Osivelotor for Liver Disease

No longer recruiting at 3 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Disqualifiers: Hepatic carcinoma, Hepatorenal syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Osivelotor to understand its processing in individuals with liver disease. Researchers aim to determine if Osivelotor is safe and how it moves through the bodies of those with mild or moderate liver issues. Participants will take a single dose of the medicine and undergo various tests, including blood samples and physical exams, to collect this information. Individuals with stable liver function loss who haven't had surgeries affecting digestion might be suitable candidates. The trial lasts up to 112 days and requires a short stay at the clinic. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should have stable concomitant medications for managing their medical history, which suggests you may continue your current medications if they are stable.

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

Research shows that osivelotor may help treat certain conditions by improving red blood cell health and blood flow. However, specific safety information about osivelotor, particularly for individuals with liver disease, remains unavailable. This study is in its early stages and primarily focuses on understanding how the treatment works in the body rather than on safety results.

As an early-phase study, detailed safety information in humans might not yet be fully available. This phase typically marks the first step in testing new treatments in people. It helps researchers learn about the treatment's safety and how the body processes it. While information is still limited, the treatment is being carefully studied to ensure its safety for future use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care options for liver disease, which often involve lifestyle changes, medications to manage symptoms, or liver transplants, osivelotor offers a novel approach. Osivelotor is unique because it targets liver conditions directly through a new active ingredient, focusing specifically on patients with hepatic impairment. This treatment is administered orally, which might offer a more convenient and non-invasive option compared to other interventions. Researchers are excited about osivelotor because it has the potential to effectively manage liver disease with a single dose, possibly paving the way for a more streamlined and patient-friendly treatment regimen.

What evidence suggests that Osivelotor might be an effective treatment for liver disease?

Research has shown that Osivelotor helps red blood cells carry oxygen more effectively. Initially, researchers studied it for treating sickle cell disease (SCD). Early results in SCD patients showed that Osivelotor improved the health of red blood cells and blood flow, suggesting it might enhance oxygen delivery. In this trial, participants with mild or moderate hepatic impairment will receive a single dose of Osivelotor to evaluate its potential benefits for liver disease. Although it has not yet been proven effective for liver disease, its mechanism offers hope for addressing similar issues related to oxygen transport in the body. ^{1 3 4 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This study is for individuals with stable liver disease of mild or moderate severity, who have a BMI between 16 to 40 kg/m2 and weigh over 50 kg. They should not have had significant changes in their condition within the last month and must be on stable medications for any other health issues.

Inclusion Criteria

My current medications for other conditions are stable.

Body mass index (BMI) of 16 to 40 kg/m2, inclusive; and a total body weight greater than 50 kg (greater than 110 lb)

My liver function is stable, fitting into Class A or B.

Exclusion Criteria

I have had surgery that could affect how my body absorbs medication.

I have liver problems confirmed by tests or a doctor's exam.

I have liver cancer, kidney issues related to liver disease, or a short expected lifespan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Osivelotor orally under fasted conditions, followed by blood sampling and physical examinations

5 days

5 days onsite

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

5 study visits at the clinic

What Are the Treatments Tested in This Trial?

Interventions

• Osivelotor

Trial Overview The trial is testing how Osivelotor, a medication taken by mouth, is processed by people with impaired liver function. Participants will take one dose before breakfast on the first day and undergo blood tests, physical exams, and other assessments over a maximum of 112 days with five clinic visits.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 1 Intervention

Participants with mild hepatic impairment will receive a single dose of osivelotor, administered orally under fasted conditions.

Group II: Group 1 Experimental Treatment 1 Intervention

Participants with moderate hepatic impairment will receive a single dose of osivelotor, administered orally under fasted conditions.

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a real-world study involving 58 patients with hepatitis C virus genotype 1, a 12-week treatment with paritaprevir, ombitasvir, and ritonavir achieved a high sustained virological response (SVR) rate of 96.6%, demonstrating its efficacy even in patients with prior treatment failures.

