A study to test the effectiveness and safety of RO7790121 for induction and maintenance therapy in patients with moderately to severely active Crohn's disease

1. Why is this study needed? 

Crohn's disease (CD) is a type of inflammatory bowel disease. It causes swelling of the tissues (inflammation) in the digestive tract. When people with CD have symptoms, their CD is said to be ‘active’. People with ‘moderately to severely active’ CD can have symptoms such as feeling tired or weak, belly pain, frequent loose or watery stools (diarrhoea), weight loss, and fever. 

Standard treatments for CD include medicines that reduce inflammation, such as corticosteroids, biologics and small molecules. But for many people living with CD, symptoms do not improve even with these treatments. Treatment can also stop working after a time or cause unacceptable unwanted effects that affect a person’s ability to continue on a therapy and function. So, better treatments are needed. 

This study is testing a medicine called RO7790121 (previously known as ‘PF-06480605’ or ‘RVT-3101’). RO7790121 is an investigational medicine being developed to treat CD. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not yet approved RO7790121 for treating CD. 

This study aims to compare RO7790121 as a long-term treatment with a ‘placebo’. A placebo is a medicine that contains no active ingredients but looks the same as the study medicine. Researchers want to see if RO7790121 works, how well it works and how safe it is when given over a long period of time. This is compared to a placebo in people living with moderately to severely active CD. 

2. Who can take part in the study? 

People aged 18 to 80 years old, and 16 to 17 years old in some countries, with moderately to severely active CD can take part in the study. Their CD diagnosis must have been confirmed by an ‘endoscopy’. An endoscopy is a procedure where a doctor uses a flexible tube with a camera on it to look inside the large intestine (colon). To take part, people also must have taken at least 1 other medicine for CD that didn’t work very well, stopped working or caused unacceptable unwanted effects. People cannot take part in this study if they have had 3 or more surgeries to remove part of the intestines, or they are taking certain medicines for CD. People who have certain other medical conditions such as ulcerative colitis, abnormal cells in their bowel (known as ‘dysplasia’), some types of cancer within the last 5 years, or certain infections such as HIV, hepatitis B or hepatitis C, also cannot take part. People who are pregnant, planning to get pregnant or to donate eggs or sperm, or are currently breastfeeding cannot take part in the study.

3. How does this study work? 

This study consists of a screening period, a treatment period of 1 year, an optional treatment extension period and a safety follow up period of 12 weeks. Participants will be screened to check if they are able to participate in the study. The screening period will take place from 1 to 35 days before the start of treatment.

This is a ‘placebo-controlled’ study. This means that participants are put in a group that will receive a medicine or a group that will receive ‘placebo’. Comparing results from the different groups helps researchers know if any changes seen result from the study medicine or occur by chance. 

Everyone who joins this study will be placed into 1 of 3 groups randomly. Participants will be given either RO7790121 (high or low dose injections) or placebo for up to 1 year. Study treatment will be given as a drip into the vein (known as an ‘infusion’) 4 times during the first 3 months, then as monthly injections under the skin for up to 1 year of treatment. Participants will have a 2 in 3 chance of being placed in an RO7790121 group and a 1 in 3 chance of being placed in the placebo group. All participants will continue to take their usual anti-inflammatory treatment for CD as well as the study treatment.

This is a double-blinded study. This means that neither the participants in the study nor the team running it will know which treatment is being given until the study is over. This is done to make sure that the results of the treatment are not affected by what people expect from the received treatment. However, the study doctor can find out which group the participant is in, if the participants' safety is at risk.

During this study, the study doctor will see participants regularly. The study doctor will see how well the treatment is working and any unwanted effects participants may have. If participants have been given at least 3 months of study treatment and the study doctor thinks it's suitable, they can agree to keep receiving treatment in an open-label extension of the study. Open-label means everyone involved, including the participant and the study doctor, will know the participant has been given RO7790121. Everyone who joins the extension will be given high-dose RO7790121 as monthly injections under the skin. Some visits may take place in the participant’s home by a nurse if they prefer. If CD gets worse during the extension, RO7790121 may be given every 2 weeks. Treatment will continue until RO7790121 is commercially available in that region or until the Sponsor decides to end the study, whichever is earlier. Participants will have 2 follow-up visits 6 weeks and 3 months after completing the study treatment, during which the study doctor will check on the participant’s wellbeing. Total time of participation in the study could be up to 1 year and 4 months, not including the open-label extension. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main result measured in the study to assess if the medicine has worked is the number of participants with no or very few signs of CD or improved intestine health (such as fewer and smaller ulcers) after 1 year of treatment.

Other key results measured in the study include:

• The number of participants with no or improved signs or symptoms of CD after 3 months of treatment, compared to the start of the study. This includes: the average number of bowel movements per day and the average daily belly pain score. It also includes improvements in the health of their intestines.
• The number of participants who have no visible bowel inflammation after 3 months and at 1 year.
• The number of participants who have no or few symptoms of CD at 1 year and who have not taken steroids during the last 2 months.
• The number of participants with a passageway, called a ‘fistula’, between the intestines and the exterior of the body, at 3 months and 1 year after treatment.
• How much participants report that their CD symptoms have changed and how severe symptoms are.
• The number and seriousness of unwanted effects.

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future. It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study drug
Participants may have unwanted effects of the drug used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects. RO7790121 has had limited testing in humans. Participants will be told about the known unwanted effects of RO7790121 and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include allergic reactions, feeling sick and joint pain. Known unwanted effects of infusions include throwing up, wanting to throw up, a feeling of coldness that makes the body shiver, low or high blood pressure, fever, pain or discomfort in the head. Known unwanted effects of infusions and injections include a reaction on the skin where it has been pricked with a needle to give a treatment. The study medicine(s) may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.