Study of Two Multiple Intravitreal Doses of BAT5906 for Safety and Efficacy in Patients With Diabetic Macular Edema

NCT04772105 | Completed Phase 1

• 1 other identifier: BAT5906-003-CR
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 19

Brief Summary

This study is a multi-center, open, multiple-dose phase Ib/IIa clinical study evaluating the efficacy and safety of BAT5906 injection in patients with diabetic macular edema. BAT5906's phase I study on w-AMD shows that it is safe from 0.3-4.0 mg, and the higher dose (2.5 mg and 4 mg) may maintain the anti-VEGF effect for a longer time just like the same target drugs (such as brolucizumab and Abecip ) It has also been found in clinical studies that high doses can extend the dosing interval and reduce the dosing frequency. Therefore, in this study, two safe and effective doses were selected, and the optimal clinical effective dose and frequency of BAT5906 in DME were initially explored.

Conditions

Diabetic Macular Edema

Keywords

DME

Outcome Measures

Primary Outcomes (13)

• 1.1 Safety evaluation - Vital signs# the patient's body temperature；

  the patient's body temperature (axillary temperature) Any clinically significant abnormality should be reported as an adverse event and recorded in the original

  Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336

• 1.2 Safety evaluation - Vital signs# heart rate/pulse

  heart rate/pulse Any clinically significant abnormality should be reported as an adverse event and recorded in the original

  Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336

• 1.3 Safety evaluation - Vital signs# respiratory rate

  respiratory rate Any clinically significant abnormality should be reported as an adverse event and recorded in the original

  Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336

• 1.4 Safety evaluation - Vital signs# blood pressure

  blood pressure Any clinically significant abnormality should be reported as an adverse event and recorded in the original

  Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336

• Number of subjects with clinically significant abnormal physical examination signs identified byprotocol-specified full physical examination (general appearance, skin, lungs, heart, abdomen,extremities, musculoskeletal system)

  Full physical examination including general appearance, skin, pulmonary, cardiac, abdominalextremity and musculoskeletal assessments will be performed per study evaluation schedule. Allclinically significant abnormalities relative to baseline screening physical exam findings will bedocumented as adverse events. The primary summary metric is the proportion and number ofsubjects presenting 21 clinically significant abnormal physical examination finding during on-treatment study visits.

  Day-14~Day-1；Day84；Day168；Day336

• Number of participants with clinically significant abnormal laboratory findings

  Laboratory examinations include complete blood count, urinalysis, blood biochemistry (including liver and renal function), and coagulation function. Clinically significant changes from baseline will be assessed and reported as adverse events (AEs) based on CTCAE v4.0 criteria.

  Day-14~Day-1；Day84；Day168；Day336

• Number of participants with clinically significant abnormal ECG findings

  The 12-lead ECG will be performed to measure parameters including heart rate, PR interval, QRS duration, and QT/QTc interval. Clinically significant changes from baseline will be assessed by the investigator and recorded as adverse events

  Day-14~Day-1；Day84；Day168；Day336

• Anti-drug antibody (ADA);

  Plasma samples for anti-drug antibody (ADA) detection were collected to detect the positive incidence of ADA associated with plasma levels of BAT5906

  Screening (within 24 hours prior to first dose), Day 7 (168h), Day 14 (336h), prior to the 3rd dose (within 24 hours), and prior to the 5th dose through end of study visit (as needed)

• ocular and non-ocular adverse events (AE) and serious adverse events (SAE)

  Any adverse medical event that occurs after a subject participates in a clinical trial and receives the investigational drug, but is not necessarily cause-and-effect with the treatment. An adverse event can be any adverse or unexpected sign (including abnormal laboratory tests), symptom, or disease, whether or not it is drug related.

  Adverse events were collected from the time the patient signed the informed consent to the time 28 days after the last dication

• Efficacy evaluation

  2.1 Primary efficacy endpoint (study eye):Change from baseline in BCVA

  at Week 36

• Pharmacokinetic (PK) Evaluation

  Blood samples were collected from each treatment group throughout the study to determine the serum concentration of BAT5906 Injection. The PK blood sample collection schedule is detailed in the PK/VEGF/ADA Blood Collection Schedule.

  Once within 24 hours before administration.6 hours after administration, 24 hours after administration(once every 3 days) up to 672 hours after administration

• Peripheral Blood VEGF Assessment (VEGF)

  lood samples were collected from each treatment group throughout the study to measure blood VEGF concentrations. The blood sample collection schedule is detailed in the PK/VEGF/ADA Blood Sampling Schedule

  Once within 24 hours before administration.24 hours after administration (once every 7 days) up to 672hours after administration

• Immunogenicity Assessment

  Anti-BAT5906 antibodies (ADA) were detected. The blood sample collection schedule is detailed in the PK/VEGF/ADA Blood Sampling Schedule. Anti-drug antibodies (ADA) in serum were detected; samples confirmed positive for ADA were subsequently analyzed for neutralizing antibodies (Nab)

  First administration: within 24 hours prior to administration.168 hours and 336 hours after administration,and the second until the last administration: within 24 hours before administration

Secondary Outcomes (1)

• 1、Efficacy evaluation

  at Weeks 12, 24, and 48

Study Arms (2)

2.5mg of BAT5906

EXPERIMENTAL

Specification: 10 mg/0.2 mL per vial Route of Administration: Intravitreal Injection Dose: 2.5 mg per eye per administration (50 μL) Treatment Regimen: One injection every 4 weeks for 6 consecutive administrations; follow-up visits will be conducted every 4 weeks thereafter, with PRN retreatment permitted at the investigator's discretion, and subjects will be followed up until Week 48.

