Clinical trial NCT04772105: Clinical Study of the Safety and Efficacy of BAT5906 Injection
Official title: Phase Ib/IIa Clinical Study of the Safety and Efficacy of BAT5906 Injection in Patients With Diabetic Macular Edema With Multiple Changes of Intravitreal Two Doses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetic Macular Edema
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2021-02-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: one investigational medicine with two different dose groups
Primary purpose: TREATMENT

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 effect for longer; 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.


Eligibility criteria: Inclusion Criteria:

* Only the following criteria are met:

  1. Sign the informed consent voluntarily, willing and capable to follow the procedures of outpatient visits and research at the time specified in the trial
  2. Diagnosed with type 1 or type 2 diabetes, aged 18 to 80 years old;
  3. The drug treatment to control diabetes must be stable within 3 months before randomization and is expected to remain stable during the study period;
  4. 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;
  5. The CRT of the research eye evaluated by OCT examination is ≥300 μM, confirmed by the reading center during screening;
  6. The BCVA of the research eye is 73-24 letters (using the ETDRS table, including the boundary value, which is equivalent to the Snellen visual acuity score of the research eye equal to 20/40 -20/400);
  7. Contralateral eye BCVA ≥ 34 letters (using ETDRS table, equivalent to snellen vision ≥ 20/200). Note: If both eyes meet the inclusion criteria, the eye with poor baseline vision is selected as the research eye;
  8. 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).

Exclusion Criteria:

* If a patient meets any of the following conditions, they cannot enter the study:

Eye exclusion criteria:

1. 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);
2. The research eye has iris lesions and neovascular glaucoma;
3. Those who have no eye lens (except intraocular lens);
4. The study eye has active hyperplastic diabetic retinopathy (PDR);
5. 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.);
6. 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;
7. 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.);
8. The research eye has undergone vitreoretinal surgery or scleral buckling;
9. 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;
10. 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) ;
11. A history of uveitis in any eye;
12. Any eye has active ocular inflammation or infection (bacterial, viral, parasitic or fungal infection);
13. 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.;
14. 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:
15. 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);
16. Abnormal blood coagulation function (prothrombin time ≥ upper limit of normal value 3 seconds, activated partial thromboplastin time ≥ upper limit of normal value 10 seconds);
17. 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:
18. Myocardial infarction or stroke occurred within 6 months before the first dose;
19. Poorly controlled diabetes \[defined as glycated hemoglobin (HbA1c)\>9%)\];
20. Accompanied by uncontrollable hypertension (defined as blood pressure \>150/100 mmHg after treatment with antihypertensive drugs);
21. 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;
22. Those who have undergone surgery within 1 month and have not healed, or according to the investigator's judgment;
23. 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;
24. Allergy or contraindications to known research drugs or their ingredients, fluorescein or povidone iodine;
25. Those who participated in clinical trials of any drugs (except vitamins and minerals) or devices 90 days before the first dose (including 90 days);
26. 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);
27. The researchers believe that there are other conditions that need to be excluded.

Primary outcomes:
measure: Vital signs（ body temperature）
timeFrame: After patient resting for more than 3 minutes
measure: Vital signs（heart rate/pulse）
timeFrame: After patient resting for more than 3 minutes
measure: Vital signs（respiratory rate）
timeFrame: After patient resting for more than 3 minutes
measure: Vital signs（blood pressure）
timeFrame: After patient resting for more than 3 minutes
measure: physical examination
timeFrame: 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
measure: laboratory examination（blood routine）
timeFrame: Screening period，Week 12, Week 24, Week 48 of the last visit
measure: laboratory examination（outine urine）
timeFrame: Screening period，Week 12, Week 24, Week 48 of the last visit
measure: laboratory examination（blood biochemical examination）
timeFrame: Screening period，Week 12, Week 24, Week 48 of the last visit
measure: laboratory examination（blood coagulation function）
timeFrame: Screening period，Week 12, Week 24, Week 48 of the last visit
measure: electrocardiogram（12- Lead ECG）
timeFrame: 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
measure: anti-drug antibody (ADA)
timeFrame: 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
measure: ocular and non-ocular adverse events (AE) and serious adverse events (SAE)
timeFrame: Adverse events were collected from the time the patient signed the informed consent to the time 28 days after the last dication
Secondary outcomes:
measure: Effectiveness evaluation
timeFrame: Week 24
measure: Effectiveness evaluation
timeFrame: Week 12 and 48
measure: Effectiveness evaluation
timeFrame: at weeks 12, 24, and 48
measure: Effectiveness evaluation
timeFrame: at weeks 12, 24, and 48
measure: Effectiveness evaluation
timeFrame: 24 weeks and 48 weeks
Other outcomes:
measure: Pharmacokinetic (PK) evaluation
timeFrame: Once within 24 hours before administration.6 hours after administration, 24 hours after administration (once every 3 days) up to 672 hours after administration
measure: Peripheral blood VEGF evaluation (VEGF)
timeFrame: Once within 24 hours before administration.24 hours after administration (once every 7 days) up to 672 hours after administration
measure: Evaluation of immunogenicity
timeFrame: 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
Locations:
city: Beijiang
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Eye Hospital of China Academy of Chinese Medical Sciences
city: Beijing
country: China
facility: Peking University First Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Henan
country: China
facility: Henan Provincial Eye Hospital
city: Jieyang
country: China
facility: Jieyang People's Hospital
city: Jilin
country: China
facility: The First Hospital of Jilin University
city: Nanchang
country: China
facility: The Affiliated Eye Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Provincial Hospital of Traditional Chinese Medicine
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
city: Qingdao
country: China
facility: Affiliated Hospital of Qingdao University
city: Shantou
country: China
facility: Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong
city: Sichuan
country: China
facility: West China Hospital of Sichuan University
city: Wenzhou
country: China
facility: Wenzhou Medical University Affiliated Optometry Hospital
city: Xiangya
country: China
facility: The Second Xiangya Hospital of Central South University
city: Xiangya
country: China
facility: Xiangya Hospital Central South University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Peking Union Medical College
name: Youxin Chen
role: PRINCIPAL_INVESTIGATOR
References: