KHK4951 for Age-Related Macular Degeneration

Recruiting at 93 trial locations

Overseen By Kyowa Kirin, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kyowa Kirin Co., Ltd.

Must not be taking: Corticosteroids, Anti-VEGF, others

Disqualifiers: Glaucoma, Retinal detachment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing special eye drops called KHK4951 to help people with a vision problem known as nAMD. The drops aim to improve vision by addressing abnormal blood vessels in the eye.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have been treated with certain eye medications like ranibizumab, bevacizumab, or aflibercept within the last 12 weeks, you may not be eligible to participate.

What data supports the effectiveness of the drug KHK4951 for age-related macular degeneration?

Research shows that ziv-aflibercept, which is similar to aflibercept, has been effective in improving vision and reducing retinal fluid in patients with age-related macular degeneration. It has a similar safety profile to other treatments and has shown positive results in related eye conditions. ^{1 2 3 4 5}

Is KHK4951 (ziv-aflibercept) safe for humans?

Research shows that ziv-aflibercept, which is similar to KHK4951, has been used safely in patients with age-related macular degeneration and other eye conditions, with no adverse events reported in the short term. ^{1 4 6 7 8}

What makes the drug KHK4951 unique for treating age-related macular degeneration?

KHK4951, also known as ziv-aflibercept, is unique because it is an analogue of aflibercept with the same active molecule but in a different buffer solution, offering similar safety and efficacy for improving vision and reducing retinal fluid in age-related macular degeneration. ^{1 2 4 9 10}

Research Team

Sotaro Takigawa

Principal Investigator

Kyowa Kirin Co., Ltd.

Eligibility Criteria

This trial is for adults with active neovascular Age-Related Macular Degeneration (nAMD) affecting the center of their retina. Participants must have certain levels of vision clarity and retinal thickness. Those with extensive eye damage, uncontrolled glaucoma, previous significant eye surgeries or treatments, or other conditions that could affect vision outcomes are excluded.

Inclusion Criteria

You have given your written consent to take part in the study.

My eye condition is due to AMD and affects the center of my vision.

Your best corrected visual acuity score in the study eye was between 73 and 35 letters on the ETDRS chart at baseline.

Exclusion Criteria

I have been treated with IVT anti-VEGF drugs before.

More than half of the lesion in my eye involves bleeding, scarring, or tissue loss and affects the central vision area.

I have active inflammation in my eye.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KHK4951 eye drops in varying doses to assess efficacy and safety

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Aflibercept Injection
• KHK4951

Trial Overview The study is testing the effectiveness and safety of KHK4951 eye drops compared to Aflibercept injections in treating nAMD. The goal is to see if KHK4951 can improve visual function and reduce abnormal blood vessel growth under the retina.

Participant Groups

Group I: Arm C Experimental Treatment 2 Interventions

KHK4951 Low dose

Group II: Arm B Experimental Treatment 2 Interventions

KHK4951 Middle dose

Group III: Arm A Experimental Treatment 2 Interventions

KHK4951 High dose

Aflibercept Injection is already approved in European Union, United States for the following indications:

Approved in European Union as Eylea for:

• Neovascular (wet) age-related macular degeneration
• Macular edema following retinal vein occlusion
• Diabetic macular edema
• Diabetic retinopathy
• Retinopathy of prematurity

Approved in United States as Eylea for:

• Neovascular (wet) age-related macular degeneration
• Macular edema following retinal vein occlusion
• Diabetic macular edema
• Diabetic retinopathy
• Retinopathy of prematurity

Approved in European Union as Zaltrap for:

• Metastatic colorectal cancer

Approved in United States as Zaltrap for:

• Metastatic colorectal cancer

Who Is Running the Clinical Trial?

Kyowa Kirin Co., Ltd.

Lead Sponsor

Trials

181

Recruited

28,800+

Takeyoshi Yamashita

Kyowa Kirin Co., Ltd.

Chief Medical Officer since 2024

Not available

Masashi Miyamoto

Kyowa Kirin Co., Ltd.

Chief Executive Officer

PhD in Molecular Biology

Kyowa Kirin, Inc.

Lead Sponsor

Trials

49

Recruited

5,700+

Findings from Research

A patient with exudative age-related macular degeneration showed significant improvement in visual acuity and reduction of fluid after receiving an intravitreal injection of ziv-aflibercept, indicating its efficacy in treating this condition.

The treatment was well-tolerated with no adverse events reported, demonstrating both short-term safety and effectiveness in managing neovascular macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. de Oliveira Dias, JR., Xavier, CO., Maia, A., et al.[2015]

In a study of 26 patients with neovascular age-related macular degeneration (nv-AMD), intravitreal injections of aflibercept (Eylea) led to a significant improvement in visual acuity over 14 months, with 61.5% of eyes showing improvement and a mean visual acuity change from 0.26 to 0.14 LogMAR (P=0.02).

