VRDN-001 for Thyroid Eye Disease

(THRIVE Trial)

Recruiting at 59 trial locations

Overseen By Kimberly Cockerham

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Viridian Therapeutics, Inc.

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

Disqualifiers: Diabetes, Renal impairment, Inflammatory bowel, 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: 6 weeks for TED MAD participants, 15 weeks for Phase 3 participants

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing VRDN-001, a medicine that blocks a part of cells causing inflammation, in patients with thyroid eye disease. The goal is to see if it can reduce eye swelling and inflammation.

Will I have to stop taking my current medications?

The trial requires that you stop using systemic corticosteroids at least 2 to 4 weeks before starting, and you must not have taken rituximab, tocilizumab, or other immunosuppressive agents within 8 to 12 weeks prior. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug VRDN-001 for Thyroid Eye Disease?

Teprotumumab, a similar drug that targets the same IGF-1 receptor, has been shown in clinical trials to significantly improve symptoms of Thyroid Eye Disease, such as reducing eye bulging and improving overall response rates. This suggests that VRDN-001, which also targets the IGF-1 receptor, may have similar potential benefits for patients with this condition. ^{1 2 3 4 5}

Is VRDN-001 safe for humans?

VRDN-001, also known as an anti-IGF1R monoclonal antibody, is similar to teprotumumab, which has been approved for thyroid eye disease. While teprotumumab has shown some side effects due to its action on the IGF-1 receptor, the safety data from its trials can provide some reassurance about the general safety of this class of drugs. ^{1 3 4 6 7}

How is the drug VRDN-001 different from other treatments for thyroid eye disease?

VRDN-001 is unique because it is an anti-IGF1R monoclonal antibody, similar to teprotumumab, which targets the insulin-like growth factor-1 receptor (IGF-1R) to potentially halt or slow the progression of thyroid eye disease without surgery. This approach is based on the understanding that IGF-1R plays a role in the disease's development. ^{1 3 8 9 10}

Research Team

Thomas Ciulla, MD, MBA

Principal Investigator

Viridian Therapeutics, Inc.

Eligibility Criteria

This trial is for healthy individuals and those with Thyroid Eye Disease (TED), specifically moderate to severe cases. Participants should not have certain medical conditions like diabetes, recent kidney issues, or hearing loss. They must not have used specific medications recently and agree to use effective contraception.

Inclusion Criteria

I am not able to become pregnant.

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

Your eye condition must be rated as at least a 3 on a 7-point scale for the study.

Exclusion Criteria

I have never been treated with anti-IGF-1R monoclonal antibody.

I haven't taken rituximab, tocilizumab, or similar drugs in the last 8 weeks.

I haven't taken oral steroids in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two intravenous infusions of veligrotug (VRDN-001) or placebo

6 weeks for TED MAD participants, 15 weeks for Phase 3 participants

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VRDN-001

Trial Overview The study tests VRDN-001, a monoclonal antibody targeting the IGF-1R receptor which could reduce inflammation in TED patients. It's being compared against a placebo in different phases of trials to assess safety, tolerability, and how it's processed by the body.

Participant Groups

Group I: Phase 3 Cohort (THRIVE) Experimental Treatment 2 Interventions

Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.

Group II: Phase 1/2 MAD (HV and TED) Experimental Treatment 1 Intervention

Healthy volunteers and participants with TED will be randomized to receive two intravenous infusions of veligrotug (VRDN-001) or placebo with an interval of 3

Who Is Running the Clinical Trial?

Viridian Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Findings from Research

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, 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]

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 (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, 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]

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]

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, 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, 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]

References

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

A New Era in the Treatment of Thyroid Eye Disease. [2020]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of chronic thyroid eye disease. [2022]

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

Treatment of active corticosteroid-resistant graves' orbitopathy. [2022]

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

Teprotumumab: A Review in Thyroid Eye Disease. [2022]

6. United States 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. [2023]

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

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface. [2022]

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

Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of thyroid eye disease. [2021]

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

The Adverse Effects Profile of Teprotumumab. [2023]