Clinical Research Directory

A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease

The main purpose of this study is to look at how efgartigimod affects thyroid function in adults with Graves' Disease (GD). The study will also check whether efgartigimod is safe and well tolerated. It will look at how efgartigimod is distributed and eliminated in the body, how it changes antibody levels, and how the immune system responds to it. The study consists of a part A double-blinded treatment period, a part B treatment/observation period and a part C open-label treatment/observation period. During the part A and part B treatment periods, participants will receive efgartigimod PH20 SC via Prefilled Syringe (PFS) or placebo. During the part C open-label treatment period, participants will receive efgartigimod PH20 SC PFS. Participation in the different parts of the study will depend on the participant's response to treatment. The total study duration for participants ranges from 63 to 135 weeks, depending on the response to treatment. More information can be found here: https://clinicaltrials.argenx.com/vitalithy

A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease

This is a multi-center, global, randomized, double-blind, placebo-controlled Phase 2b study to assess the efficacy, safety, and tolerability of IMVT-1402 in adult participants with Graves' disease (GD) who are hyperthyroid despite antithyroid drug (ATD) treatment.

Evaluation of YB-101 for Safety, Tolerability, Pharmacokinetics, and Efficacy in Graves' Disease

This study is being conducted to look at the effect YB-101 has on thyroid function. This study will also evaluate how safe and well tolerated YB-101 is and how it is distributed through the body. The study consists of a part 1, blinded treatment period, and a part 2 double-blinded treatment period. Participants will receive YB-101 or Placebo subcutaneously. Participants who participate in Part 1 can not participate in Part 2. Participants will complete 34-39 in-clinic visits in Part 1 or Part 2 over an approximate 40 week period.

A Study to Investigate the Efficacy and Safety of Rilzabrutinib in Adult Participants With Graves' Disease

This is a parallel group, Phase 2, 2-arm study to measure the treatment effect and safety of rilzabrutinib dose 1 or rilzabrutinib dose 2 in participants with Graves' disease, with and without Graves' orbitopathy, aged 18 years or older. Study details include: * Screening period (up to 4 weeks). * Treatment period (up to 16 weeks). * Follow-up period (4 weeks). The number of visits will be up to 13.

An Open-Label Study to Determine if BHV-1300 is Safe in Adults With Graves' Disease

To study the long-term safety and tolerability of BHV-1300

A Study to Learn About The Effects of Felzartamab on Thyroid Function and Its Safety in Adults With Graves' Disease Ages 18 to 75 Years Old

In this study, researchers will learn more about the use of felzartamab in participants with Graves' Disease, also known as GD. GD is an autoimmune disease, which means the body's immune system attacks its own healthy cells. In people with GD, the immune system produces abnormal antibodies, called thyroid-stimulating hormone receptor antibodies (TRAb), that attack the thyroid gland. This causes the thyroid to become too active and produce too much hormone, a condition called hyperthyroidism. Participants with GD are often treated with anti-thyroid drugs, or ATDs, which are medicines that help bring thyroid hormone levels back to normal. Felzartamab is designed to target certain immune cells that produce the abnormal TRAb antibodies. The main goal of the study is to learn whether felzartamab can help bring thyroid hormone levels back to normal and allow participants to stop taking ATDs. Participants will receive either felzartamab or placebo during the study. A placebo looks like the study drug but contains no real medicine. The main question that researchers want to answer is: • How many participants have normal thyroid levels without receiving any ATD medicine at Week 24? Researchers will also learn more about the safety of felzartamab and how the body processes the drug. The study will be done as follows: * Participants will be screened to check if they can join the study. * This is a double-blind study, which means neither the participants, study doctor, or site staff will know if participants are receiving felzartamab or a placebo. * Participants will be placed into 1 of 3 groups. Two groups will receive felzartamab while the other receives placebo. * Participants will receive felzartamab or placebo as intravenous (IV) infusions, which are slow injections into a vein using a needle. The Treatment Period will last 20 weeks. * During the Treatment Period, the study doctor may gradually lower the dose of the ATD if a participant's thyroid levels become normal. * Afterwards, participants will enter a follow-up period which will last 12 weeks. * In total, participants will have 22 study visits. Participants will stay in the study for about 9 months (up to 36 weeks).