The treatment also resulted in a significant reduction in central macular thickness from 409μm to 229μm (P<0.02), and no adverse events were reported, indicating that aflibercept is a safe and effective option for treating naïve patients with nv-AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. Papavasileiou, E., Zygoura, V., Richardson, T., et al.[2019]

Aflibercept, a recombinant fusion protein, effectively inhibits VEGF signaling and has been shown to significantly improve visual acuity in patients with macular edema due to central retinal vein occlusion (CRVO) when administered intravitreally at a dose of 2 mg monthly, as demonstrated in clinical trials with significant improvements over sham injections.

The treatment was generally well tolerated with minimal risk of systemic drug accumulation, making aflibercept a safe and effective option for managing CRVO-related macular edema, although optimal monitoring strategies for long-term efficacy still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. Yang, LP., McKeage, K.[2021]

Ziv-aflibercept, an analogue of aflibercept, has shown a similar safety profile to existing treatments for neovascular age-related macular degeneration (nAMD), effectively maintaining or improving best-corrected visual acuity (BCVA) and reducing retinal fluid and central foveal thickness (CFT).

Clinical trials indicate that ziv-aflibercept is also effective in treating other neovascular conditions like diabetic macular edema (DME) and retinal vein occlusion (RVO), but further randomized studies are necessary to confirm its efficacy specifically for nAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept: A Comprehensive Review. Barmas-Alamdari, D., D'Souza, HS., Kapoor, KG., et al.[2019]

In a study of 26 patients with refractory diabetic macular edema (DME), ziv-aflibercept treatment led to significant improvements in visual acuity and macular thickness after switching from previous anti-VEGF therapies.

No adverse ocular or systemic side effects were reported, indicating that ziv-aflibercept is a safe option for patients who did not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. Ashraf, M., Kayal, HE., Souka, AAR.[2022]

A study involving 12 patients showed that a single intravitreal injection of ziv-aflibercept for treating choroidal neovascularization due to age-related macular degeneration was safe, with no serious ocular or systemic adverse events reported after 30 days.

While there was only a slight improvement in best-corrected visual acuity after treatment, the absence of significant side effects suggests that ziv-aflibercept could be a viable low-cost alternative for macular disease therapy, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. Chhablani, J., Narayanan, R., Mathai, A., et al.[2022]

In a study of 60 patients receiving an average of 8.4 intravitreal injections of ziv-aflibercept over a mean follow-up of 9.2 months, significant improvements in best-corrected visual acuity (BCVA) and reductions in central macular thickness (CMT) were observed, indicating the treatment's efficacy for retinal disease.

The treatment was found to be safe, with no significant increases in intraocular pressure, no progression of lens opacities, and only one case of mild transient iritis, suggesting that repeated injections of ziv-aflibercept are well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. Mansour, AM., Ashraf, M., Dedhia, CJ., et al.[2022]

Intravitreal injections of ziv-aflibercept (IVI-ZA) over 48 weeks were found to be safe, with no significant changes in electroretinogram results or any systemic or ocular complications in the seven patients with diabetic macular edema (DME).

The treatment led to a significant improvement in best-corrected visual acuity (BCVA) after the first injection, which was maintained throughout the study, and a notable decrease in central retinal thickness (CRT), indicating its efficacy in managing DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes. de Andrade, GC., de Oliveira Dias, JR., Maia, A., et al.[2019]

In a study comparing 42 eyes treated with aflibercept (IVA) and 56 eyes treated with ranibizumab (IVR) for age-related macular degeneration (AMD), aflibercept showed a statistically significant improvement in visual acuity (VA) at 6 months compared to ranibizumab (p = 0.041).

Despite the better short-term improvement in VA with aflibercept, it was associated with a shorter time to first recurrence and a lower remission maintenance rate compared to ranibizumab, indicating that the type of AMD may influence treatment outcomes more than the choice of medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of 12 Months Outcome of As-needed Intravitreal Aflibercept or Ranibizumab for the Treatment of Naïve Patients with Age-related Macular Degeneration]. Umeda, N., Hokao, K., Tsukahara, T., et al.[2016]

In a study involving 70 Japanese patients with wet age-related macular degeneration, intravitreal aflibercept (IVT-AFL) demonstrated effective vision maintenance and improvement in best-corrected visual acuity (BCVA) after 52 weeks, comparable to ranibizumab.

All treatment groups showed a decrease in central retinal thickness and choroidal neovascularization, with IVT-AFL being well tolerated and having a balanced incidence of ocular adverse events across different dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study. Ogura, Y., Terasaki, H., Gomi, F., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. [2015]

2. Greece pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept: A Comprehensive Review. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

[Comparison of 12 Months Outcome of As-needed Intravitreal Aflibercept or Ranibizumab for the Treatment of Naïve Patients with Age-related Macular Degeneration]. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study. [2022]