A clinical study to evaluate the effects of RO7795068 in patients with obesity or overweight, with or without type 2 diabetes

1. Why is this study needed?

Obesity is a complex, long-term medical condition that can lead to various health problems, including issues with physical function and mental health. Many different factors contribute to obesity, such as genetics, biology, the environment a person lives in, and their socio-economic situation. Obesity or overweight and type 2 diabetes (T2D) are closely connected. T2D is a condition where blood sugar stays too high because the body does not respond properly to insulin, and over time, may not produce enough of it. Insulin is a hormone that helps control blood sugar levels by allowing sugar from food to be used for energy. Living with obesity or overweight can make T2D harder to manage, while losing weight can help improve T2D. There is still a need for treatment options that help people achieve a healthier weight and better blood sugar control.

This study is testing a medicine called RO7795068. It is being developed to treat obesity or overweight in people who live with or without T2D.

RO7795068 is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved RO7795068 for the treatment of obesity or overweight.

This study aims to compare the effects of RO7795068 against non-active medicine (placebo) in people with obesity or overweight, with or without T2D.

2. Who can take part in the study?

People (males and females) who are 18 years or older with obesity or overweight can take part in the study whether or not they have T2D. People without T2D can join the study if they have a body mass index (BMI) of 28 kg/m2 or higher. They can also join if their BMI is between 24 and 28 kg/m2 and they have at least one of the following: higher-than-normal blood sugar level (prediabetes), high blood pressure, high cholesterol, breathing problems during sleep, fatty liver or certain heart conditions. People with T2D can take part if their BMI is 24 kg/m2 or higher.

People may not be able to take part in this study if they have gained or lost more than 5 kg in the past 3 months. People whose weight is affected by certain medical conditions or genetic disorders, or who have received certain weight loss treatments in the last 6 months will also not be able to take part. People who are pregnant, planning to become pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place from 4 weeks before the start of treatment.

Everyone who joins this study will be split up into 4 groups randomly (like flipping a coin).

• Group 1 will receive placebo as a self-administered injection under the skin (subcutaneous) once a week for 52 weeks
• Group 2, 3, and 4 will receive low, medium and high doses of RO7795068 as a self-administered injection under the skin once a week for 52 weeks. All groups will start at the same low dose, which will gradually increase over time until each group reaches its target dose.

Participants will have an equal chance of being placed in any of the groups.

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’ (a medicine that contains no active ingredients but looks the same and is taken in the same way as the study medicine). Comparing results from the different groups helps researchers know if any changes seen result from the study medicine or occur by chance.

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 expected 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 every 4 weeks for the first 36 weeks, and then every 8 weeks after that. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have 1 follow-up visit after 4 weeks of completing the study treatment, during which the study doctor will check on the participant’s well being. Total time of participation in the study will be about 1 year and 2 months. 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 results measured in the study to assess if the medicine has worked are the percentage change in the body weight from the start of the study to week 52. Other key results measured in the study include:

• Number of participants who achieve various levels of weight loss (5%, 10%, 15%, 20%) by week 52
• Changes in body weight (in kilograms) and waist size by week 52
• Changes in blood sugar control, including fasting blood glucose, and insulin for all participants, and HbA1c (average blood sugar over the past 2–3 months) for those with T2D or prediabetes, by week 52
• Changes in measures related to the heart (cholesterol, triglycerides, and blood pressure), and ability to do daily activities by week 52
• Changes in body composition (such as the amount of fat and muscle), measured by an optional magnetic resonance imaging (MRI) scan for participants who agree to it, by week 52
• 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.

RO7795068 has had limited testing in humans. Therefore, the unwanted effects of this medicine are not known now. Participants will be told about the possible unwanted effects based on laboratory studies or knowledge of similar medicines. The possible unwanted effects include wanting to throw up, throwing up, inflammation of the gall bladder and pancreas, loose, watery [and more frequent] stools, and low blood sugar. Known unwanted effects of injection include a reaction around the site where the injection was given.

The study medicines may be harmful to an unborn baby. Women must take precautions to avoid exposing an unborn baby to the study treatment.