Early Risk Stratification of Thyroid Eye Disease in Newly Diagnosed Graves' Disease

The aim of this observational study is to investigate why some people with newly diagnosed Graves' disease (GD) develop thyroid eye disease (TED), also known as Graves' orbitopathy, while others do not. The main questions the study aims to answer are: 1. What proportion of participants develop TED within one year of being diagnosed with GD? 2. Which early clinical signs, ophthalmological findings, blood biomarkers, tear-fluid biomarkers, or ocular surface microbiome characteristics are associated with an increased risk of developing thyroid eye disease? Participants with newly diagnosed GD will attend two study visits, one at baseline and one approximately one year later. At each visit, participants will: * Answer questions about their symptoms and quality of life * Undergo a standardized eye examination and have clinical photographs taken of their eyes * Provide blood samples, tear-fluid samples, and a small swab sample from the ocular surface The study will also include healthy volunteers and participants with moderate-to-severe TED. Participants in these comparison groups will attend one study visit. Researchers will compare findings across the groups to better understand the early clinical and biological changes associated with thyroid eye disease. The long-term aim is to improve the early detection and follow-up of people with GD who may be at increased risk of developing TED.

Evaluation of ETHY-001 for Safety, Tolerability, and Clinical Activity in Thyroid Eye Disease

The primary objective of study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ETHY-001 in healthy volunteers and participants with Thyroid Eye Disease after single subcutaneous doses.

Impact of Vitamin D Therapy on Thyroid Function and Antibody Levels in Pediatric Graves' Disease

The goal of this randomized pilot feasibility clinical trial is to determine the feasibility of implementing a protocol for a larger trial to assess the effects of high-dose vitamin D supplementation in pediatric patients (9-17 years old) newly diagnosed with Graves' disease. The main questions it aims to answer are: What are the recruitment and adherence rates for a larger trial using this protocol? Is the data collection process complete and robust enough for a larger trial? What are the potential barriers to implementing a larger-scale trial? Researchers will compare vitamin D supplementation plus standard methimazole therapy to methimazole therapy alone (with participants permitted to take up to 1000 International Units of vitamin D2 daily) to explore potential effects on thyroid hormone and antibody levels. Participants will: Be randomized to either the intervention or control group. Take study medications (vitamin D or placebo) as directed. Attend regular study visits for blood tests and clinical assessments. Complete medication logs.

Prophylactic Treatment of Graves Ophthalmopathy (GO) in Newly Diagnosed Graves' Disease (GD) With Atorvastatin (ATORGO)

Graves' disease is an autoimmune condition that causes an overactive thyroid. Some people with Graves' disease develop thyroid eye disease, also called Graves' orbitopathy, which can cause swelling around the eyes, eye discomfort, double vision, changes in appearance, and, in severe cases, problems with vision. The purpose of this study is to find out whether atorvastatin, a commonly used cholesterol-lowering medicine, can reduce the risk of developing active thyroid eye disease in adults who have recently been diagnosed with Graves' disease. A total of 554 participants will be randomly assigned to one of two groups. One group will receive atorvastatin 40 mg once daily for 12 months in addition to standard treatment for Graves' disease. The other group will receive standard treatment for Graves' disease alone. Participants will be followed for 18 months. During the study, participants will have regular assessments of their thyroid disease and their eyes. Blood samples and questionnaires about symptoms and quality of life will also be collected. The researchers will compare the two groups to determine whether atorvastatin reduces the development of active thyroid eye disease.

