TOUR006 for Thyroid Eye Disease

(spiriTED Trial)

Recruiting at 89 trial locations

Overseen By Tourmaline Bio

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tourmaline Bio, Inc.

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

Disqualifiers: Sight-threatening complications, Major illness, others

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

Compensation: Varies

Number of Visits: 3

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, TOUR006, for individuals with Thyroid Eye Disease (TED), which causes eye pain and bulging. Researchers aim to determine if two different doses of TOUR006 are more effective than a placebo in reducing these symptoms. Participants will receive injections every eight weeks and will be monitored for changes in their condition. Ideal candidates include those with Graves' disease who have experienced active TED symptoms, such as significant eye bulging, within the last 15 months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that TOUR006 is likely to be safe for humans?

Research has shown that TOUR006 is a fully-human antibody designed to block IL-6, a protein involved in inflammation. This treatment is intended to remain in the body longer, potentially reducing the number of doses needed. However, specific safety information for TOUR006 in humans remains limited. Trials are currently testing its safety and effectiveness for people with Thyroid Eye Disease (TED).

As TOUR006 is in an early trial stage, researchers are still collecting safety data. This phase focuses on assessing how well participants tolerate the drug. Typically, some initial safety information is available by this stage, but it continues to be evaluated to ensure it does not cause serious side effects. Participants in the trial will have their health closely monitored to address any potential issues promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Thyroid Eye Disease?

Researchers are excited about TOUR006 for Thyroid Eye Disease because it offers a potentially new mechanism of action compared to current treatments like Tepezza, which targets the IGF-1 receptor. TOUR006 is a monoclonal antibody administered via subcutaneous injection, which could provide a convenient alternative to existing intravenous therapies. Additionally, with two different dosing options (20 mg and 50 mg), TOUR006 offers flexibility in tailoring treatment to patient needs, potentially enhancing its effectiveness and safety profile.

What evidence suggests that TOUR006 might be an effective treatment for Thyroid Eye Disease?

Research suggests that TOUR006 might help treat Thyroid Eye Disease (TED). Studies have found a link between high levels of interleukin-6 (IL-6) and TED. By targeting IL-6, TOUR006 could reduce inflammation and symptoms of TED. Although detailed human data on TOUR006 is still being gathered, its mechanism shows promise for managing TED, especially during active phases. Early results indicate that the treatment may reduce the eye bulging (proptosis) often seen in TED. Participants in this trial will receive either a 20 mg or 50 mg dose of TOUR006, or a placebo, to evaluate its effectiveness and safety. ^{1 3 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Tourmaline Bio

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• TOUR006

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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

Tourmaline Bio, Inc.

Lead Sponsor

Trials

2

Recruited

220+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06088979

NCT06088979 | A Study to Investigate Efficacy and Safety ... A Study to Investigate Efficacy and Safety of TOUR006 in Participants 18 to 80 Years of Age With Thyroid Eye Disease (spiriTED) · Study Overview · Contacts and ...

2. tourmalinebio.com tourmalinebio.com/spirited/

Clinical research study for patients with thyroid eye disease. The spiriTED study is evaluating the efficacy and safety of 2 different doses of TOUR006 compared with placebo in patients with moderate to severe active TED.

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-tour006-for-adults-with-thyroid-eye-disease/

Study on the Effects of TOUR006 for Adults with Thyroid ... The purpose of the study is to evaluate how effective and safe TOUR006 is in treating people with Thyroid Eye Disease. Participants in the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11175988/

A Review of Novel Medical Treatments for Thyroid Eye ... There has been no effective medication to prevent proptosis in thyroid eye disease until 2020 when the anti–insulin-like growth factor 1 receptor (anti–IGF-1R) ...

5. ir.tourmalinebio.com ir.tourmalinebio.com/static-files/1d259dce-b360-46c9-bc70-740d1afe5dd8

The role of IL-6 in thyroid eye disease Elevated serum interleukin-6 (IL-6) levels have been shown to correlate with disease activity in patients with thyroid eye disease (TED), ...

6. ir.tourmalinebio.com ir.tourmalinebio.com/news-releases/news-release-details/tourmaline-bio-announces-fda-clearance-investigational-new-drug

Release Details - Investor Relations - Tourmaline Bio, Inc. TOUR006 is a fully-human, anti-IL-6 antibody with differentiated properties including high binding affinity to IL-6 and a naturally long half-life.

7. withpower.com withpower.com/trial/phase-2-eye-diseases-9-2023-9764b

TOUR006 for Thyroid Eye Disease (spiriTED Trial) 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 ...