VRDN-001 for Thyroid Eye Disease

(STRIVE Trial)

Not currently recruiting at 53 trial locations

Overseen By James Peace, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Viridian Therapeutics, Inc.

Must not be taking: Corticosteroids, Rituximab, Tocilizumab, others

Disqualifiers: Inflammatory bowel disease, Ear pathology, 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: 5

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VRDN-001, an anti-IGF1R monoclonal antibody, for people with thyroid eye disease (TED). TED causes inflammation and swelling around the eyes, and VRDN-001 aims to reduce these symptoms by targeting a specific receptor in the body. The trial will assess the safety and tolerability of this treatment for patients. Those diagnosed with TED who feel the condition affects daily life might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have used systemic corticosteroids within 2 weeks or any other therapy for thyroid eye disease within 8 weeks before the trial begins.

Is there any evidence suggesting that VRDN-001 is likely to be safe for humans?

Research shows that VRDN-001 has been tested on over 100 people, focusing on its safety and tolerability. In these studies, most participants tolerated VRDN-001 well, experiencing no severe side effects.

One study specifically examined individuals with thyroid eye disease (TED) and found that VRDN-001 met all its main safety goals, indicating the treatment did not cause unexpected or serious health problems.

Overall, the evidence suggests VRDN-001 is safe, with manageable side effects. This is encouraging for those considering joining a trial for this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thyroid eye disease?

VRDN-001 is unique because it targets the insulin-like growth factor-1 receptor (IGF-1R), which is a different approach compared to most current treatments for Thyroid Eye Disease like Tepezza. While existing treatments often focus on blocking inflammation, VRDN-001 directly targets and blocks the IGF-1R pathway, potentially reducing the eye symptoms more effectively. Researchers are excited about this treatment because it could offer a more targeted therapy, potentially leading to quicker and more significant improvements for patients.

What evidence suggests that VRDN-001 might be an effective treatment for thyroid eye disease?

Research has shown that VRDN-001, also known as veligrotug, could be a promising treatment for thyroid eye disease (TED). In the largest study of its kind, VRDN-001 achieved all its main goals, indicating it effectively reduces symptoms. This trial will test VRDN-001 in different dosages, with participants receiving either 10 mg/kg or 3 mg/kg. The drug works by blocking a receptor called IGF-1R, which plays a role in the inflammation and swelling common in TED. Earlier results suggest it can significantly decrease these symptoms. Overall, the evidence supports VRDN-001 as a potentially effective treatment for TED. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Thyroid Eye Disease (TED), a condition often associated with Graves' disease. Participants should have active symptoms and be adults who can provide informed consent. Specific details about what makes someone eligible or not are not provided here.

Inclusion Criteria

Must agree to use highly effective contraception method as specified in the protocol

I am not pregnant.

I have been diagnosed with thyroid eye disease and my doctor thinks I could benefit from treatment.

Exclusion Criteria

I haven't had treatments targeting IGF-1R or experimental drugs for TED.

Must not have received an investigational agent for any condition within 8 weeks prior to Day 1

Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the Investigator would confound interpretation of the study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 infusions of VRDN-001 at either 10 mg/kg or 3 mg/kg

5 weeks

5 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

• VRDN-001

Trial Overview The study tests two different doses of VRDN-001, a new drug designed to block a receptor that might cause eye problems in TED. It's given to see if it's safe and how well patients tolerate it compared to existing treatments.

How Is the Trial Designed?

Group I: VRDN-001 10 mg/kg Experimental Treatment 1 Intervention

5 infusions of VRDN-001 10 mg/kg

Group II: 5 infusions of VRDN-001 3 mg/kg Experimental Treatment 1 Intervention

5 infusions of VRDN-001 3 mg/kg

Who Is Running the Clinical Trial?

Viridian Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Published Research Related to This Trial

Teprotumumab (TEPEZZA®) is the first approved therapy for thyroid eye disease (TED) in the USA, showing significant improvements in symptoms like proptosis and overall quality of life in phase II and III trials with adults suffering from moderate-to-severe TED.

The treatment was generally well tolerated, with some adverse effects like muscle spasms and hearing loss, but it maintained clinical benefits for up to 51 weeks after treatment, marking a significant advancement in managing TED symptoms that were previously difficult to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: A Review in Thyroid Eye Disease. Nie, T., Lamb, YN.[2022]

Teprotumumab, used for treating thyroid eye disease, effectively targets the insulin-like growth factor-1 receptor (IGF-1R), but it has been associated with common adverse effects such as hyperglycemia (10%-30% incidence) and hearing changes, which can range from mild ear pressure to hearing loss.

The review highlights the importance of considering these potential risks when using teprotumumab, suggesting that future therapies targeting IGF-1R should address these adverse effects to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Adverse Effects Profile of Teprotumumab. Stan, MN., Krieger, CC.[2023]

Teprotumumab (Tepro) effectively inhibits hyaluronan (HA) production in orbital fibroblasts from patients with thyroid eye disease (TED) by blocking the crosstalk between TSH receptors (TSHR) and IGF1 receptors (IGF1R), which is crucial for the disease's pathogenesis.

The study demonstrated that Tepro does not bind to TSHRs but still reduces HA production stimulated by TSHR/IGF1R crosstalk, indicating that its mechanism of action in treating TED involves disrupting this interaction rather than directly targeting TSHRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease. Krieger, CC., Sui, X., Kahaly, GJ., et al.[2022]

Teprotumumab, an IGF-1R antagonist antibody, has shown efficacy and safety in treating moderate-to-severe thyroid eye disease (TED) in phase 2 and 3 clinical trials, leading to significant improvements in proptosis for patients.

