macular hole retinal detachment (stage 3 or 4) , retinal detachment, retinal pigment epithelium tear or macular area traction and macular area preretinal membrane and PCV in the study eye;

10. The study eye has no lens( except intraocular lens) or posterior capsular rupture of the lens;

    Any of the following general condition are present:

11. Medicines with toxicity to the lens are being used or may be used during the study period;
12. History of allergy to fluorescein sodium and allergies to protein products for treatment or diagnosis, history of allergy to more than two drugs and/or non-drug factors, or suffering from allergic diseases now.
13. History of surgery within 1 months before screening; and/or unhealed wounds, ulcers or fractures currently;
14. Suffering from systemic infections and requiring oral, intramuscular or intravenous medication;
15. History of stroke, myocardial infarction within 6 months before screening;
16. Active diffuse intravascular coagulation and obvious bleeding tendency within 3 months before screening;
17. Systemic immune diseases;
18. Uncontrolled blood pressure control ;
19. Diabetic patients with uncontrolled blood sugar;

20. Any uncontrolled clinical problems (such as severe mental, neurological, cardiovascular, respiratory and other systemic diseases and malignant tumours);

    Any of the following laboratory tests abnormalities(23-25):

21. Renal function impairment (Cr is 1.5 times higher than the upper limit of normal values in the local laboratory) Liver dysfunction (ALT or AST is 2 times higher than the upper limit of normal value in the local laboratory).

22. Abnormal coagulation function (prothrombin time >= the upper limit of normal value for 3 seconds) and activated partial thromboplastin time >= the upper limit of normal value for 10 seconds);

    Patients with childbearing age with any of the following conditions:

23. Those who do not use effective contraceptive measures;

    The following are not excluded:

24. Pregnancy and lactation women (pregnancy is defined as urinary pregnancy test positive in this study);

    Any other conditions:

25. Participation in any other drug clinical trials (except vitamins and minerals) in the past 1 month before screening ;
26. Researchers think it needs to be ruled out.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 601 dose level 1 treatment	Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.375mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.75mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.
Experimental: 601 dose level 2 treatment	Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.375mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.75mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.
Experimental: 601 dose level 3 treatment	Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.375mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.75mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.
Experimental: 601 dose level 4 treatment	Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.375mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.75mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.
Experimental: 601 dose level 5 treatment	Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.375mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.75mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.
Experimental: 601 dose level 6 treatment	Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.375mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(0.75mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(1.25mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.; Drug: Drug 601; Recombinant humanized anti-VEGF monoclonal antibody, drug 601(2.5mg), Vitreous injection, injection once every 4 weeks, three times continuously, then injection as needed within 9 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Maximum tolerated dose	From Day 0 up to Day 56/112.
DLT	Incidence of dose-limiting toxicities up to the Day 14 visit	From Day 0 up to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The maximum blood concentration after 601 drug enters the bloodstream	From Day 0 up to 56/112 days
t1/2	The half-life of drug 601, the time required for the terminal phase 601 drug concentration to drop by half	From Day 0 up to 56/112 days
AUC	Area under the concentration-time curve, reflect the characteristics of the exposure of 601 drug in the body.	From Day 0 up to 56/112 days
CL	Clearance rate of drug 601 from the central ventricle.	From Day 0 up to 56/112 days
MRT	The average length of time that the 601 drug stays in the body.	From Day 0 up to 56/112 days
λz	the ratio of the amount of elimination of 601 drug from the body per unit time to the total amount in the body	From Day 0 up to 56/112 days
Immunogenicity	Development of Anti-drug antibodies (ADA) after IVT injection of 601	From Day 0 up to 56/112 days
Pharmacokinetic (PK) profile	Study the change of 601 drug concentration in the blood with time by mathematical principles and methods	From Day 0 up to 56/112 days
Vd	The proportional constant between the amount of 601 drug in the body and the blood concentration when the 601 drug achieves the dynamic balance in the body.	From Day 0 up to 56/112 days
Biomarker	Detection of VEGF concentration.	From Day 0 up to 56/112 days
CRT	Changes in central retina thickness (CRT) at all time points compared to the baseline	From Day 0 up to 56/364 days
diseased region	Changes in the diseased region at all time points compared to the baseline	From Day 0 up to 56/364 days

Collaborators and Investigators

• Sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2018
• Primary Completion (Anticipated): March 15, 2021
• Study Completion (Anticipated): September 15, 2021

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 13, 2020
• Last Update Submitted That Met QC Criteria: July 8, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: 3SGJ601-AMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No