A Randomized, Double-blind, Two-group Parallel, Positive-controlled Clinical Phase I Trial Comparing the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of CMAB818 and Lucentis® in Patients With Wet Age-related Macular Degeneration.
Overview
- Phase
- Phase 1
- Intervention
- CMAB818
- Conditions
- Wet Age-related Macular Degeneration
- Sponsor
- Shanghai Biomabs Pharmaceutical Co., Ltd.
- Enrollment
- 24
- Locations
- 4
- Primary Endpoint
- Number of Participants With Adverse Events That Are Related to Treatment
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a randomized, double-blind, two-group parallel, positive-controlled clinical Phase I trial comparing the safety, pharmacokinetics, pharmacodynamics and efficacy of CMAB818 and Lucentis® in patients with wet age-related macular degeneration.
Detailed Description
This is a phase I, randomized, double-blind, two-group parallel, positive-controlled clinical trial at four sites. Subjects will be sequentially enrolled according to the protocol in one of two cohorts and receive a single 0.5mg of CMAB818 or Lucentis® through intravitreal injection. The primary objective is to assess the initial clinical safety of intravitreal injection of CMAB818 or Lucentis® in patients with wet age-related macular degeneration (wet-AMD). The secondary objective are to assess immnogenicity, pharmacokinetic, pharmacodynamics and the initial clinical efficacy of intravitreal injection of CMAB818 or Lucentis® in patients with wet age-related macular degeneration (wet-AMD).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Sign the informed consent, and able to receive follow-up according to the time stipulated by the trial;
- •50 years≤age≤80 years, male or female;
- •The target eye must meet the following requirements: newly occurring or relapsed subfoveal and perifoveal active choroidal neovascularization (CNV) lesions secondary to AMD; the best corrected visual acuity between 78-19 letters (including the boundary value, using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts, equivalent to Snellen visual acuity of 20/32 to 20/400); no refractive media opacity or myosis affecting fundus examination;
- •The best corrected visual acuity of the subject's non-target eye≥19 letters (using ETDRS charts, equivalent to Snellen visual acuity of 20/400).
Exclusion Criteria
- •Previously received anti-VEGF drug treatment in either eye within 3 months before screening (e.g., aflibercept\<Eylea®\>, ranibizumab\<Lucentis®\>, bevacizumab\<Avastin®\>, Conbercept\<Lumitin®\>, etc.);
- •Active eye infection in either eye within 1 months before screening (including but not limited to Blepharitis, Conjunctivitis infective, Keratitis, Scleritis, Endophthalmitis);
- •History of vitreous hemorrhage within 3 months before screening;
- •History or presence of uncontrolled glaucoma (defined as intraocular pressure(IOP)\>25 mmHg despite treatment with maximal medical therapy),or the optic fovea/optical disc ratio of the target eye caused by severe glaucoma \> 0.8;
- •Previously received subconjunctival/intravitreal corticosteroids injection within 3 months (including subconjunctival/intravitreal long-acting implants within 6 months), or local ocular corticosteroids treatment in the target eye within 1 month before screening;
- •Previously received the following ophthalmic surgery such as verteporfin photodynamic therapy (PDT), macular translocation, glaucoma filtering, subfoveal laser photocoagulation, vitrectomy and transpupillary thermotherapy, and other submacular surgery or surgery used to treat age-related macular degeneration in the target eye;
- •Other ocular diseases other than wAMD that affect the central vision, such as dry AMD, venous occlusion, uveitis, diabetic retinopathy, vascular-like streaks, pathological myopia, retinal detachment, macular hole, etc. in the target eye;
- •Aphakia (excluding intraocular lenses) or rupture of the posterior lens capsule in the target eye \[except for yttrium aluminum garnet (YAG) laser posterior capsulotomy after intraocular lens implantation\];
- •History of rhegmatogenous retinal detachment or macular hole retinal detachment (stage 3 or 4), with retinal detachment, retinal pigment epithelial tear, or retinal traction in the macular area and epiretinal disease in the macular area in the target eye;
- •Current use or may need to use systemic drugs that can cause crystal toxicity, such as psoralen, risedronate sodium, tamoxifen, etc.;
Arms & Interventions
CMAB818
0.5 mg by intravitreal injection once on the first day.
Intervention: CMAB818
Lucentis®
0.5 mg by intravitreal injection once on the first day.
Intervention: Lucentis®
Outcomes
Primary Outcomes
Number of Participants With Adverse Events That Are Related to Treatment
Time Frame: 0~42 days
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant graded according to the common terminology criteria for adverse events (CTCAE) v.5.0 criteria, including clinically-significant changes in physical examinations, laboratory safety tests, ECG and vital signs
Secondary Outcomes
- Cmax(0~42 days)
- Half-life (t1/2)(0~42 days)
- Mean change in leakage area from baseline(0~42 days)
- Percentage of neutralizing antibody(0~42 days)
- Pharmacodynamics(0~42 days)
- AUC(0-t)(0~42 days)
- CL(0~42 days)
- Number of Participants With anti-drug antibody(0~42 days)
- Mean change in lesion area from baseline(0~42 days)
- Mean change in best corrected visual acuity (BCVA) from baseline(0~42 days)
- Mean change in central retinal thickness from baseline(0~42 days)