VRDN-001 for Thyroid Eye Disease

(STRIVE Trial)

Recruiting at 51 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

231 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigational drug, VRDN-001, is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in patients with thyroid eye disease (TED). The primary objective of this clinical trial is to evaluate the safety and tolerability of VRDN-001 in patients with TED.

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.

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 benefits. ^{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 it can have some side effects due to its action on the IGF-1 receptor, it has been studied in humans, and its safety profile is being evaluated in clinical trials. ^{2 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. ^{2 4 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 (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

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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]