A Dose Escalation Study of IBI302 in Patients With Wet Age-related Macular Degeneration

A Dose Escalation Phase I Clinical Study to Evaluate the Tolerability and Safety of IBI302 in Patients With Wet Age-related Macular Degeneration (AMD)

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.

Study Overview

• Status: Unknown
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: IBI302; Drug: IBI302; Drug: IBI302; Drug: IBI302; Drug: IBI302; Drug: IBI302

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort 1 IBI302 treated with first dose level of IBI302	Drug: IBI302; 0.05mg/eye;Intraocular injection; Drug: IBI302; 0.15mg/eye;Intraocular injection; Drug: IBI302; 0.5mg/eye;Intraocular injection; Drug: IBI302; 1mg/eye;Intraocular injection; Drug: IBI302; 2mg/eye;Intraocular injection; Drug: IBI302; 4mg/eye;Intraocular injection
Experimental: cohort 2 IBI302 treated with second dose level of IBI302	Drug: IBI302; 0.05mg/eye;Intraocular injection; Drug: IBI302; 0.15mg/eye;Intraocular injection; Drug: IBI302; 0.5mg/eye;Intraocular injection; Drug: IBI302; 1mg/eye;Intraocular injection; Drug: IBI302; 2mg/eye;Intraocular injection; Drug: IBI302; 4mg/eye;Intraocular injection
Experimental: cohort 3 IBI302 treated with third dose level of IBI302	Drug: IBI302; 0.05mg/eye;Intraocular injection; Drug: IBI302; 0.15mg/eye;Intraocular injection; Drug: IBI302; 0.5mg/eye;Intraocular injection; Drug: IBI302; 1mg/eye;Intraocular injection; Drug: IBI302; 2mg/eye;Intraocular injection; Drug: IBI302; 4mg/eye;Intraocular injection
Experimental: cohort 4 IBI302 treated with fourth dose level of IBI302	Drug: IBI302; 0.05mg/eye;Intraocular injection; Drug: IBI302; 0.15mg/eye;Intraocular injection; Drug: IBI302; 0.5mg/eye;Intraocular injection; Drug: IBI302; 1mg/eye;Intraocular injection; Drug: IBI302; 2mg/eye;Intraocular injection; Drug: IBI302; 4mg/eye;Intraocular injection
Experimental: cohort 5 IBI302 treated with fifth dose level of IBI302	Drug: IBI302; 0.05mg/eye;Intraocular injection; Drug: IBI302; 0.15mg/eye;Intraocular injection; Drug: IBI302; 0.5mg/eye;Intraocular injection; Drug: IBI302; 1mg/eye;Intraocular injection; Drug: IBI302; 2mg/eye;Intraocular injection; Drug: IBI302; 4mg/eye;Intraocular injection
Experimental: cohort 6 IBI302 treated with sixth dose level of IBI302	Drug: IBI302; 0.05mg/eye;Intraocular injection; Drug: IBI302; 0.15mg/eye;Intraocular injection; Drug: IBI302; 0.5mg/eye;Intraocular injection; Drug: IBI302; 1mg/eye;Intraocular injection; Drug: IBI302; 2mg/eye;Intraocular injection; Drug: IBI302; 4mg/eye;Intraocular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation indicators	Decreasing of BCVA; b) Changes in intraocular pressure compared with baseline; c) Incidence, relatedness and severity of all adverse events, treatment emergent adverse events and serious adverse events;	Baseline to Day43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy evaluation indicators	Changes in central subfield thickness by OCT compared with baseline; b) Changes in CNV area by FA compared with baseline; c) Changes in BCVA compared with baseline.	Baseline to Day43
Immunogenicity evaluation indicators	Positive rate of anti-drug antibody and neutralizing antibody	Baseline to Day43
The area under the drug-time curve from 0 to time t (AUC0-t)		Baseline to Day43
The area under the curve at the time of 0-infinity (AUC0-∞)		Baseline to Day43
The peak concentration (Cmax)		Baseline to Day43
The peak time (Tmax)		Baseline to Day43
Clearance rate (CL)		Baseline to Day43
Half-life (t1/2)		Baseline to Day43
Free and total VEGF concentration		Baseline to Day43

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Anticipated): February 21, 2020
• Study Completion (Anticipated): April 5, 2020

Study Registration Dates

• First Submitted: January 15, 2019
• First Submitted That Met QC Criteria: January 22, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulin Fc Fragments
• Other Study ID Numbers: CIBI302A101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No