Batoclimab for Thyroid Eye Disease

Recruiting at 43 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

Trial Summary

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.

What evidence supports the effectiveness of the drug Batoclimab for treating Thyroid Eye Disease?

Research shows that Batoclimab, an FcRn inhibitor, can reduce harmful antibodies that contribute to Thyroid Eye Disease, suggesting its potential effectiveness in treating this condition. ^{1 2 3 4 5}

Is Batoclimab safe for humans?

Batoclimab, also known as an anti-FcRn monoclonal antibody, has been studied for its effects on the immune system, particularly in reducing certain antibodies. While specific safety data for Batoclimab in humans is not detailed in the provided research, similar therapies have been evaluated and shown to have predictable effects on antibody levels, suggesting a potential for safe use in humans. ^{1 3 4 6 7}

How is the drug Batoclimab unique for treating thyroid eye disease?

Batoclimab is unique because it works by inhibiting the neonatal fragment crystallizable receptor (FcRn), which reduces harmful antibodies that contribute to thyroid eye disease. This mechanism is different from other treatments like Teprotumumab, which targets a different receptor, or Rituximab, which depletes certain immune cells. ^{3 4 5 8 9}

What is the purpose of this trial?

This is a 2-cohort (observational and treatment cohort) extension study for participants completing feeder studies (IMVT-1401-3201 or IMVT-1401-3202). The observational cohort will assess the durability of proptosis response of feeder studies off treatment. The treatment cohort will evaluate the efficacy of batoclimab as assessed by proptosis responder rate.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Unidirectional transport of IgG by neonatal Fc receptor in human thyrocytes varies across different IgG subclasses. [2019]

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

The thyrotropin receptor in thyroid eye disease. [2005]

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

Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The expression and function of the neonatal Fc receptor in thyrocytes of Hashimoto's thyroiditis. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2020]

7. England 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. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Intraorbital injection of rituximab: a new approach for active thyroid-associated orbitopathy, a prospective case series. [2015]

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

Rituximab for thyroid eye disease. [2018]