Microbiota and Immune SignatureS of Graves' Disease and Orbitopathy

Graves' disease (GD) is the commonest cause of hyperthyroidism, characterised by anti-thyrotropin receptor autoantibodies (TRAb) persistently stimulating the thyroid gland. Around 30-50% GD patients also develop Graves' orbitopathy (GO), an orbital inflammation causing disfigurement and visual problems; moderate-to-severe forms represent 5% of GO cases and are associated with high risk of sight loss. Some risk factors for GO have been identified (i.e. smoking, stress, high TRAb titres, severe hyperthyroidism) and predictive models for disease development and response to treatment have been attempted, but are still missing/incomplete. The GD/GO pathogenesis is multifactorial and not fully understood, including a complex interplay between genetic predisposition and environmental factors. A loss of immune tolerance has been observed; in particular an imbalance between T Helper 17 (Th17) and T Regulatory (Treg). The gut microbiota modulates the differentiation of immature T cells in the gut-associated-lymphoid-tissue and microbiota alterations seem involved in autoimmune diseases, including GD/GO. Indeed, a dysbiosis of the gut microbiota may alter the Treg/T17 balance and thus impact on immune homeostasis. The international EU-FP7 funded study "Investigation of Novel biomarkers and Definition of the role of the microbiome In Graves' Orbitopathy" (INDIGO) represented one of the first investigations about the role of gut microbiota in GD and GO diseases (https://cordis.europa.eu/project/id/612116), spanning across eight centres of four European countries: United Kingdom (Cardiff, Merthyr Tydfil, Newcastle upon Tyne and Moorfields), Italy (Milan and Pisa), Belgium (Brussels) and Germany (Essen). The INDIGO consortium provided the human gut microbiome analysis by 16S rRNA sequencing, performed on faecal samples of 105 patients (59 GD, 46 GO) and 41 controls enrolled between October 2014 and June 2016. It was discovered an increase of Actinobacteria phylum in both GD and GO compared with controls, and a selective enrichment of Roseburia spp. in moderate-severe GO compared with both GD and controls. The first objective of this MISS.GO study is to validate with advanced metagenomics techniques (Shotgun sequencing) the INDIGO study's gut microbiome findings, whose samples were stored in a biobank of UO1 (UNIMI). The Shotgun sequencing allows a deeper taxonomic investigation down to species level, while 16s rRNA sequencing is limited to genus level. Furthermore it increases the chances to detect low abundant species, not possible with 16S rRNA sequencing, and extends the microbiome analysis to yeasts, fungi and a variety of other microorganisms in addition to Bacteria and Archea, to which 16s rRNA sequencing is restricted. Furthermore, this study integrates the metabolomics analysis performed on stored plasma of INDIGO's patients. The MISS.GO study also includes a prospective phase were 59 subjects (33 GO, 9 GD and 17 controls) were recruited in the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Italy, to deliver an in depth analysis of the relationship between microbiota and immune system, since: 1. Advanced Shotgun sequencing is also applied to nasal swabs, in addition to faecal samples. The role of nasal microbiota, and its relationship with gut microbiota, will be explored for the first time in GD and GO patients; 2. Metagenomics data are integrated with metabolomics and proteomics analysis performed on plasma, faecal and nasal samples; 3. Such advanced microbiota's analyses are also integrated with paired immunophenotyping of lymphocytes resident within the organs targeted by autoimmunity in GD and GO patients (thyroid and lymph node) accessed by fine-needle aspiration (FNA), to study the bidirectional modulation between microbiota and immune system. The final goal of MISS.GO study, thanks to such integrated analysis of fecal and nasal metagenomics, metabolomics and metaproteomics, together with paired tissue-resident immunophenotyping, is to improve the current knowledge of GD and GO pathogenesis, aiming to identify prognostic GD and GO markers, predictive factors for GO development, and key microbiota and immune signatures that can be exploited for prevention, mitigation and therapeutic strategies.