The treatment was found to be safe, with only 26% of patients experiencing mild adverse events and no severe adverse events reported, indicating a favorable safety profile for patients with chronic hepatitis or compensated hepatic cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Real-world Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir for Hepatitis C Genotype 1. Miyasaka, A., Yoshida, Y., Yoshida, T., et al.[2021]

In the LIVIFY trial involving 120 patients with suspected fibrotic NASH, vonafexor significantly reduced liver fat content after 12 weeks, with the 100 mg and 200 mg doses showing reductions of -6.3% and -5.4% respectively, compared to -2.3% in the placebo group.

Vonafexor was found to be safe, leading to improvements in liver enzymes, body weight, and even renal function, although mild to moderate pruritus was reported in some patients, indicating manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. Ratziu, V., Harrison, SA., Loustaud-Ratti, V., et al.[2023]

Robuvit® supplementation for 3 months in patients with non-alcoholic fatty liver disease (NAFLD) significantly improved liver function markers, including decreased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating better hepatic metabolism.

The study, involving 34 subjects, showed that Robuvit® was well-tolerated with no side effects, and it also led to a significant reduction in liver size and echogenicity, suggesting a prevention of progression to liver fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Robuvit® on the progression of non-alcoholic fatty liver disease. Belcaro, G., Cox, DM., Cesarone, MR., et al.[2022]

In a study involving 16 participants (8 with moderate hepatic insufficiency and 8 healthy controls), the pharmacokinetics of a single 40-mg dose of laropiprant (LRPT) showed that patients with hepatic insufficiency had significantly higher exposure to the drug, with an estimated geometric mean ratio (GMR) of 2.78 for the area under the curve (AUC).

Despite the increased exposure, the single-dose LRPT was generally well tolerated in all participants, indicating that while hepatic insufficiency affects drug levels, it does not necessarily lead to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, in patients with moderate hepatic impairment. Wang, YH., Liu, F., Luk, JA., et al.[2018]

Cilofexor, a nonsteroidal FXR agonist, was well tolerated in a study of 120 healthy participants, with mild to moderate treatment-emergent adverse events, primarily headaches, indicating a favorable safety profile for further testing.

The drug effectively increased levels of FGF19 and reduced bile acids in a dose-dependent manner, suggesting its potential efficacy in treating conditions like NASH and PSC, with optimal FXR activation observed at doses above 30 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal Farnesoid X receptor agonist, in healthy volunteers. Younis, IR., Kirby, BJ., Billin, AN., et al.[2023]

The NATIVE study is a Phase 2b clinical trial assessing the safety and efficacy of lanifibranor, a panPPAR agonist, in treating non-cirrhotic non-alcoholic steatohepatitis (NASH) over 24 weeks, involving adult patients with specific histological criteria.

The primary goal is to achieve a 2-point reduction in the SAF histological score, indicating improved liver inflammation and ballooning without worsening fibrosis, highlighting lanifibranor's potential to address multiple aspects of NASH pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, placebo-controlled, multi-centre, dose-range, proof-of-concept, 24-week treatment study of lanifibranor in adult subjects with non-alcoholic steatohepatitis: Design of the NATIVE study. Sven M, F., Pierre, B., Manal F, A., et al.[2021]

A new class of hybrid molecules has been developed that acts as both antagonists of the cysteinyl leukotriene receptor 1 (CysLT1R) and agonists of the G protein bile acid receptor 1 (GPBAR1/TGR5), showing potential for treating nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

In preclinical models, the most effective compound demonstrated the ability to reverse liver damage and improve lipid and energy metabolism, indicating its efficacy in addressing the underlying issues of NAFLD/NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of a Potent and Orally Active Dual GPBAR1/CysLT1R Modulator for the Treatment of Metabolic Fatty Liver Disease. Fiorucci, S., Rapacciuolo, P., Fiorillo, B., et al.[2022]

In a trial involving 36 patients with non-alcoholic fatty liver disease (NAFLD), the pan-phosphodiesterase inhibitor ZSP1601 was found to be well-tolerated, with 75% of participants experiencing mild to moderate treatment-emergent adverse events, but no serious adverse events reported.

