CymaBay Therapeutics - RESPONSE Study

The RESPONSE clinical research study is a phase 3 clinical study (study number CB8025-32048) enrolling participants with primary biliary cholangitis (PBC) who have been taking UDCA (Ursodeoxycholic Acid also known as Ursodiol, URSO Forte, URSO 250, and Actigall) and don’t have adequate results or cannot tolerate UDCA. If you have PBC, you may qualify for this clinical research study.

A clinical research study, or clinical study, is a pre-planned set of tests conducted over time to learn about a potential new drug, treatment, or clinical method. In this study, researchers are trying to learn more about an investigational drug called seladelpar and whether seladelpar can improve PBC-related blood laboratory tests and whether it can improve symptoms of PBC, as well as the safety of seladelpar (the side effect profile) in people with PBC.

To qualify for the RESPONSE study you must:

• Be 18 to 75 years old (inclusive)
• Be diagnosed with PBC (Note, PBC was once called primary biliary cirrhosis. The current name, primary biliary cholangitis, is more medically accurate and less likely to cause misunderstanding.)
• Have been on a stable and recommended dose of UDCA (Ursodeoxycholic Acid also known as Ursodiol, URSO Forte, URSO 250, and Actigall) or you were required to stop taking the medication
• Have blood laboratory test results in the following range:
  • Alkaline phosphatase (ALP) at least 1.67 times the upper limit of normal (ULN)
  • Bilirubin test levels less than two times the ULN

For other requirements and more trial or PBC information, please go to clinicaltrials.gov.

After you volunteer for the study, the study doctor and staff will provide you with an informed consent document. If you consent to participate in the study, the study staff will give you some tests to make sure you qualify. This is called the “screening period,” and getting all of the results can take approximately 4 weeks.

If you are currently taking UDCA, you will continue to take approximately the same  recommended dose during study participation. At the screening visit your UDCA will be reimbursed, and if you qualify for the study, you will continue to receive UDCA reimbursement for 12 months.

You will also begin to take seladelpar or placebo orally (by mouth) once a day for 52 weeks. Seladelpar or placebo will be provided to you at no cost. You will not know whether you are receiving study drug or placebo. Participants already on URSO will continue that therapy for the duration of this study.

The RESPONSE study will also ask participants who enter the study to consider a biopsy at baseline and end of study treatment. The biopsy is voluntary and performed only if it is considered safe by the study doctor. Participating in this aspect of the research study is important to help researchers and regulators better understand the changes in your liver health and the effect that seladelpar has on your liver health.

There is a 2 in 3 chance that you will receive seladelpar and a 1 in 3 chance you will receive placebo in this study. Placebo is an inactive substance that looks like seladelpar. During the study, neither you nor your study doctor will know if you are receiving placebo or seladelpar.

You may be reimbursed for study-related travel expenses you incur.

The study will last for a total of about 60 weeks.

Yes, after participation in the RESPONSE study, you may be eligible to participate in the ASSURE long-term study where all participants receive Seladelpar and there is no placebo (CB8025-31731-RE).

You will receive seladelpar (study drug) and UDCA (Ursodeoxycholic Acid also known as Ursodiol, URSO Forte, URSO 250, and Actigall, if applicable) at no cost to you. At the screening visit your UDCA will be reimbursed, and if you qualify for the study, you will continue to receive UDCA reimbursement for 12 months.

By participating in the RESPONSE study, you will contribute to PBC research and you will be helping to develop possible future treatment options for people with PBC, including yourself.

There is no guarantee that being treated with seladelpar will have any effect on your itching caused by liver disease (also referred to as pruritus). In a previous clinical study, seladelpar did not appear to be associated with pruritus, and preliminary data suggests that seladelpar may help improve PBC-related itch.

The purpose of the RESPONSE study, which involves research, is to determine if seladelpar is safe and effective in treating patients with PBC compared to placebo (which looks like the study drug but is not active medication). Seladelpar is still an investigational drug that is not currently approved in any country or for any indication. Consequently, its safety profile has still not been fully determined. To date, 315 PBC patients have received seladelpar in clinical studies. In these studies, 106 received seladelpar treatment for ≥ 1 year, and 51 patients for ≥ 2 years. The most common adverse events are pruritus (itching), nausea (feeling sickness with the urge to vomit), urinary tract infection, diarrhea, and upper abdominal pain.

The RESPONSE study is only evaluating the effectiveness and safety of seladelpar in participants with primary biliary cholangitis (PBC).

In a clinical research study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or changes to participants’ behavior, such as diet. Clinical research studies may compare a new medical approach to a standard one that is already available, to a placebo that contains no active ingredients, or to no intervention. Some clinical research studies compare interventions that are already available to each other. When a new product or approach is being studied, it is not usually known whether it will be helpful, harmful, or no different than available alternatives (including no intervention). The investigators try to determine the safety and efficacy of the intervention by measuring certain outcomes in the participants. For example, investigators may give a drug or treatment to participants who have high blood pressure to see whether their blood pressure decreases. Clinical research studies used in drug development are sometimes described by phases, from 1 to 3, depending on the stage of development.

To make an informed decision about whether to participate or not in a clinical research study, people need to be informed about:

• What will be done to them
• How the protocol (plan of research) works
• What risks or discomforts they may experience
• Participation being a voluntary decision on their part

As new investigational medical products are being developed, no one knows for sure how well they will work, or what risks they will find. Clinical research studies are used to answer questions such as:

• Are new investigational medical products safe enough to outweigh the risks related to the underlying condition?
• How should the product be used? For example, what are the best dose, frequency, or any special precautions necessary to avoid problems?
• How effective is the investigational medication product at relieving symptoms, treating or curing a condition?

This information is provided to potential participants through the informed consent process. Informed consent means that the purpose of the research is explained to them, including what their role would be and how the study will work.

All this information is included in the informed consent document. Subjects participating in this study will have to sign this document before any study related procedure can be performed by the research staff.

For additional information and to view the RESPONSE study protocol, please visit clinicaltrials.gov (study number CB8025-32048).

The purpose of this study is to test seladelpar to see if it can improve the results of your PBC-related lab results and symptoms of PBC, such as itching. The goal of the study is to find new treatments to help PBC patients.