KHK4951 for Diabetic Macular Edema

Not currently recruiting at 115 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests eye drops called KHK4951 (also known as Tivozanib) to evaluate their effectiveness and safety in treating diabetic macular edema (DME), a condition that causes blurry vision due to fluid build-up in the eye. Researchers will divide participants into three groups to receive different doses of the eye drops to determine the most effective dose. Individuals with DME who experience vision problems may qualify for this trial, provided they haven't recently undergone certain eye treatments or surgeries. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found no major safety concerns with tivozanib eye drops, also known as KHK4951. People who used the eye drops generally did not experience serious problems. This trial is a phase 2 study, building on earlier research that tested the eye drops' safety in healthy people. That research showed the eye drops did not cause serious side effects. While this is encouraging, further testing is necessary to confirm their safety for people with diabetic macular edema (DME). ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for diabetic macular edema, like anti-VEGF injections, work by reducing blood vessel leakage and swelling in the retina. But KHK4951 is unique because it targets different pathways, potentially offering an alternative for patients who don't respond well to standard therapies. Researchers are excited about KHK4951 because it is being tested in varying doses—high, middle, and low—which might help fine-tune its effectiveness and minimize side effects. This could lead to a more personalized approach to treating diabetic macular edema, providing hope for improved vision outcomes.

What evidence suggests that KHK4951 might be an effective treatment for diabetic macular edema?

Research is testing KHK4951 eye drops for diabetic macular edema (DME), a condition that causes swelling in the part of the eye affecting vision. Participants in this trial will receive different doses of KHK4951 to evaluate its safety and effectiveness. Early studies have shown that a similar drug, tivozanib, is safe for healthy individuals and those with neovascular age-related macular degeneration (nAMD). This suggests that KHK4951 might also be safe for people with DME. Although direct evidence of KHK4951's effectiveness for DME is not yet available, it targets abnormal blood vessel growth, a common issue in DME. Further research is needed to confirm these potential benefits. ^{1 2 3 4 6}

Who Is on the Research Team?

Sotaro Takigawa

Principal Investigator

Kyowa Kirin Co., Ltd.

Are You a Good Fit for This Trial?

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.

My glaucoma in one eye is not under control.

I have had rubeosis in my eye being studied.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

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 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]

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]

Citations

1. kkna.kyowakirin.com kkna.kyowakirin.com/media-center/kyowa-kirin-announces-first-patient-enrolled-in-the-phase-2-clinical-trial-evaluating-tivozanib-eye-drops-in-patients-with-diabetic-macular-edema/

Kyowa Kirin Announces First Patient Enrolled in the Phase ... This study investigates the efficacy and safety of KHK4951 in patients with diabetic macular edema (DME).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06116916

NCT06116916 | Study to Assess the Efficacy & Safety of ... The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with DME. Official Title. A Phase 2, Multicenter, Randomized, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666914524000897

Phase I Study of Tivozanib Eye Drops in Healthy ... Tivozanib eye drops showed a favorable safety profile in healthy Japanese and White men and Japanese patients with nAMD.

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/490162

Study to Assess the Efficacy & Safety of KHK4951 in Patients ... The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with DME.

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/kyowa-kirin-dme-trial/

Kyowa Kirin enrols first subject in Phase II diabetic macular ... The trial aims to assess the safety and efficacy of KHK4951 in patients with DME across multiple countries, including the US, Japan, Australia, ...

6. ophthalmologytimes.com ophthalmologytimes.com/view/kyowa-kirin-enrolls-first-patient-in-phase-2-trial-of-drops-for-treatment-of-diabetic-macular-edema

Kyowa Kirin enrolls first patient in phase 2 trial of drops for ... Kyowa Kirin has announced the enrollment of the first patient in its phase 2 trial evaluating tivozanib eye drops (KHK4951) in patients with diabetic macular ...