Batoclimab for Thyroid Eye Disease

Recruiting at 63 trial locations

Overseen By Central Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Immunovant Sciences GmbH

Disqualifiers: Surgery, Irradiation, Medical therapy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment called batoclimab (an anti-FcRn monoclonal antibody) for individuals with Thyroid Eye Disease (TED). It consists of two parts: one group of participants will be monitored to assess the stability of their eye condition without treatment, while the other group will receive batoclimab to determine if it alleviates symptoms, particularly eye bulging. This trial targets individuals who have completed a previous TED study and do not require immediate surgery or other treatments. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

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

Research has shown that batoclimab has been tested in several studies to assess its safety and effectiveness. In these studies, participants generally tolerated batoclimab well. Some studies used doses similar to those planned for this trial—680 mg and 340 mg administered as injections under the skin. Results suggest that most people handle the treatment without serious problems.

Some participants experienced minor side effects, usually mild, such as headaches and mild reactions at the injection site, like redness or swelling. Serious side effects were rare, indicating a positive safety profile.

Overall, while more research is ongoing, current data suggests that batoclimab is generally safe for humans. However, like any treatment, there is always a chance of side effects, so discussing any concerns with the study team is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for thyroid eye disease?

Unlike the standard treatments for Thyroid Eye Disease, which often include steroids or surgery, batoclimab is unique because it targets the root cause of the condition by modulating the immune system. Batoclimab is an anti-FcRn antibody, which works by reducing harmful autoantibodies that contribute to the symptoms of the disease. This targeted approach not only has the potential to be more effective but also minimizes the side effects commonly associated with steroids. Researchers are excited about batoclimab because it offers a promising new way to manage Thyroid Eye Disease with potentially fewer side effects and improved outcomes.

What evidence suggests that batoclimab might be an effective treatment for thyroid eye disease?

Research has shown that batoclimab, which participants in this trial may receive, might help treat Thyroid Eye Disease (TED). In one study, batoclimab, administered as an injection under the skin, reduced TED symptoms, with patients experiencing less eye bulging, known as proptosis. Batoclimab works by blocking a protein that can cause inflammation. Early trials suggest it could be a promising treatment for people with TED. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals who have completed a previous study on thyroid eye disease (TED) at week 24, don't need urgent surgery, and haven't stopped using batoclimab permanently. They should not be planning any corrective procedures or other medical treatments for TED during the study.

Inclusion Criteria

I don't need surgery or specific treatments for thyroid eye disease during the study.

You have not stopped taking batoclimab for good.

There are other requirements in the study plan that participants must meet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Proptosis non-responders in feeder studies will be administered batoclimab of 680 mg SC for 12 weeks followed by 340 mg SC for 12 weeks

24 weeks

Observational

Proptosis responders in feeder studies will enter in a non-treatment observational study to assess the durability of proptosis response

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Batoclimab

Trial Overview The trial has two parts: one where participants are observed to see how long their improvement in eye bulging lasts without treatment, and another where the effectiveness of batoclimab is tested by checking if it reduces eye bulging.

How Is the Trial Designed?

Group I: Treatment Cohort Experimental Treatment 1 Intervention

Proptosis non-responders in feeder studies will be administered batoclimab of 680 milligram (mg) subcutaneous (SC) for 12 weeks followed by 340 mg SC for 12 weeks

Group II: Observational cohort Experimental Treatment 1 Intervention

Proptosis responders in feeder studies will enter in a non-treatment observational study

Batoclimab is already approved in European Union, United States for the following indications:

Approved in European Union as Batoclimab for:

• Thyroid Eye Disease (TED)

Approved in United States as Batoclimab for:

• Thyroid Eye Disease (TED)

Who Is Running the Clinical Trial?

Immunovant Sciences GmbH

Lead Sponsor

Trials

12

Recruited

1,400+

Published Research Related to This Trial

Intraorbital administration of rituximab (RTX) significantly reduced disease activity in patients with thyroid-associated orbitopathy (TAO), with a notable improvement in clinical activity scores (CAS) for all five patients studied.

The treatment was well-tolerated, with no major side effects reported and only minor side effects in two patients, suggesting that RTX is a safe and promising option for patients unresponsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraorbital injection of rituximab: a new approach for active thyroid-associated orbitopathy, a prospective case series. Savino, G., Balia, L., Colucci, D., et al.[2015]

The study identifies the thyrotropin receptor (TSHR) as a potential autoantigen in thyroid eye disease (TED), with evidence of TSHR transcripts and proteins found in orbital adipose tissue of TED patients, suggesting its role in the disease's autoimmune response.

