TOUR006 for Thyroid Eye Disease

(spiriTED Trial)

Recruiting in Palo Alto (17 mi)

+35 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Tourmaline Bio, Inc.

Must not be taking: Teprotumumab, IGF-1 inhibitors, Corticosteroids

Disqualifiers: Sight-threatening complications, Major illness, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests different amounts of a drug called TOUR006 in patients with active inflammation from Thyroid Eye Disease. The goal is to see if it can reduce inflammation and improve symptoms.

Will I have to stop taking my current medications?

The trial requires that you stop using systemic (oral or IV) corticosteroids for conditions other than Thyroid Eye Disease at least 6 weeks before starting the trial. If you have used oral steroids for Thyroid Eye Disease, they must be stopped and completely tapered off at least 6 weeks before the trial begins.

What data supports the effectiveness of the drug TOUR006 for Thyroid Eye Disease?

Research on a similar drug, teprotumumab, which also targets the insulin-like growth factor 1 receptor (IGF-1R), shows it can be effective for treating thyroid eye disease, even in patients with longer disease duration. ^{1 2 3 4 5}

What safety data exists for TOUR006 (PF-04236921) in humans?

There is no specific safety data available for TOUR006 (PF-04236921) in the provided research articles. ^{1 6 7 8 9}

How is the drug TOUR006 different from other treatments for thyroid eye disease?

TOUR006 (PF-04236921) is unique because it may target different pathways or mechanisms compared to existing treatments like teprotumumab, which specifically inhibits the insulin-like growth factor 1 receptor (IGF-1R). This could offer a novel approach to managing thyroid eye disease, especially if it addresses different aspects of the disease's progression or symptoms. ^{1 8 9 10 11}

Research Team

Clinical Trials

Principal Investigator

Tourmaline Bio

Eligibility Criteria

This trial is for adults aged 18-75 with moderate to severe active Thyroid Eye Disease (TED) linked to Graves' disease. Participants must have had TED symptoms start within the last year, a certain level of eye protrusion, and elevated thyroid stimulating immunoglobulin. Those with major illnesses or conditions that could risk their health or skew results, pregnant or breastfeeding individuals, recent systemic steroid users for non-TED conditions, and anyone who has used specific TED treatments are excluded.

Inclusion Criteria

My eye bulges more than 3 mm beyond what's normal for my race and gender.

Your blood test shows high levels of thyroid stimulating immunoglobulin.

I have been diagnosed with Graves' disease and have moderate to severe eye problems.

Exclusion Criteria

I have never been treated with teprotumumab or drugs targeting the IGF-1 receptor.

I have not used systemic corticosteroids for non-TED conditions in the last 3 months.

Any other condition that, in the opinion of the investigator, would impair the ability of the participant to comply with the study procedures or impair the ability to interpret data from the participant's participation in the study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive subcutaneous injections of TOUR006 or placebo every 8 weeks for a total of three injections

16 weeks

3 visits (in-person)

Treatment Part B

Participants continue treatment based on proptosis response and rescue therapy use

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TOUR006 (Monoclonal Antibodies)

Trial Overview The study tests TOUR006 at doses of 20mg and 50mg against a placebo in patients with active inflammatory phase of TED. The drug is given as an under-the-skin injection every eight weeks. It's designed to see if TOUR006 can safely improve the condition compared to not receiving the active drug.

Participant Groups

Group I: TOUR006 - 50 MG Experimental Treatment 1 Intervention

In part A of the study, participants will receive a total of three 50 mg subcutaneous injections: 1 injection every 8 weeks (Day 1, Week 8, Week 16) followed by treatment in part B of the study based on proptosis response and rescue therapy use.

Group II: TOUR006 - 20 MG Experimental Treatment 1 Intervention

In part A of the study, participants will receive a total of three 20 mg subcutaneous injections: 1 injection every 8 weeks (Day 1, Week 8, Week 16) followed by treatment in part B of the study based on proptosis response and rescue therapy use.

Group III: Placebo Placebo Group 1 Intervention

In part A of the study, participants will receive a total of three Placebo subcutaneous injections: 1 injection every 8 weeks (Day 1, Week 8, Week 16) followed by treatment in part B of the study based on proptosis response and rescue therapy use.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Site - 0108 Louisville, KY

Site - 0113 Morgantown, WV

Site - 0114 San Diego, CA

Site - 0104 Chapel Hill, NC

More Trial Locations

Who Is Running the Clinical Trial?

Tourmaline Bio, Inc.

Lead Sponsor

Trials

2

Recruited

220+

Findings from Research

Teprotumumab, an IGF-1R inhibitor approved for thyroid eye disease (TED), has shown effectiveness in improving symptoms like proptosis and diplopia even in patients with long-standing disease or those who have not responded to previous treatments.

Recent reports suggest that teprotumumab can benefit patients regardless of disease duration or inflammation markers, indicating its potential as a versatile treatment option for TED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. Subramanian, PS., Cho, RI., Kahana, A.[2023]

In a study of 156 patients with active, untreated thyroid eye disease, those aged 46-70 showed significantly higher clinical activity scores (CAS) compared to younger patients (18-45), indicating more severe symptoms.

Older patients (46-70 years) experienced more conjunctival redness and chemosis, which contributed to their higher CAS scores, suggesting that age may influence the severity of thyroid eye disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Patient Age and the Thyroid Eye Disease-Clinical Activity Score. North, VS., Zhou, HW., Tran, AQ., et al.[2023]

In a study of 303 patients with thyroid eye disease (TED), the demographics and clinical characteristics were similar between those with hyperthyroidism (Hr-TED) and primary hypothyroidism (Ho-TED), indicating that both conditions lead to comparable forms of eye disease.