Thyroid-Stimulating Hormone Receptor (TSHR) Blockade With REGN24493 in Adult Participants With Graves' Disease (GD)

This study will test an experimental Regeneron drug called REGN24493 hereby referred to as "study drug" to see if it can help treat Graves' disease. Graves' disease is a condition where the immune system causes the thyroid gland to make too much thyroid hormone. The main purpose of this study is to learn about the safety of REGN24493 and what side effects it might cause. The study is looking at: * What side effects REGN24493 might cause * How much REGN24493 is in the blood at different times * How REGN24493 affects thyroid hormone levels * If the body reacts to REGN24493 in a way that could affect participant's health * What is the best dose of REGN24493 for treating Graves' disease

A Long-Term Extension Study of IMVT-1402 in Adult Participants With Graves' Disease (GD)

This is a long-term extension study that will rollover participants completing feeder studies IMVT-1402-2502 (NCT06727604) or IMVT-1402-2503 (NCT07018323) to evaluate the efficacy and safety of IMVT-1402 in adult participants with GD. Eligible participants will be assigned to 1 of 3 study groups (Groups A, B and C) based on their GD status at the completion of their respective feeder study.

A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease

This is a study to assess the efficacy, safety, and tolerability of IMVT-1402 in adult participants with Graves' disease (GD) who are hyperthyroid despite antithyroid drug (ATD) treatment. The primary objective of this study is to evaluate the efficacy of IMVT-1402 versus placebo as assessed by T3 (total triiodothyronine \[T3\] or free triiodothyronine \[FT3\]), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and ATD dose at Week 26.

In Vivo CAR-T for Refractory Graves' Disease

Graves' disease is an autoimmune thyroid disorder characterized by the production of autoantibodies against the thyroid-stimulating hormone receptor (TRAb), leading to excessive thyroid hormone secretion and systemic manifestations. A subset of patients develop refractory disease, failing to achieve durable remission despite prolonged antithyroid therapy. This study aims to evaluate the safety and efficacy of HN2301, an in vivo CAR-T therapy in which host T lymphocytes are engineered and transformed to functional CAR-T cells via CD8 antibody-coated LNP delivery of CD19 CAR-mRNA. Participants with refractory Graves' disease will receive three to five administrations of HN2301 and will be regularly monitored for changes in thyroid function, TRAb levels, clinical response, and treatment-related adverse events. The study will provide preliminary evidence on whether HN2301 can induce sustained remission of refractory Graves' disease.

Allogeneic Anti-CD19/BCMA CAR-T for Refractory Graves' Disease

Graves' disease is an autoimmune thyroid disorder in which autoantibodies against the thyroid-stimulating hormone receptor (TRAb) lead to excessive thyroid hormone production and systemic complications, as well as thyroid eye disease and pretibial myxedema in some cases. Patients with refractory Graves' disease often fail to achieve durable remission despite prolonged antithyroid medication. This study aims to evaluate the safety and efficacy of RD06-05, an allogeneic dual CD19/BCMA CAR-T therapy, in participants with refractory Graves' disease, and will provide preliminary evidence on whether dual-targeting CAR-T therapy can induce sustained remission of refractory Graves' disease.

Assessment of Thyroid Doppler Ultrasound in Followup of Pediatric Graves' Disease

All cases of the study will be diagnosed as Graves' by History, examination, laboratory (FT3, FT4, TSH \& TRAbs), X-ray on left wrist for bone age, neck grey scale ultrasonography for thyroid gland size, shape, echotexture, vascularity and nodule characters if present with TIRAD score calculation. Then Color flow doppler ultrasound will be done to asses thyroid volume, number of vessels per square cm and inferior thyroid artery peak systolic velocity, end diastolic velocity and resistive index. Patients then will receive carbimazole antithyroid drug at dose 0.25-0.5 mg/kg/day PO \& the dose will be titrated according to thyroid function test after 4-6 weeks. Beta-adrenergic blockade will be added to all symptomatic cases. Regular follow up will be done every month of first 3 months of diagnosis and then every 3 months for 2 years by clinical and thyroid function test to asses response, compliance, complications, drug side effects, remission and relapses. Doppler ultrasound will be done at 0, 12 and 24 months.

Graves' Disease Remission Study: MycoMeth Combo

A randomized study to evaluate the efficacy and safety of combining mycophenolate mofetil with methimazole in patients with newly diagnosed Graves' disease.