Clinical trial NCT03814291: A Dose Escalation Study of IBI302 in Patients With Wet Age-related Macular Degeneration
Official title: A Dose Escalation Phase I Clinical Study to Evaluate the Tolerability and Safety of IBI302 in Patients With Wet Age-related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neovascular Age-related Macular Degeneration
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-24
Enrollment: 31
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed for single-center, open-label, dose escalation phase I trial to evaluate the safety and tolerability of a single intravitreal injection of IBI302 in patients with wet AMD.


Eligibility criteria: Inclusion Criteria:

1. Male or female patient ≥ 50 yrs. of age.
2. Active subfoveal CNV secondary to wet AMD, with lesion size ≤ 12 optic discs in the study eye.
3. BCVA score of 10-73 letters using ETDRS charts (in 4 meters) in the study eye.
4. Central macular sub-field thickness according to OCT of at least 250 micron.
5. Clear stereoscopic fundus photography is obtained while the lens or other media is clear.
6. Female subjects of childbearing age or male subjects with childbearing age female partner agree to take effective contraceptive measures from the screening period to 3 months after the end of treatment.
7. Willing and able to sign informed consent form and comply with visit and study procedures per protocol.

Exclusion Criteria:

1. Presence of other causes of CNV other than wet AMD in the study eye.
2. Presence of active diabetic retinopathy in the study eye.
3. Presence of uncontrolled glaucoma in the study eye (defined as IOP≥30mmHg despite the standardized treatment).
4. Prior retinal detachment in the study eye.
5. Prior any treatment of following in the study eye:

   1. Anti-VEGF therapy within 6 months prior to screening;
   2. Anti-complement therapy;
   3. Laser photocoagulation;
   4. Photodynamic therapy;
   5. Transpupillary thermotherapy
   6. Intraocular surgery;
   7. Intraocular or periocular glucocorticoid injection therapy within 6 months prior to enrollment;
6. Presence of any non-AMD disease that may affect visual acuity in the study eye
7. Prior anti-VEGF therapy within 1 month before study drug administration or plan of above anti-VEGF therapy in the non-study eye during the whole study.
8. Oral steroid drugs within 1 month before study drug administration.
9. Presence of active intraocular or periocular inflammation or infection.
10. Diabetic patients have any of the following conditions:

    1. Microvascular and macrovascular complications;
    2. HbA1c\>7.5% when screening;
    3. Receiving more than two oral hypoglycemic agents;
    4. Receiving insulin or GLP-1 receptor agonist;
11. Hypertension (defined as systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg despite standard treatment);
12. Presence of any following laboratory abnormality:

    1. PLT\<100×109/L, INR≥1.5ULN, APTT≥ 10 seconds more than ULN;
    2. ALT or AST \>2ULN;
    3. Cr or Ur\>1.5ULN;
13. Large or medium surgery, or unhealed surgical incisions, ulcers or fractures within 1 month before study drug administration.

Primary outcomes:
measure: Safety evaluation indicators
timeFrame: Baseline to Day43
Secondary outcomes:
measure: Efficacy evaluation indicators
timeFrame: Baseline to Day43
measure: Immunogenicity evaluation indicators
timeFrame: Baseline to Day43
measure: The area under the drug-time curve from 0 to time t (AUC0-t)
timeFrame: Baseline to Day43
measure: The area under the curve at the time of 0-infinity (AUC0-∞)
timeFrame: Baseline to Day43
measure: The peak concentration (Cmax)
timeFrame: Baseline to Day43
measure: The peak time (Tmax)
timeFrame: Baseline to Day43
measure: Clearance rate (CL)
timeFrame: Baseline to Day43
measure: Half-life (t1/2)
timeFrame: Baseline to Day43
measure: Free and total VEGF concentration
timeFrame: Baseline to Day43
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
Study officials:
References:
citation: Yang S, Li T, Jia H, Gao M, Li Y, Wan X, Huang Z, Li M, Zhai Y, Li X, Yang X, Wang T, Liang J, Gu Q, Luo X, Qian L, Lu S, Liu J, Song Y, Wang F, Sun X, Yu D. Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy. Sci Transl Med. 2022 Jun;14(647):eabj2177. doi: 10.1126/scitranslmed.abj2177. Epub 2022 Jun 1.