Clinical Study of the Safety and Efficacy of BAT5906 Injection

Bio-Thera Solutions

Status and phase: Completed; Phase 2; Phase 1

Conditions: Diabetic Macular Edema

Treatments: Drug: 2.5mg of BAT5906; Drug: 4.0mg of BAT5906

Study type: Interventional

Funder types: Industry

Identifiers

NCT04772105

BAT5906-003-CR

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

2.5mg of BAT5906

Experimental group

Description:

Specification: 10mg/0.2ml/piece; route of administration: intravitreal injection; dose: 2.5mg/eye/time, 50μl; medication duration: once every 4 weeks, 6 consecutive times, then every 4 weeks Followed up once (the investigator judged to administer the drug as needed) and observed until the 48th week.

Treatment:

Drug: 2.5mg of BAT5906

4mg of BAT5906

Experimental group

Description:

Specification: 16mg/0.2ml/piece; route of administration: intravitreal injection; dose: 4mg/eye/time, 50μl; medication duration: once every 4 weeks, 3 consecutive times, then every 4 weeks Followed up once (the investigator judged to administer the drug as needed) and observed until the 48th week.

Treatment:

Drug: 4.0mg of BAT5906