BRS201 for Sclerosing Cholangitis

(DOLPHIN Trial)

Overseen By Siani Ellis, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Ursodeoxycholic acid

Must not be taking: Vitamin C, Prednisone

Disqualifiers: Advanced liver disease, Cancer, others

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

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BRS201, to determine its effectiveness for people with primary sclerosing cholangitis, a condition that inflames and scars bile ducts. Participants will receive both the active drug and a placebo (a pill with no active drug) over an 8-week period to compare their effects. The study aims to assess how well BRS201 manages this condition. Ideal participants have had a confirmed diagnosis of primary sclerosing cholangitis for at least 6 months and experience symptoms that interfere with daily life. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop all current medications, but you cannot use vitamin C or prednisone during the study. If you are on ursodeoxycholic acid, you must be on a stable dose for over 6 months or have stopped it more than 4 weeks before screening.

Is there any evidence suggesting that BRS201 is likely to be safe for humans?

Research shows that BRS201, also known as hydroxocobalamin, has been studied for safety in other research. It is being tested as a treatment for ulcerative colitis, another inflammatory condition. Although specific safety data from these studies is not available, testing BRS201 for multiple conditions suggests it is considered potentially safe for humans.

BRS201 is used in this study because it is already an FDA-approved product for intravenous (IV) use, indicating its safety in that form. However, this trial will test the drug in pill form, which might yield different safety results.

This clinical trial is in phase 2, focusing on the treatment's tolerability and safety. This phase is crucial for identifying any side effects. Researchers will closely monitor participants for negative reactions, ensuring their safety remains a top priority. ^{1 2 3 4 5}

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

BRS201 is unique because it offers a novel approach to treating sclerosing cholangitis, a condition currently managed with options like ursodeoxycholic acid and endoscopic interventions. Unlike these standard treatments, BRS201 introduces a new delivery method with both oral and IV administration options, potentially enhancing its effectiveness. Researchers are particularly excited about its potential to provide quicker relief and better outcomes, as it combines a one-time IV dose with ongoing oral treatment, which might offer more robust and sustained results compared to existing therapies.

What evidence suggests that BRS201 might be an effective treatment for sclerosing cholangitis?

Research shows that BRS201, also known as hydroxocobalamin, might help people with primary sclerosing cholangitis (PSC). Hydroxocobalamin, a type of vitamin B12, may assist in cleaning the liver. Studies on similar conditions, such as ulcerative colitis, have shown it might reduce inflammation. Although researchers are still learning about BRS201's effectiveness for PSC, its mechanism suggests it could help manage symptoms. Early results from related conditions offer hope for its use in PSC. Participants in this trial will receive varying dosages of BRS201 or a placebo to evaluate its effectiveness and safety for PSC. ^{1 3 4 6 7}

Who Is on the Research Team?

Joshua A Korzenik, MD

Principal Investigator

Brigham and Womens Hospital

Are You a Good Fit for This Trial?

This trial is for people who've had primary sclerosing cholangitis (PSC) for at least 6 months, confirmed by specific imaging tests. They should have a certain liver enzyme level above normal and if taking ursodeoxycholic acid, the dose must be stable for over 6 months or stopped more than 4 weeks before screening.

Inclusion Criteria

I have been diagnosed with PSC for at least 6 months, confirmed by a specific bile duct scan.

ALP > 1.5 times the upper limit of normal (ULN) at screening.

I have been on a stable dose of ursodeoxycholic acid for over 6 months or stopped it more than 4 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants will take the study drug BRS201 for 4 weeks and a placebo drug for 4 weeks in a randomized order, involving oral medication and possibly an IV dose.

8 weeks

9 visits (remote), in-home visits for lab tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BRS201
• Placebo

Trial Overview The study tests BRS201's effectiveness in treating PSC. It's an 8-week cross-over trial where participants take BRS201 and a placebo in random order for four weeks each as oral medication, possibly with an IV dose. There are nine remote visits involving blood draws and stool samples.

How Is the Trial Designed?

Group I: BRS201 Arm Active Control 1 Intervention

In Group 1 of the study, subjects will take oral study drug at 1.2g twice daily, PO (2.4g daily) for 4 weeks. In Group 2 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) for 4 weeks. In Group 3 of the study, subjects will take receive a one-time 5g IV dose of the study drug using the FDA-approved IV product followed by the oral study drug at 2g twice daily, PO (4g daily) for 4 weeks. In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.

Group II: Placebo Arm Placebo Group 1 Intervention

In Group 1 of the study, subjects will take oral placebo at 1.2g twice daily, PO (2.4g daily) for 4 weeks. In Group 2 of the study, subjects will take oral placebo at 2g twice daily, PO (4g daily) for 4 weeks. In Group 3 of the study, subjects will take receive a one-time 5g IV dose of the study drug using the FDA-approved IV product followed by the oral placebo at 2g twice daily, PO (4g daily) for 4 weeks. In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

In a study of 335 patients who underwent liver transplantation for primary sclerosing cholangitis (PSC), biliary strictures (BS) occurred in 36.1% of patients after a mean of 3.9 years, and recurrent PSC (recPSC) was found in 20.3% after 4.6 years, both significantly impacting long-term survival rates.

Independent risk factors for developing BS and recPSC included donor age, inflammatory bowel disease (IBD), and INR levels at the time of transplantation, which can help categorize patients into risk groups for these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biliary strictures and recurrence after liver transplantation for primary sclerosing cholangitis: A retrospective multicenter analysis. Hildebrand, T., Pannicke, N., Dechene, A., et al.[2022]

In a study of 67 patients with IgG4 sclerosing cholangitis (IgG4-SC), the majority were male (76%) with a mean age of 63.3 years, and the most common symptoms were jaundice (62%) and abdominal pain (42%).

