Tarcocimab + Tabirafusp for Wet Age-Related Macular Degeneration

(DAYBREAK Trial)

Recruiting at 71 trial locations

Overseen By Kodiak Sciences Inc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Kodiak Sciences Inc

Disqualifiers: Monocular, Fibrosis, Atrophy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants with Neovascular (Wet) Age-related Macular Degeneration (wAMD)

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug Tarcocimab + Tabirafusp different from other treatments for wet age-related macular degeneration?

Tarcocimab + Tabirafusp is unique because it combines two components, Tarcocimab Tedromer and Tabirafusp Tedromer, which may offer a novel approach to treating wet age-related macular degeneration by potentially targeting different pathways involved in the disease. This combination could provide a new option compared to the standard anti-angiogenesis therapies currently used for this condition. ^{1 2 3 4 5}

Research Team

Pablo Velazquez-Martin, MD

Principal Investigator

Kodiak Sciences Inc

Eligibility Criteria

This trial is for individuals with wet age-related macular degeneration (wAMD). Specific eligibility criteria are not provided, but typically participants would need a confirmed diagnosis of wAMD and meet certain health standards.

Inclusion Criteria

I have a specific type of untreated eye condition related to AMD that affects my vision.

BCVA ETDRS score between 78 and 25 letters (Snellen equivalent ~20/32 and 20/320) inclusive, in the Study Eye at screening and reconfirmed at Day 1

I am able to understand and sign the consent form.

Exclusion Criteria

My vision in my non-study eye is very poor or I only have one eye.

Over half of the lesion in my eye is scarred or has thinned, affecting the central vision area.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravitreal injections of study drugs with varying schedules: Tabirafusp tedromer every 4 weeks for 4 doses, then every 8 weeks or individualized; Tarcocimab tedromer every 4 weeks for 4 doses, then individualized every 4 to 24 weeks; Aflibercept every 4 weeks for 3 doses, then every 8 weeks.

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tabirafusp Tedromer (Monoclonal Antibodies)
• Tarcocimab Tedromer (Monoclonal Antibodies)

Trial Overview The study tests the effectiveness and safety of two drugs, Tarcocimab Tedromer and Tabirafusp Tedromer, against Aflibercept in treating wAMD. It's likely that patients will be randomly assigned to receive one of these treatments.

Participant Groups

Group I: Tarcocimab tedromer 5 mg (KSI-301) Experimental Treatment 1 Intervention

Intravitreal injection of tarcocimab tedromer once every 4 weeks for 4 monthly doses followed by individualized dosing every 4 to 24 weeks.

Group II: Tabirafusp tedromer 5 mg (KSI-501) Experimental Treatment 1 Intervention

Intravitreal injection of tabirafusp tedromer once every 4 weeks for 4 monthly doses followed by every-8-week dosing with additional individualized dosing (up to monthly dosing)

Group III: Aflibercept 2 mg Active Control 1 Intervention

Intravitreal injection of aflibercept once every 4 weeks for 3 monthly doses followed by every-8-week dosing

Who Is Running the Clinical Trial?

Kodiak Sciences Inc

Lead Sponsor

Trials

9

Recruited

3,900+

Findings from Research

Emerging treatments for dry age-related macular degeneration (AMD) focus on two main strategies: preventing cell loss through neuroprotection and oxidative damage prevention, and suppressing inflammation.

Current and potential therapies include neuroprotective drugs, micronutrient supplementation, visual cycle modulators, and anti-inflammatory agents, suggesting a combination approach may be most effective in managing AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches and potential treatments for dry age-related macular degeneration. Damico, FM., Gasparin, F., Scolari, MR., et al.[2022]

Eliminating senescent retinal pigment epithelium (RPE) cells may offer a new treatment strategy for age-related macular degeneration (AMD), particularly for the dry form, which currently has no FDA-approved therapies.

Using the MDM2-p53 inhibitor Nutlin-3a to clear these senescent cells showed promising results in reducing retinal degeneration in animal models, suggesting a novel approach to address both neovascular and dry AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting senescent retinal pigment epithelial cells facilitates retinal regeneration in mouse models of age-related macular degeneration. Chae, JB., Jang, H., Son, C., et al.[2022]

Emixustat and lampalizumab are two promising new classes of medications being studied for the treatment of dry age-related macular degeneration (AMD), with both showing positive results in phase 2 clinical trials.

Lampalizumab is currently undergoing a large phase 3 clinical trial, focusing on its effectiveness against geographic atrophy, a severe form of dry AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emixustat and Lampalizumab: Potential Therapeutic Options for Geographic Atrophy. Jack, LS., Sadiq, MA., Do, DV., et al.[2018]

Visual cycle modulators, specifically emixustat and fenretinide, show limited efficacy in treating geographic atrophy due to age-related macular degeneration (AMD), with no significant improvement in visual acuity or disease progression compared to placebo in three randomized controlled trials involving 821 participants.

Both drugs were associated with ocular adverse effects, such as delayed dark adaptation and chromatopsia, which led to study dropouts, highlighting the need for further investigation into their safety and efficacy in larger, focused studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual cycle modulators versus placebo or observation for the prevention and treatment of geographic atrophy due to age-related macular degeneration. Yeong, JL., Loveman, E., Colquitt, JL., et al.[2021]

Age-related macular degeneration (AMD) is a leading cause of blindness in older adults, characterized by the loss of photoreceptor and retinal pigment epithelial cells in the macula, and is influenced by both genetic and environmental factors.

The paper reviews various pharmacological therapies for the wet form of AMD, highlighting new drugs in research that target the disease's underlying angiogenesis and inflammatory processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies. Shams Najafabadi, H., Daftarian, N., Ahmadieh, H., et al.[2018]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

New approaches and potential treatments for dry age-related macular degeneration. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting senescent retinal pigment epithelial cells facilitates retinal regeneration in mouse models of age-related macular degeneration. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Emixustat and Lampalizumab: Potential Therapeutic Options for Geographic Atrophy. [2018]

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

Visual cycle modulators versus placebo or observation for the prevention and treatment of geographic atrophy due to age-related macular degeneration. [2021]

5. Iran pubmed.ncbi.nlm.nih.gov

Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies. [2018]