Phase Ib/IIa Study to Evaluate the Safety and Efficacy of Intravitreal Administration of Two Doses of BAT5906 Injection With Multiple Dosing Regimens in Patients With Diabetic Macular Edema
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 19
- 主要终点
- Vital signs（ body temperature）
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •BCVA in the fellow eye is ≥24 letters (using the ETDRS chart, equivalent to Snellen visual acuity ≥20/320). Note: If both eyes meet the inclusion criteria, the eye with the worse baseline visual acuity will be selected as 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).
排除标准
- •If a patient meets any of the following conditions, they cannot enter the study:
- •Eye exclusion criteria:
- •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);
- •Exclusion criteria for abnormal conditions in laboratory inspection:
- •Abnormal liver and kidney function (this test specifies that ALT and AST should not be higher than the upper limit of the normal value of the laboratory in the center by 2.5 times; Crea and BUN should not be higher than the upper limit of the normal value of the laboratory in the center by 2 times);
- •Abnormal blood coagulation function (prothrombin time ≥ upper limit of normal value 3 seconds, activated partial thromboplastin time ≥ upper limit of normal value 10 seconds);
- •Any one of the infected patients: active hepatitis B (if HBsAg(+) requires HBV DNA must be> 500 IU/mL or the hospital maximum limit), hepatitis C, AIDS or syphilis (positive RPR test);
- •Other exclusion criteria:
- •Myocardial infarction or stroke occurred within 6 months before the first dose;
- •Poorly controlled diabetes mellitus [defined as glycosylated hemoglobin (HbA1c) > 10%];
- •Accompanied by uncontrollable hypertension (defined as blood pressure >150/100 mmHg after treatment with antihypertensive drugs);
- •Patients who took large doses of oral or injectable corticosteroids and other hormonal drugs (>10 mg prednisolone or the same dose/day) within 6 months before screening, but patients who used steroid drugs for inhalation, nasal cavity or local skin small doses except;
- •Those who have undergone surgery within 1 month and have not healed, or according to the investigator's judgment;
- •There is a history of contraindications to the study drug, metabolic dysfunction, physical examination results, or a disease or symptom that is reasonably suspected of being based on clinical laboratory results is a contraindication to the study drug, which may affect the judgment of the study results, or make the subject suffer Higher risk of complications;
- •Allergy or contraindications to known research drugs or their ingredients, fluorescein or povidone iodine;
- •Those who participated in clinical trials of any drugs (except vitamins and minerals) or devices 90 days before the first dose (including 90 days);
- •Women who are pregnant, pregnant or breastfeeding (pregnancy is defined as a positive blood/urine pregnancy test in this trial); male or female subjects of fertility do not agree to the entire study period and within 3 months after the end of the visit period Take appropriate contraceptive measures (such as IUD, birth control pills or condoms, etc.). For women who have not been menopausal or have been menopausal but have not met the menopause time continuously for more than 12 months, and have not undergone sterilization surgery (ovarian and/or hysterectomy), they are defined as having fertility. The definition of fertility may be adjusted according to local standards in each region.
- •Note: High-efficiency contraception methods include total abstinence, IUD, double barrier method (eg condom + diaphragm with spermicides, implanted contraceptives, hormonal contraceptives [contraceptives, implanted contraceptives, transdermal Patches, hormone-vaginal devices or sustained-release injections], or the partner has undergone a vasectomy and is confirmed to have no sperm);
- •The researchers believe that there are other conditions that need to be excluded.
研究组 & 干预措施
2.5mg of BAT5906
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.
干预措施: 2.5mg of BAT5906 (Drug)
4mg of BAT5906
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.
干预措施: 4.0mg of BAT5906 (Drug)
结局指标
主要结局
Vital signs（ body temperature）
时间窗: After patient resting for more than 3 minutes
the patient's body temperature (axillary temperature) Any clinically significant abnormality should be reported as an adverse event and recorded in the original
physical examination
时间窗: The investigator or other authorized and qualified investigator shall perform the prescribed physical examination according to the evaluation schedule. During the visit, the investigator performed a physical examination as indicated by symptoms
Physical examination should include at least general conditions, head and face, skin, lymph nodes, ears, nose, throat, respiratory system, cardiovascular system, abdomen (including liver and spleen), genitourinary system, musculoskeletal system, nervous system, and mental condition
laboratory examination（blood coagulation function）
时间窗: Screening period，Week 12, Week 24, Week 48 of the last visit
In the test process will be carried out in accordance with the testing program flow chart of blood coagulation function, the laboratory testing results of the subjects to evaluate the change of relative to the baseline, the each evaluate clinical significance of abnormal experimental value, the researchers don't think with basic diseases related to abnormal subjects as AE record
electrocardiogram（12- Lead ECG）
时间窗: Screening period of the first visit: Week 12 of the fifth visit, Week 24 of the eighth visit, and Week 48 of the last visit
During the trial, the examination of the electrocardiogram (ecg) method must be consistent, and to evaluate the clinical significance of the results, will any researchers to make judgment for clinical significance of abnormal as adverse events were reported, and recorded in the original records and case report form, the subjects in the process of the entire study if there is clinical indications by researchers to determine whether the need for ecg examination.
