Tarcocimab + Tabirafusp for Wet Age-Related Macular Degeneration

(DAYBREAK Trial)

Not currently recruiting at 77 trial locations

Overseen By Kodiak Sciences Inc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kodiak Sciences Inc

Disqualifiers: Monocular, Fibrosis, Atrophy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for wet age-related macular degeneration (wAMD), a condition that affects eyesight as people age. The study evaluates the effectiveness and safety of two new drugs, Tarcocimab Tedromer and Tabirafusp Tedromer, compared to Aflibercept, a current treatment. Suitable candidates for this trial are those who have never received treatment for their wAMD and experience changes in central vision due to abnormal blood vessel growth in the retina. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants a chance to contribute to the development of potentially groundbreaking treatments.

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.

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

Research has shown that both tabirafusp tedromer and tarcocimab tedromer have promising safety results from earlier studies. Early trials found tabirafusp tedromer to be safe and effective in maintaining or improving vision over two years for people with wet age-related macular degeneration (AMD). Most patients did not need frequent doses, indicating good tolerance.

For tarcocimab tedromer, studies found no significant difference in cataract development between patients treated with tarcocimab and those receiving the standard treatment, aflibercept. This balance in side effects is a positive sign of safety.

Since this trial is in a later stage, both treatments have likely already demonstrated a good safety profile in earlier trials. They have been tested in smaller groups before being used in larger groups to ensure safety for more people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for wet age-related macular degeneration, which typically involve regular injections like aflibercept, tabirafusp tedromer and tarcocimab tedromer stand out for their potential to reduce injection frequency. Both treatments use a unique approach by delivering them intravitreally with the possibility of extending the intervals between doses after initial monthly administrations. Researchers are excited about these therapies because they could offer patients a more convenient treatment schedule, potentially improving adherence and overall outcomes.

What evidence suggests that this trial's treatments could be effective for wet age-related macular degeneration?

This trial will compare Tabirafusp Tedromer and Tarcocimab Tedromer as separate treatments for wet age-related macular degeneration (wAMD). Research has shown that both treatments are promising. Participants who received Tarcocimab Tedromer experienced better results, requiring fewer eye injections. For those receiving Tabirafusp Tedromer, new dosing schedules are under development to potentially extend the time between doses. These treatments are compared to Aflibercept, a common wAMD treatment, to evaluate their effectiveness and safety. Early results suggest these new treatments might perform as well as or better than current options, with less frequent dosing. ^{1 2 3 6 7}

Who Is on the Research Team?

Pablo Velazquez-Martin, MD

Principal Investigator

Kodiak Sciences Inc

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tabirafusp Tedromer
• Tarcocimab Tedromer

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.

How Is the Trial Designed?

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

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

Approved in United States as Kimmtrak for:

• Unresectable or metastatic uveal melanoma in HLA-A*02:01-positive adults

Approved in European Union as Kimmtrak for:

• Unresectable or metastatic uveal melanoma in HLA-A*02:01-positive adults

Who Is Running the Clinical Trial?

Kodiak Sciences Inc

Lead Sponsor

Trials

9

Recruited

3,900+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06556368

NCT06556368 | A Study to Evaluate the Efficacy and ... A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer ... (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK (DAYBREAK).

2. brightfocus.org brightfocus.org/resource/emerging-treatments-offer-new-hope-for-dry-and-wet-age-related-macular-degeneration/

Emerging Treatments Offer New Hope for Dry and Wet Age ... New treatment strategies in development aim to reduce the need for frequent eye injections in wet age-related macular degeneration (AMD). Gene ...

3. guidelinecentral.com guidelinecentral.com/clinical-trial/?id=NCT06556368

A Study to Evaluate the Efficacy and Safety of Tarcocimab ... A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age- ...

4. kodiak.com kodiak.com/our-pipeline/

Our Pipeline Across tarcocimab tedromer pivotal studies for diabetic retinopathy, retinal vein occlusion and wet age-related macular degeneration. ... outcomes in wet AMD and ...

5. withpower.com withpower.com/trial/phase-3-macular-degeneration-7-2024-aa0a1

Tarcocimab + Tabirafusp for Wet Age-Related Macular ... Trial Overview The study tests the effectiveness and safety of two drugs, Tarcocimab Tedromer and Tabirafusp Tedromer, against Aflibercept in treating wAMD.

6. kodiak.com kodiak.com/our-pipeline-pre-march4-2025/

Our Pipeline (Version Pre March 4, 2025) Across tarcocimab tedromer pivotal studies for diabetic retinopathy, retinal vein occlusion and wet age-related macular degeneration. 2 ...

7. trial.medpath.com trial.medpath.com/clinical-trial/966db2b8ff961868/nct06556368-efficacy-safety-tarcocimab-tabirafusp-aflibercept-wamd

A Study to Evaluate the Efficacy and Safety of Tarcocimab ... A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age- ...