Drug: 2.5mg of BAT5906

4mg of BAT5906

EXPERIMENTAL

Specification: 16 mg/0.2 mL per vial； Route of Administration: Intravitreal Injection； Dose: 4 mg per eye per administration (50 μL)； Treatment Regimen: One injection every 4 weeks for 3 consecutive administrations; follow-up visits will be conducted every 4 weeks thereafter, with PRN retreatment permitted at the investigator's discretion, and subjects will be followed up until Week 48.

Drug: 4.0mg of BAT5906

Interventions

2.5mg of BAT5906 DRUG

Specification: 2.5mg of BAT5906

2.5mg of BAT5906

4.0mg of BAT5906 DRUG

Specification: 4.0mg of BAT5906

4mg of BAT5906

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Only the following criteria are met:
• Sign the informed consent voluntarily, willing and capable to follow the procedures of outpatient visits and research at the time specified in the trial
• Diagnosed with type 1 or type 2 diabetes, aged 18 to 80 years old;
• The drug treatment to control diabetes must be stable within 3 months before randomization and is expected to remain stable during the study period;
• Macular edema secondary to diabetes, and found to be involved in the macular center (fovea) of the research eye by OCT examination, confirmed by the reading center during screening;
• The study eye is assessed by OCT with CRT ≥ 250 µm;
• BCVA in the study eye is 73 to 21 letters (using the ETDRS chart, inclusive of boundary values, equivalent to a Snellen visual acuity score of 20/40 to 20/400 in the study eye).
• At the time of screening and baseline, the investigator judged that the contralateral eye was expected to not require any anti-VEGF treatment within 3 months (PK group only).

You may not qualify if:

• If a patient meets any of the following conditions, they cannot enter the study:
• There is structural damage to the center of the macula in the eye, and the best corrected vision may not be improved after the macular edema resolves, including atrophy of retinal pigment epithelial cells, subretinal fibrosis or scarring, and obvious macular ischemia (FFA suggests arching Obvious damage), macular anterior membrane involving fovea or organic hard exudate (as confirmed by the reading center before randomization);
• The research eye has iris lesions and neovascular glaucoma;
• Those who have no eye lens (except intraocular lens);
• The study eye has active hyperplastic diabetic retinopathy (PDR);
• The research eye has anyone other than diabetic macular edema that may confuse macular assessment or vision testing (retinal vascular occlusion, retinal detachment, vitreous macular traction, macular hole, preretinal fibrosis involving the macula, choroidal neovascularization, age Related macular degeneration, etc.);
• The research eye is accompanied by poorly controlled glaucoma, which is defined as the intraocular pressure still ≥21mmHg after treatment with anti-glaucoma drugs, or according to the judgment of the investigator;
• The research eye has undergone or may have undergone anti-glaucoma surgery during the study period (including trabeculectomy, sclerectomy and non-penetrating trabecular surgery, etc.);
• The research eye has undergone vitreoretinal surgery or scleral buckling;
• At the time of screening and baseline, the study eye had received laser photocoagulation (total retina or macular laser photocoagulation) within 90 days (including 90 days) or during the study period;
• At the time of screening and baseline, the study eye had any intraocular or perocular surgery within 90 days (including 90 days) (except for yttrium-aluminum-garnet (YAG) lens capsule incision and eyelid surgery for more than 30 days) ;
• A history of uveitis in any eye;
• Any eye has active ocular inflammation or infection (bacterial, viral, parasitic or fungal infection);
• At the time of screening and baseline, any eye had received intraocular anti-VEGF treatment within the first 90 days (including 90 days), such as ranibizumab, bevacizumab, abercept, compacept, etc.;
• At the time of screening and baseline, any eye has received intraocular, periocular, and subconjunctival corticosteroid treatment within the first 90 days (including 90 days);

Sponsors & Collaborators

• Bio-Thera Solutions: lead

Study Sites (19)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijiang, Beijing Municipality, 100730, China

Location

Eye Hospital of China Academy of Chinese Medical Sciences

Beijing, China

Location

Peking University First Hospital

Beijing, China

Location

The First Affiliated Hospital of Bengbu Medical College

Bengbu, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, China

Location

Henan Provincial Eye Hospital

Henan, China

Location

Jieyang People's Hospital

Jieyang, China

Location

The First Hospital of Jilin University

Jilin City, China

Location

The Affiliated Eye Hospital of Nanchang University

Nanchang, China

Location

Jiangsu Provincial Hospital of Traditional Chinese Medicine

Nanjing, China

Location

Affiliated Hospital of Nantong University

Nantong, China

Location

Affiliated Hospital of Qingdao University

Qingdao, China

Location

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong

Shantou, China

Location

West China Hospital of Sichuan University

Sichuan, China

Location

Wenzhou Medical University Affiliated Optometry Hospital

Wenzhou, China

Location

The Second Xiangya Hospital of Central South University

Xiangya, China

Location

Xiangya Hospital Central South University

Xiangya, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

Study Officials

• Youxin Chen

  Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: one investigational medicine with two different dose groups

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: February 26, 2021
• Study Start: October 16, 2020
• Primary Completion: November 6, 2023
• Study Completion: November 6, 2023
• Last Updated: July 14, 2026

Record last verified: 2024-04

Locations

CN (19)