Setanaxib for Primary Biliary Cholangitis

(TRANSFORM Trial)

No longer recruiting at 141 trial locations

Overseen By Stefan Carlsson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genkyotex Suisse SA

Must be taking: Ursodeoxycholic acid

Disqualifiers: Hepatic decompensation, Cirrhosis, Liver transplant, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test setanaxib, a potential treatment for primary biliary cholangitis (PBC), a liver disease. Researchers seek to determine how setanaxib affects a liver enzyme called alkaline phosphatase (ALP) over 24 weeks. Participants will receive either setanaxib in two different doses or a placebo. Individuals with PBC who have tried ursodeoxycholic acid (UDCA) without success or who experienced adverse side effects may be suitable for this study. As a Phase 2 trial, this study focuses on evaluating setanaxib's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been on a stable dose of certain medications like ursodeoxycholic acid, obeticholic acid, fenofibrate, or bezafibrate for more than 3 months before screening. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that setanaxib is likely to be safe for humans?

Research has shown that setanaxib is generally safe for patients. In one study, participants taking setanaxib did not report any major safety problems. Another study found that setanaxib might even improve liver health, suggesting the treatment is safe for humans. However, the trial uses higher doses of setanaxib than earlier studies, so researchers continue to watch for any new side effects. Overall, the data so far show that setanaxib is well-tolerated, but monitoring responses to the higher doses in ongoing studies remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PBC?

Unlike the standard treatments for Primary Biliary Cholangitis (PBC), which typically involve ursodeoxycholic acid or obeticholic acid, Setanaxib is unique because it targets oxidative stress. Researchers are excited about Setanaxib because it works by inhibiting NOX enzymes, which are believed to play a role in the progression of PBC. This approach is different because it aims to reduce liver damage by tackling inflammation and fibrosis at its source. The potential for Setanaxib to offer a new mechanism of action brings hope for improved outcomes in PBC patients.

What evidence suggests that setanaxib might be an effective treatment for primary biliary cholangitis?

Research has shown that setanaxib may help reduce symptoms in people with primary biliary cholangitis (PBC). One study found that patients taking setanaxib experienced a 19% drop in alkaline phosphatase (ALP) levels with the 1600 mg dose. ALP is a marker for liver health, so lower levels indicate improvement. Patients also reported feeling less tired, a common issue with PBC. Setanaxib appears well-tolerated, with few side effects noted. These findings suggest that setanaxib could be a promising treatment for PBC. Participants in this trial will receive either a 1200 mg/day dose, a 1600 mg/day dose, or a placebo to further evaluate its effectiveness and safety. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults diagnosed with primary biliary cholangitis (PBC) who have an inadequate response or intolerance to ursodeoxycholic acid, and a liver stiffness of ≥8.8 kPa. Participants must not be pregnant, should use effective contraception, and cannot have certain conditions like high bilirubin levels, significant kidney dysfunction, other liver diseases, recent infections requiring antibiotics, or any history of hypersensitivity to setanaxib.

Inclusion Criteria

Serum ALP ≥1.67×ULN at Screening

Definite or probable PBC diagnosis as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:

For the purposes of this trial, women of childbearing potential are defined as 'Fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.'

Exclusion Criteria

My bilirubin levels are high, but my albumin levels are normal.

I have had a liver transplant, am waiting for one, or have severe liver disease.

Presence of any laboratory abnormality or condition that, in the opinion of the Investigator, could interfere with or compromise a participant's treatment, assessment, or compliance with the protocol and/or study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive setanaxib or placebo for a 24-week double-blind treatment period

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Setanaxib

Trial Overview The trial is testing the effectiveness of setanaxib on patients with PBC compared to a placebo. The main goal is to see if there's an improvement in liver function after 52 weeks for those taking setanaxib who previously didn't respond well or couldn't tolerate standard treatment.

How Is the Trial Designed?

Group I: Setanaxib 1600 mg/day Experimental Treatment 1 Intervention

Participants will be administered setanaxib at a dose of 1600 mg/day for the 24-week double-blind treatment period.

Group II: Setanaxib 1200 mg/day Experimental Treatment 1 Intervention

Participants will be administered setanaxib at a dose of 1200 mg/day for the 24-week double-blind treatment period.

Group III: Placebo Placebo Group 1 Intervention

Participants will be administered a placebo for the 24-week double-blind treatment period.

Who Is Running the Clinical Trial?

Genkyotex Suisse SA

Lead Sponsor

Trials

2

Recruited

130+

Calliditas Therapeutics Suisse SA

Lead Sponsor

Trials

2

Recruited

130+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9949832/

Impact of setanaxib on quality of life outcomes in primary ... At week 24, patients treated with setanaxib 400 mg BID reported greater mean (SE) absolute reductions from baseline in PBC-40 fatigue domain score [–3.6 (1.3)] ...

2. rarediseaseadvisor.com rarediseaseadvisor.com/news/trial-evaluating-setanaxib-pbc-met-primary-endpoint/

Trial Evaluating Setanaxib for PBC Meets Primary Endpoint Among the 76 participants enrolled in the study, those treated with setanaxib showed a 19% reduction in ALP in the 1600 mg arm and a 14% ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05014672

Study Details | NCT05014672 | A Trial of Setanaxib in ... The primary objective of this study is to evaluate the effect of setanaxib on alkaline phosphatase (ALP) at Week 24 in participants with PBC and with ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37183520/

Setanaxib, a first-in-class selective NADPH oxidase 1/4 ... This phase 2, randomized, multicentre study investigated the efficacy and safety of setanaxib in patients with PBC.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/liv.15596

Setanaxib, a first‐in‐class selective NADPH oxidase 1/4 ... Whilst the main aim of the study was not achieved, other results showed that setanaxib was well-tolerated by patients and may improve liver ...

6. prnewswire.com prnewswire.com/news-releases/calliditas-announces-positive-transform-phase-2b-topline-data-in-primary-biliary-cholangitis-302207350.html

Calliditas announces positive TRANSFORM Phase 2b ... Patients treated with setanaxib showed statistically significant improvements in the primary endpoint of ALP of 19% in the 1600mg arm and 14% in ...