However, patients with Hr-TED had a significantly longer duration of thyroid disease (49.6 months) compared to those with Ho-TED (22.7 months), suggesting that the progression of thyroid disease may differ between these two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthyroid vs hypothyroid eye disease: the same severity and activity. Kashkouli, MB., Pakdel, F., Kiavash, V., et al.[2022]

Recent advances in treating thyroid eye disease (TED) include the use of selenium, which appears to limit disease progression in mild cases without significant side effects.

Biological immunosuppressive agents have shown effectiveness in managing moderate-to-severe TED, offering long-lasting effects that may reduce recurrence and the need for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Graves disease: advances in treatment of mild, moderate and severe thyroid eye disease. Strianese, D.[2022]

Thyroid eye disease (TED) was found to have a prevalence of 0.09% in a large cross-sectional analysis of 41,211 patients, with the highest rates observed in women and individuals aged 50-59 years.

Factors associated with TED included female sex, older age, smoking status, and Type 1 diabetes, highlighting the need for further investigation into how these factors influence TED across different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid Eye Disease and its Vision-Threatening Manifestations in the Academy IRIS Registry: 2014-2018. Ramesh, S., Zhang, QE., Sharpe, J., et al.[2023]

Teprotumumab treatment in a 51-year-old female with refractory thyroid eye disease led to significant improvements, including resolution of optic neuropathy and a decrease in proptosis measurements after eight infusions.

The case suggests that teprotumumab may be effective in modifying the disease even in advanced cases of thyroid eye disease, as evidenced by reduced extraocular muscle size and improved clinical activity scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab in advanced reactivated thyroid eye disease. Cheng, OT., Schlachter, DM.[2022]

Teprotumumab is the first FDA-approved medication for treating thyroid eye disease (TED) and has shown efficacy in two randomized, double-masked, placebo-controlled trials, with favorable outcomes also reported in post-approval cases.

While teprotumumab is effective, it should be avoided during pregnancy and may exacerbate conditions like inflammatory bowel disease, worsen hyperglycemia, and cause hearing impairment, necessitating careful monitoring of at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease. Teo, HM., Smith, TJ., Joseph, SS.[2021]

Teprotumumab was effective in resolving compressive optic neuropathy (CON) associated with thyroid eye disease (TED) in two patients who did not respond to initial intravenous corticosteroid therapy.

Both patients showed significant clinical improvement and complete resolution of visual field defects early in their treatment with teprotumumab, suggesting it may be a superior option compared to traditional corticosteroid treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: A report of two cases. Chiou, CA., Reshef, ER., Freitag, SK.[2022]

A 67-year-old woman developed thyroid-associated ophthalmopathy (TAO) after receiving radioactive iodine therapy for metastatic thyroid cancer, highlighting a potential complication of RAI therapy.

Treatment with sorafenib and lenvatinib led to a gradual decrease in thyroid-related antibodies and improvement in TAO symptoms, suggesting these medications may help manage TAO without the need for additional ophthalmologic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid-Associated Ophthalmopathy after Radioactive Iodine Therapy for Metastatic Follicular Thyroid Carcinoma. Murayama, D., Toda, S., Okubo, Y., et al.[2021]

In a study of 319 patients with thyroid eye disease (TED), 31% developed superior limbic keratoconjunctivitis (SLK), with several risk factors identified, including younger age, smoking, and the presence of the Graefe sign.

Key clinical indicators such as high Hertel exophthalmometric values, shorter Schirmer's test results, and shorter tear break-up time (TBUT) were significantly associated with an increased risk of developing SLK in TED patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for development of superior limbic keratoconjunctivitis in thyroid eye disease in Japanese. Takahashi, Y., Vaidya, A., Kakizaki, H.[2023]

In a study of 20 patients with thyroid-associated ophthalmopathy (TAO), those with chorioretinal folds (CRFs) exhibited significantly worse visual function and decreased microvascular densities in the macula and radial peripapillary capillaries compared to those without CRFs.

The findings suggest that decreased microvascular density in TAO patients with CRFs is associated with poorer visual outcomes, indicating that CRFs may serve as a warning sign for potentially serious visual impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macular and peripapillary optical coherence tomography angiography metrics in thyroid-associated ophthalmopathy with chorioretinal folds. Zeng, P., Wang, J., Tian, P., et al.[2023]

References

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

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. [2023]

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

Association of Patient Age and the Thyroid Eye Disease-Clinical Activity Score. [2023]

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

Hyperthyroid vs hypothyroid eye disease: the same severity and activity. [2022]

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

Update on Graves disease: advances in treatment of mild, moderate and severe thyroid eye disease. [2022]

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

Thyroid Eye Disease and its Vision-Threatening Manifestations in the Academy IRIS Registry: 2014-2018. [2023]

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

Teprotumumab in advanced reactivated thyroid eye disease. [2022]

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

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease. [2021]

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

Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: A report of two cases. [2022]

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

Thyroid-Associated Ophthalmopathy after Radioactive Iodine Therapy for Metastatic Follicular Thyroid Carcinoma. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Risk factors for development of superior limbic keratoconjunctivitis in thyroid eye disease in Japanese. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Macular and peripapillary optical coherence tomography angiography metrics in thyroid-associated ophthalmopathy with chorioretinal folds. [2023]