Treatment with prednisolone was effective, showing a partial or complete response in 95% of patients, although 42% experienced relapse after stopping the medication; importantly, progression to liver cancer was rare during a median follow-up of 3.9 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study. Kemp, W., Majeed, A., Mitchell, J., et al.[2022]

Primary sclerosing cholangitis (PSC) is a progressive liver disease with no effective treatments currently available, and it often leads to serious complications like cirrhosis and bile duct cancer over a long period, typically a decade or more.

Management of PSC focuses on symptom relief and addressing complications, with options like balloon dilatation for strictures and liver transplantation for advanced cases, while experimental therapies such as immunosuppressive and choleretic agents are being tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Fifth Carlos E. Rubio Memorial Lecture. Sclerosing cholangitis: pathogenesis, pathology, and practice. Larusso, NF.[2018]

Overlap syndrome between primary biliary cholangitis and primary sclerosing cholangitis is extremely rare, with only a few cases reported, highlighting the need for awareness and recognition of this condition in clinical practice.

In two cases of Tunisian female patients, both were successfully treated with ursodeoxycholic acid, demonstrating its potential efficacy in managing symptoms associated with this overlap syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overlap syndrome of primary biliary cholangitis and primary sclerosing cholangitis: two case reports. Yacoub, H., Ben Azouz, S., Hassine, H., et al.[2023]

In a study of 219 patients with primary sclerosing cholangitis, a higher dose of ursodeoxycholic acid did not show a statistically significant benefit on survival or prevention of liver transplantation compared to placebo over 5 years.

Despite some trends towards lower liver transplantation rates and decreased liver enzyme levels in the ursodeoxycholic acid group, there were no significant differences in symptoms or quality of life between the treatment and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Olsson, R., Boberg, KM., de Muckadell, OS., et al.[2022]

Sclerosing cholangitis is a rare and progressive liver disease primarily affecting the biliary tract, often associated with conditions like autoimmune hepatitis and inflammatory bowel disease, and is more common in males and Caucasians.

While ursodeoxycholic acid can improve biochemical markers, it does not extend survival without a transplant; orthotopic liver transplantation is currently the only effective long-term treatment, offering good survival rates for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sclerosing cholangitis: pediatric perspective. Kerkar, N., Miloh, T.[2021]

The BISCIT study aims to determine if scheduled biliary interventions every 8 weeks can reduce the incidence of cholangiosepsis, liver transplantation, or death in patients with secondary sclerosing cholangitis, involving 104 patients randomized across ten sites.

This study is significant as it seeks to establish a new evidence-based treatment approach for SSC-CIP, which could potentially improve patient outcomes and change the current standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BISCIT: Biliary interventions in critically ill patients with secondary sclerosing cholangitis-a study protocol for a multicenter, randomized, controlled parallel group trial. Stahl, K., Klein, F., Voigtländer, T., et al.[2023]

Ursodeoxycholic acid (UDCA) is the most promising treatment for primary sclerosing cholangitis, as it improves biliary secretion and may reduce the risk of colorectal and bile duct cancers, although its effects on liver histology and survival remain unclear.

Endoscopic treatment of dominant stenoses in patients with primary sclerosing cholangitis has been shown to improve cholestasis and extend survival, highlighting the importance of managing complications associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary sclerosing cholangitis. Rost, D., Kulaksiz, H., Stiehl, A.[2020]

In a study of 370 patients with primary sclerosing cholangitis, 13% were diagnosed with cholangiocarcinoma, highlighting the need for regular screening in this population to detect early tumors.

Patients who underwent surgical treatments, such as transplantation or hepatic resection, had significantly better survival outcomes (median survival of 7.6 months for transplantation and 52.8 months for resection) compared to those receiving palliative care (median survival of 2.6 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholangiocarcinoma complicating primary sclerosing cholangitis: a 24-year experience. Morris-Stiff, G., Bhati, C., Olliff, S., et al.[2008]

Citations

1. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/540655

Detoxification of the Liver In PSC (Dolphin) This study is a clinical trial being done to investigate the efficacy of drug BRS201 (hydroxocobalamin) as a treatment in patients with primary sclerosing ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/487135

Treatment of UC With Novel Therapeutics - Carebox Connect This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with active mild ulcerative colitis.

3. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05835505/

Trial | NCT05835505 This study is a clinical trial being done to investigate the efficacy of drug BRS201 (hydroxocobalamin) as a treatment in patients with primary sclerosing ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11877274/

Assessing brodalumab in the treatment of primary sclerosing ... This is a phase 2a, open-label, multicentre pilot study, testing the safety of brodalumab, a recombinant human monoclonal antibody that binds with high ...

5. policylab.us policylab.us/clinical-trials/l/conditions/primary-sclerosing-cholangitis

Primary Sclerosing Cholangitis Clinical Trials - Policy Lab This pilot clinical trial will evaluate the initial safety and feasibility of microbiota transplant therapy (MTT) inpatients with primary sclerosing cholangitis ...

6. bwh.trialstoday.org bwh.trialstoday.org/trial/NCT05835505

Detoxification of the Liver In PSC (Dolphin) This study is a clinical trial being done to investigate the efficacy of drug BRS201 (hydroxocobalamin) as a treatment in patients with primary sclerosing ...

7. withpower.com withpower.com/trial/brs201-for-ulcerative-colitis-d32c1

BRS201 for Ulcerative Colitis (SHARC Trial) This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with acute ulcerative colitis.