This targeted therapy represents a shift in TED management, as it not only addresses symptoms but also modifies the disease course, potentially improving long-term patient outcomes compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Era in the Treatment of Thyroid Eye Disease. Patel, A., Yang, H., Douglas, RS.[2020]

Teprotumumab, an IGF-1R inhibitor approved for thyroid eye disease, highlights the therapeutic potential of targeting IGF-1 and its receptor, but its systemic effects and local side effects in the eye need careful consideration.

Research shows that IGF-1 influences various ocular processes, including growth, inflammation, and retinal angiogenesis, but more studies are needed to fully understand the implications of anti-IGF-1R treatments on eye health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Insulin-like Growth Factor-1 and Its Receptor in the Eye: A Review and Implications for IGF-1R Inhibition. Truong, T., Silkiss, RZ.[2023]

In a study of 18 patients with thyroid eye disease who did not respond to multiple steroid treatments, Tocilizumab significantly improved disease activity, as shown by a mean reduction of 5.89 points in the Clinical Activity Score (CAS).

Tocilizumab also led to a substantial decrease in thyroid-stimulating immunoglobulin (TSI) levels by 76.18% and improved symptoms such as proptosis and extraocular motility, with no severe side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of active corticosteroid-resistant graves' orbitopathy. Pérez-Moreiras, JV., Alvarez-López, A., Gómez, EC.[2022]

Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, has been shown to significantly improve symptoms of thyroid eye disease (TED) in two clinical trials involving 170 patients, with a responder rate of 69% compared to 20% for placebo in the phase 2 study.

The treatment resulted in a substantial reduction in proptosis (eye bulging) and clinical activity scores, with over half of the responders maintaining their improvement for up to 51 weeks after treatment, although it is associated with some common side effects like muscle spasms and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: Interpreting the Clinical Trials in the Context of Thyroid Eye Disease Pathogenesis and Current Therapies. Winn, BJ., Kersten, RC.[2021]

Teprotumumab significantly reduces proptosis (eye bulging) and inflammation in patients with chronic Thyroid Eye Disease (TED), with an average reduction of 3.5 mm in proptosis after treatment.

In a study of 31 patients who received an average of 7 infusions, 67% of those with diplopia (double vision) experienced a significant improvement, and there was a notable reduction in both muscle and fat tissue volume in the orbits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of chronic thyroid eye disease. Ugradar, S., Kang, J., Kossler, AL., et al.[2022]

Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-I receptor, has shown an 83% response rate in reducing proptosis (eye bulging) in patients with thyroid eye disease, indicating its efficacy in treating this condition.

The treatment is generally well tolerated, with common side effects including muscle spasms, nausea, and fatigue, suggesting that while it is effective, patients should be monitored for these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of thyroid eye disease. Ju, Y., Yang, J.[2021]

Teprotumumab is an effective treatment for thyroid eye disease (TED), showing significant efficacy in reducing inflammation and proptosis in both acute (<2 years) and chronic (>2 years) cases, primarily by decreasing orbital fat and muscle volume.

While teprotumumab is a powerful option for TED, it is associated with side effects such as muscle spasms, hearing loss, and hyperglycemia, and there are concerns about its potential link to inflammatory bowel disease flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface. Ugradar, S., Kossler, AL., Douglas, R., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12545473/

OR31-04 Efficacy and Safety of Veligrotug (VRDN-001), a Full ... OR31-04 Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05176639

NCT05176639 | A Safety, Tolerability and Efficacy Study of ... A Safety, Tolerability and Efficacy Study of Veligrotug (VRDN 001) in Healthy Volunteers and Participants With Thyroid Eye Disease (TED) ( THRIVE ) (THRIVE).

3. investors.viridiantherapeutics.com investors.viridiantherapeutics.com/news/news-details/2024/Viridian-Therapeutics-Announces-Positive-Topline-Results-from-Veligrotug-VRDN-001-Phase-3-THRIVE-Clinical-Trial-in-Patients-with-Active-Thyroid-Eye-Disease/default.aspx

News Details Veligrotug (VRDN-001) achieved all primary and secondary endpoints in THRIVE, the largest phase 3 trial conducted to date of an anti-IGF-1R antibody in thyroid ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10554507/

OR26-02 VRDN-001, A Full Antagonist Antibody To IGF-1 ... VRDN-001, a full antagonist antibody to IGF-1 receptor (IGF-1R), is under development for the treatment of thyroid eye disease (TED).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06021054

NCT06021054 | An Efficacy, Safety, and Tolerability Study ... This is a clinical trial assessing the efficacy, safety, and tolerability of an investigational drug, veligrotug (VRDN-001), in participants with chronic ...

6. investors.viridiantherapeutics.com investors.viridiantherapeutics.com/news/news-details/2021/Viridian-Therapeutics-Announces-First-Subject-Dosed-in-Phase-12-Clinical-Trial-of-VRDN-001-for-Thyroid-Eye-Disease-TED-12-20-2021/default.aspx

News Details The clinical development plan for VRDN-001 was informed by safety, tolerability, pharmacokinetic, and pharmacodynamic data from more than 100 ...

7. db.antibodysociety.org db.antibodysociety.org/db0/1482/

Veligrotug Clinical Naked monospecific ... VRDN-001, an anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody in development for the treatment of thyroid eye disease. Oct. 28, 2020 ...