KHK4951 for Diabetic Macular Edema

Recruiting at 96 trial locations

Overseen By Ketan Laud

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kyowa Kirin, Inc.

Must not be taking: Corticosteroids, Anti-VEGF, Ozurdex, Iluvien

Disqualifiers: Proliferative diabetic retinopathy, Glaucoma, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with DME.

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, it does list certain eye treatments that should not have been used recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug KHK4951 for Diabetic Macular Edema?

Research shows that ziv-aflibercept, a component of KHK4951, is effective in treating macular edema (swelling in the eye) related to branch retinal vein occlusion, suggesting potential benefits for similar eye conditions like diabetic macular edema. ^{1 2 3 4 5}

What safety data exists for aflibercept in treating macular edema?

Aflibercept has been studied for safety in treating macular edema related to central retinal vein occlusion, and it is generally considered safe in clinical practice. The research indicates that it is well-tolerated by patients, with safety data supporting its use in this condition. ^{2 3 6 7 8}

Research Team

Sotaro Takigawa

Principal Investigator

Kyowa Kirin Co., Ltd.

Eligibility Criteria

This trial is for patients with Diabetic Macular Edema (DME) who have a certain level of central retinal thickness and visual acuity, controlled diabetes (HbA1c ≤ 11%), and no history of severe eye conditions or treatments that could affect the study's outcome.

Inclusion Criteria

Voluntary written informed consent to participate in the study

500 μm ≥ CST ≥ 325 μm in the study eye at screening

BCVA ETDRS letter score of 73 letters to 35 letters as measured by the ETDRS visual acuity chart in the study eye at screening

Exclusion Criteria

My study eye shows signs of worsening diabetic eye disease.

I have had rubeosis in my eye being studied.

My glaucoma in one eye is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Aflibercept Injection
• KHK4951

Trial Overview The trial is testing KHK4951 eye drops against Aflibercept injections to see which one is better at treating DME. Patients will be closely monitored to measure the effectiveness and safety of the KHK4951 treatment.

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

KHK4951 is already approved in United States, European Union for the following indications:

Approved in United States as FOTIVDA for:

• Renal cell carcinoma

Approved in European Union as Fotivda for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Kyowa Kirin, Inc.

Lead Sponsor

Trials

49

Recruited

5,700+

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

Findings from Research

In a study of 35 patients over 24 months, intravitreal bevacizumab (IVB) treatment led to complete resolution of macular edema in 34.3% of cases, indicating its efficacy in managing this condition due to branch retinal vein occlusion (BRVO).

While visual acuity improved significantly in 23% of patients, a median of six injections was needed to achieve and maintain these benefits, highlighting the need for ongoing treatment and further research to compare IVB with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty-Four-Month Results of Intravitreal Bevacizumab in Macular Edema Secondary to Branch Retinal Vein Occlusion. Tsagkataki, M., Papathomas, T., Lythgoe, D., et al.[2016]

Intravitreal ranibizumab (IVR) 0.5 mg significantly improved visual acuity and reduced central foveal thickness compared to non-anti-VEGF treatments, with a notable increase in patients gaining 15 or more letters on the ETDRS scale after six months.

IVR 0.3 mg was found to be equally effective as IVR 0.5 mg in treating macular edema secondary to retinal vein occlusion, indicating that a lower dose may be sufficient for similar therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranibizumab for macular edema secondary to retinal vein occlusion: a meta-analysis of dose effects and comparison with no anti-VEGF treatment. Song, WT., Xia, XB.[2022]

Intravitreal aflibercept (IVA) significantly reduced central macular thickness and improved best-corrected visual acuity in patients with macular edema due to branch retinal vein occlusion, regardless of whether they were treatment-naïve or switched from ranibizumab.

Both treatment groups showed positive outcomes at 1 week and 1 month post-injection, indicating that IVA is an effective short-term treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term outcomes in patients with branch retinal vein occlusion who received intravitreal aflibercept with or without intravitreal ranibizumab. Sakanishi, Y., Usui-Ouchi, A., Tamaki, K., et al.[2020]

In a study of 12 patients with macular edema due to branch retinal vein occlusion, intravitreal bevacizumab (IVB) injections significantly improved visual acuity and reduced central macular thickness over a mean follow-up of 9.8 months.

No ocular or systemic side effects were reported, indicating that IVB is a safe and effective treatment option for managing macular edema associated with BRVO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal bevacizumab for macular oedema secondary to branch retinal vein occlusion. Gündüz, K., Bakri, SJ.[2015]

In a study comparing intravitreal bevacizumab (IVB) and ziv-aflibercept (IVZ) for treating macular edema after branch retinal vein occlusion, both treatments showed similar improvements in visual acuity and central macular thickness over 12 months.

However, IVZ required significantly fewer injections and clinic visits than IVB, suggesting it may be a more cost-effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab versus ziv-aflibercept in branch retinal vein occlusion. Braimah, IZ., Singh, SR., Uplanchiwar, B., et al.[2020]

Aflibercept has been shown to be effective in treating macular edema following central retinal vein occlusion (CRVO), with 56% and 60% of patients achieving significant visual improvement in two major trials (COPERNICUS and GALILEO) compared to much lower rates in control groups.

The drug is well-tolerated and has a higher potency and longer duration of action compared to other anti-VEGF treatments, making it a promising option for patients with CRVO-related macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion. Evoy, KE., Abel, SR.[2022]

In a study of 377 patients treated with intravitreal aflibercept (IVT-AFL) for macular edema due to central retinal vein occlusion (CRVO), the treatment showed a favorable safety profile with only 5.84% experiencing adverse events over 24 months.

The treatment led to significant improvements in best corrected visual acuity (BCVA) and central retinal thickness (CRT), although the degree of improvement was less than that seen in randomized controlled trials, suggesting potential undertreatment in the clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data on Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 24-Month Outcomes. Shimura, M., Fukumatsu, M., Tsujimura, J., et al.[2022]

In a study of 75 participants with macular edema due to branch retinal vein occlusion, both intravitreal bevacizumab and ranibizumab significantly improved visual acuity after 6 months, with gains of +15.6 and +18.1 letters respectively, indicating both treatments are effective.

There was no significant difference in visual gains or central retinal thickness reductions between the two treatments, suggesting that bevacizumab is as effective as ranibizumab for this condition, with a similar safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-masked, controlled study of the efficacy and safety of intravitreal bevacizumab versus ranibizumab in the treatment of macular oedema due to branch retinal vein occlusion: MARVEL Report No. 1. Narayanan, R., Panchal, B., Das, T., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Twenty-Four-Month Results of Intravitreal Bevacizumab in Macular Edema Secondary to Branch Retinal Vein Occlusion. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Ranibizumab for macular edema secondary to retinal vein occlusion: a meta-analysis of dose effects and comparison with no anti-VEGF treatment. [2022]

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

Short-term outcomes in patients with branch retinal vein occlusion who received intravitreal aflibercept with or without intravitreal ranibizumab. [2020]

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

Intravitreal bevacizumab for macular oedema secondary to branch retinal vein occlusion. [2015]

5. India pubmed.ncbi.nlm.nih.gov

Bevacizumab versus ziv-aflibercept in branch retinal vein occlusion. [2020]

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

Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion. [2022]

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

Real-World Data on Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 24-Month Outcomes. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A randomised, double-masked, controlled study of the efficacy and safety of intravitreal bevacizumab versus ranibizumab in the treatment of macular oedema due to branch retinal vein occlusion: MARVEL Report No. 1. [2022]