Animal studies indicate that a Th2-type immune response to TSHR may initiate TED, as shown by the development of orbital pathology in BALBc mice, while NOD mice did not exhibit similar symptoms, highlighting the complexity of the immune response involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The thyrotropin receptor in thyroid eye disease. Ludgate, M., Crisp, M., Lane, C., et al.[2005]

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]

Batoclimab, an FcRn inhibitor, significantly reduced pathogenic antibodies associated with thyroid eye disease (TED) in clinical trials, indicating its potential efficacy as a treatment.

While the randomized trial did not show a significant improvement in proptosis (eye bulging) at 12 weeks compared to placebo, earlier timepoints showed positive effects, and batoclimab was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease. Kahaly, GJ., Dolman, PJ., Wolf, J., et al.[2023]

A scaled-up pharmacokinetic model accurately predicted the effects of anti-FcRn monoclonal antibodies, like rozanolixizumab, on the levels of endogenous IgG in healthy human subjects, showing a maximum prediction error of only -8.50%.

The model suggests that anti-FcRn therapies may be more effective at lower doses in healthy individuals compared to patients with autoimmune diseases, indicating its potential for optimizing dosing strategies in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting the Effects of Anti-FcRn Therapy on the Disposition of Endogenous IgG in Humans. Li, T., Balthasar, JP.[2020]

Engineered human IgG1 antibodies with enhanced binding to the Fc receptor FcRn showed significantly longer half-lives in mice expressing human FcRn, indicating that modifying antibodies can improve their effectiveness in the bloodstream.

These modified antibodies not only persisted longer but also effectively reduced the half-life of other antibodies, suggesting potential for treating autoimmune diseases by promoting the clearance of harmful IgG antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Petkova, SB., Akilesh, S., Sproule, TJ., et al.[2022]

The neonatal Fc receptor (FcRn) in thyrocytes is down-regulated in Hashimoto's thyroiditis (HT), which affects the transport of IgG antibodies, particularly reducing IgG1 transport, potentially playing a protective role in HT pathogenesis.

FcRn mediates the transport of IgG from the basolateral to apical side in thyrocytes, with IgG1 being transported preferentially over IgG2 and IgG4, influenced by factors like IFN-γ and TNF-α, and regulated by T3 and TSH stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unidirectional transport of IgG by neonatal Fc receptor in human thyrocytes varies across different IgG subclasses. Zhao, C., Gao, Y., Yu, N., et al.[2019]

The study found that the neonatal Fc receptor (FcRn) is expressed in thyrocytes, but its levels are significantly lower in thyrocytes from patients with Hashimoto's thyroiditis (HT) compared to normal thyrocytes, suggesting a potential role in the disease's pathogenesis.

FcRn facilitates the internalization of IgG antibodies, including thyroglobulin antibodies (TgAb), in a pH-dependent manner, indicating that it may play a crucial role in the transport and metabolism of these antibodies within thyrocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The expression and function of the neonatal Fc receptor in thyrocytes of Hashimoto's thyroiditis. Zhao, C., Gao, Y., Zhao, L., et al.[2018]

In a study of 12 patients with thyroid eye disease (TED), rituximab treatment led to a significant decrease in Clinical Activity Scores (CAS) over a year, indicating improved symptoms associated with the disease.

The treatment was well tolerated with no adverse effects reported, and B-cell depletion was observed within a month, suggesting that rituximab may be a safe and effective option for managing TED, warranting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for thyroid eye disease. Silkiss, RZ., Reier, A., Coleman, M., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10655547/

Proof-of-concept and Randomized, Placebo-controlled Trials ... These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED. Keywords: ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05517421

NCT05517421 | Study to Assess Batoclimab in Participants ... To evaluate the efficacy of batoclimab 680 milligrams (mg) subcutaneous (SC) once a week (QW) for 12 weeks followed by 340 mg SC QW for 12 weeks versus ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10806862/

Batoclimab as induction and maintenance therapy in ... Batoclimab is a fully human anti-FcRn monoclonal antibody that is being developed as a low-volume subcutaneous (SC) injection for the treatment ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03938545

NCT03938545 | ASCEND GO-2: Study of RVT-1401 for the ... The purpose of the current study is to assess the efficacy and safety/tolerability of three dose regimens of RVT-1401 in the treatment of active, moderate to ...

5. clinicaltrials.eu clinicaltrials.eu/inn/batoclimab/

Batoclimab – Application in Therapy and Current Clinical ... This clinical trial is focused on studying Thyroid Eye Disease (TED), a condition that affects the eyes and is often associated with thyroid problems. The study ...