A clinical trial to compare satralizumab against placebo in people with thyroid eye disease

1. Why is the GP44467 clinical trial needed?

This clinical trial aims to compare the effects, good or bad, of satralizumab versus placebo in people living with thyroid eye disease (TED, also known as Graves’ eye disease or Graves’ orbitopathy). A placebo looks like a drug but has no active ingredient. TED is an autoimmune disease in which the immune system mistakenly attacks healthy tissue around the eyes. Symptoms can be mild to severe including pain, bulging of the eyes and double vision. TED has an ‘active’ phase when eye muscles, eyes and eyelids become swollen, eyes become red and bulge, and fatty tissue behind the eyes gets larger. This is followed by an ‘inactive chronic’ phase when symptoms no longer get worse, but the fatty tissue hardens, and eye muscles are left scarred. Current treatment for moderate-to-severe active TED includes steroids, and/or teprotumumab (in the United States only), but these treatments do not work for everyone and can cause many side effects; whereas surgery is the only current treatment option for inactive chronic TED. New treatments are needed for TED. Satralizumab works by blocking the activity of a part of the immune system called interleukin-6, or IL-6 for short. Satralizumab is approved for the treatment of an autoimmune disorder that affects the spinal cord and nerves of the eyes (optic nerves) called neuromyelitis optica spectrum disorder (NMOSD); it is not currently approved for treating TED.

2. How does the GP44467 clinical trial work?

This clinical trial is for people living with moderate-to-severe TED. This clinical trial is split into two parts, each 6 months long. People who take part in this clinical trial (participants) will be given satralizumab OR placebo. The clinical trial doctor will see them at least every 4 weeks. These hospital visits will include checks to see how the person responds to the trial treatment and any side effects they may have. Participants will be contacted by telephone every 2 months for 6 months after the last dose to check for any side effects and changes to their health. The total time of participation in the clinical trial will be about 1 and a half years. Anyone who takes part in the trial is free to stop at any time.

3. What are the main endpoints of the GP44467 clinical trial?

The main clinical trial endpoint (the main result measured to see if the drug has worked) is the number of participants with active TED and a reduction of at least 2mm in eye-bulging after the first part of the trial.
Other factors that will be monitored for everyone in the trial (those with active or inactive TED) will be measured both at the end of the first and second part of the trial unless indicated. These include:

• Change in eye-bulging from the start of the trial
• The number of participants with:
  • a reduction of at least 2mm in eye-bulging
  • improved double vision (in participants with double vision at the start of the trial only)
  • no eye pain with or without moving their eyes at the end of the first part of the trial (in participants with active TED and eye pain at the start of the trial only)
  • an improvement in how their eyes work and look
  • a certain level of reduction in redness or swelling (inflammation) and a 2mm reduction in eye-bulging – known as the ‘overall response’
  • a certain level of reduction in redness or swelling
  • no or little redness or swelling (inflammation) at the end of the first part of the trial
  • an improvement in the dryness of their eyes (and other symptoms) at the end of the first part of the trial
  • a reduction in eye-bulging at the end of the first part of the trial, which worsens (by at least 2mm) by the end of the second part of the trial
  • a need for surgery for TED during the trial
• Change in redness or inflammation from the start of the trial (in participants with a reduction in eye-bulging after the first part of the trial only)
• Change in the amount of damage to the outer layer of the eye at the end of the first part of the trial
  
• The number and seriousness of side effects, and how the body processes satralizumab

4. Who can take part in this clinical trial?

People can take part in this trial if they are at least 18 years old, have no/controlled or mild thyroid problems, have active TED that began less than 1 year before the trial, or have had TED for between 1–10 years and chronic inactive TED for at least 6 months. People may not be able to take part in this trial if they have received certain treatments, including an IL-6-targeted medicine, or have certain medical conditions such as another eye disease, infections, history of cancer or drug allergies, or are pregnant or breastfeeding.

5. What treatment will participants be given in this clinical trial?

This is a ‘placebo-controlled’ clinical trial, which means that one of the groups will be given a substance with no active ingredients (also known as a ‘placebo’); it looks like the drug being tested but does not contain any real medicine. Comparing results from the different groups helps the researchers know whether any changes seen result from the drug or occur by chance. This is a double-masked trial, which means that neither the participant nor the clinical trial doctor can choose or know the group the participant is in, until the trial is over. This helps to prevent bias and expectations about what will happen. However, the participant’s clinical trial doctor can find out which group the participant is in, if their safety is at risk.

In the first part of the trial, everyone will be split into two groups randomly (like flipping a coin) and given either satralizumab OR placebo.

Participants will then be placed into a group depending on their TED symptoms after the first part of the trial. The clinical trial doctor and the participant will remain ‘masked’, which means they will not know which treatment was already given and which they will be given next. In the second part of the trial:

• Everyone who has an improvement in their symptoms will be split into 2 groups randomly and given either satralizumab or placebo, with an equal chance of being placed in either group
• Everyone who does not have an improvement in their symptoms will be given satralizumab

In both parts of the trial, satralizumab or placebo will be given as an injection under the skin every 2 weeks for the first 3 doses, then every 4 weeks for 5 months (7 doses in total).

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial). Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drug used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly. Participants will be told about the known side effects of satralizumab, and possible side effects based on human and laboratory studies or knowledge of similar drugs. Satralizumab and placebo will be given as injections under the skin (subcutaneous injections). Participants will be told about any known side effects of subcutaneous injections.

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.