anti-drug antibody (ADA)
时间窗: 24 hours before 1, 2, 3, 4 dosing, 5 dosing to last visit, each dosing before and 24 hours before the last visit as needed
Plasma samples for anti-drug antibody (ADA) detection were collected to detect the positive incidence of ADA associated with plasma levels of BAT5906
ocular and non-ocular adverse events (AE) and serious adverse events (SAE)
时间窗: Adverse events were collected from the time the patient signed the informed consent to the time 28 days after the last dication
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.
laboratory examination（blood routine）
时间窗: Screening period，Week 12, Week 24, Week 48 of the last visit
In the test process will be carried out in accordance with the testing program flow chart of blood routine, the laboratory testing results of the subjects to evaluate the change of relative to the baseline, the each evaluate clinical significance of abnormal experimental value, the researchers don't think with basic diseases related to abnormal subjects as AE record
Vital signs（heart rate/pulse）
时间窗: After patient resting for more than 3 minutes
heart rate/pulse Any clinically significant abnormality should be reported as an adverse event and recorded in the original
Vital signs（respiratory rate）
时间窗: After patient resting for more than 3 minutes
respiratory rate Any clinically significant abnormality should be reported as an adverse event and recorded in the original
Vital signs（blood pressure）
时间窗: After patient resting for more than 3 minutes
blood pressure Any clinically significant abnormality should be reported as an adverse event and recorded in the original
laboratory examination（outine urine）
时间窗: Screening period，Week 12, Week 24, Week 48 of the last visit
In the test process will be carried out in accordance with the testing program flow chart of routine urine , the laboratory testing results of the subjects to evaluate the change of relative to the baseline, the each evaluate clinical significance of abnormal experimental value, the researchers don't think with basic diseases related to abnormal subjects as AE record
laboratory examination（blood biochemical examination）
时间窗: Screening period，Week 12, Week 24, Week 48 of the last visit
In the test process will be carried out in accordance with the testing program flow chart of blood biochemical examination, the laboratory testing results of the subjects to evaluate the change of relative to the baseline, the each evaluate clinical significance of abnormal experimental value, the researchers don't think with basic diseases related to abnormal subjects as AE record
1.2 Safety evaluation - Vital signs# heart rate/pulse
时间窗: Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336
heart rate/pulse Any clinically significant abnormality should be reported as an adverse event and recorded in the original
1.1 Safety evaluation - Vital signs# the patient's body temperature；
时间窗: Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336
the patient's body temperature (axillary temperature) Any clinically significant abnormality should be reported as an adverse event and recorded in the original
1.3 Safety evaluation - Vital signs# respiratory rate
时间窗: Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336
respiratory rate Any clinically significant abnormality should be reported as an adverse event and recorded in the original
1.4 Safety evaluation - Vital signs# blood pressure
时间窗: Day-14~Day-1；Day0；Day28；Day56；Day84；Day112；Day140；Day168；Day196；Day224；Day252；Day280；Day308；Day336
blood pressure Any clinically significant abnormality should be reported as an adverse event and recorded in the original
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)
时间窗: Day-14~Day-1；Day84；Day168；Day336
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.
Number of participants with clinically significant abnormal laboratory findings
时间窗: Day-14~Day-1；Day84；Day168；Day336
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.
Number of participants with clinically significant abnormal ECG findings
时间窗: Day-14~Day-1；Day84；Day168；Day336
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
Anti-drug antibody (ADA);
时间窗: 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)
Plasma samples for anti-drug antibody (ADA) detection were collected to detect the positive incidence of ADA associated with plasma levels of BAT5906
Efficacy evaluation
时间窗: at Week 36
2.1 Primary efficacy endpoint (study eye):Change from baseline in BCVA
Pharmacokinetic (PK) Evaluation
时间窗: Once within 24 hours before administration.6 hours after administration, 24 hours after administration(once every 3 days) up to 672 hours after administration
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.
Peripheral Blood VEGF Assessment (VEGF)
时间窗: Once within 24 hours before administration.24 hours after administration (once every 7 days) up to 672hours after administration
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
Immunogenicity Assessment
时间窗: 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
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)
次要结局
- Effectiveness evaluation(24 weeks and 48 weeks)
- 1、Efficacy evaluation(at Weeks 12, 24, and 48)