ZSP1601 demonstrated effective improvements in liver chemistries, liver fat content, and fibrosis, suggesting it could be a promising treatment option for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial. Hu, Y., Li, H., Zhang, H., et al.[2023]

In a phase 3 trial involving 363 Japanese patients with hepatitis C virus genotype 1b, a 12-week treatment regimen of coformulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) achieved a high sustained virological response rate of 94.6% in patients without cirrhosis.

The treatment demonstrated a favorable safety profile, with a low discontinuation rate due to adverse events (0%-2.4%) and the most common side effect being nasopharyngitis, indicating that OBV/PTV/r is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Kumada, H., Chayama, K., Rodrigues, L., et al.[2022]

Compound 32 (BMS-986339) is a novel FXR agonist that shows potent activation of the farnesoid X receptor, with tissue-selective effects that may lead to fewer side effects compared to other FXR agonists.

In preclinical studies, Compound 32 demonstrated strong antifibrotic efficacy in treating nonalcoholic steatohepatitis (NASH) while potentially reducing adverse effects like pruritus and elevated plasma lipids, suggesting it could be a safer alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis. Nara, SJ., Jogi, S., Cheruku, S., et al.[2022]

The multicentric observational study compared the effects of obeticholic acid and fibrates in patients with primary biliary cholangitis, highlighting their efficacy in managing this liver disease.

Results indicated that obeticholic acid may provide superior benefits in improving liver function tests compared to fibrates, suggesting it could be a more effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing Medical Education Questions: November 2021. Richter, SJ.[2023]

In a phase 2 trial involving 140 patients with nonalcoholic steatohepatitis (NASH), cilofexor 100 mg daily for 24 weeks significantly reduced liver fat content by 22.7% compared to a placebo, indicating its efficacy in treating hepatic steatosis.

Cilofexor was generally well-tolerated, although moderate to severe itching was reported more frequently in the 100 mg group (14%) compared to the lower dose and placebo, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Patel, K., Harrison, SA., Elkhashab, M., et al.[2021]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06340347

NCT06340347 | A Study to Learn How the Body Processes ... The purpose of this study is to understand how Osivelotor is processed in people with loss of liver function. This study is seeking participants that are:.

2. synapse.patsnap.com synapse.patsnap.com/drug/b5468d15ffb34015ad8127398f581b53

Osivelotor - Drug Targets, Indications, Patents This review summarizes the characteristics and primary results obtained with osivelotor, a novel oxygen affinity modulator, for the treatment of SCD.

3. sigma.larvol.com sigma.larvol.com/product.php?e1=947935&tab=newstrac

osivelotor (PF-07940367) News These preliminary PD results from patients with SCD suggest promising evidence of improved RBC health and blood flow following osivelotor treatment. Overall, ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06340347/a-study-to-learn-how-the-body-processes-the-study-medicine-called-osivelotor-pf-07940367-in-people-with-loss-of-liver-function

A Study to Learn How the Body Processes ... The purpose of this study is to understand how Osivelotor is processed in people with loss of liver function.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40832524/

Discovery of Osivelotor (GBT021601): A Potent, Next- ... GBT021601 has ∼4.8-fold greater exposure and a ∼3.5-fold longer half-life in rats compared with voxelotor. In a murine model of sickle cell ...

6. withpower.com withpower.com/trial/phase-1-liver-diseases-3-2024-f7f2d

Osivelotor for Liver Disease · Info for Participants What safety data is available for Osivelotor in treating liver disease? The provided research does not contain specific safety data for Osivelotor (also ...

7. pfizerclinicaltrials.com pfizerclinicaltrials.com/sites/default/files/2024-09/2022-06-09_GBT_EHA%202022%20601.pdf

Safety, Tolerability, and GBT021601 is a next-generation HbS polymerization inhibitor with improved PK properties. GBT021601 has the potential to achieve higher Hb occupancies at lower ...