RTX001 Autologous Engineered Macrophages for Liver Cirrhosis

NCT06823713 | Recruiting Phase 1 DMC

• 2 other identifiers: RTX001-0022024-516288-10
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 14

Brief Summary

The purpose of this study is to assess the safety and efficacy of RTX001 in patients with end-stage liver disease. This study is the first time RTX001, a macrophage cell therapy engineered to have an anti-inflammatory and anti-fibrotic effect, will be given to humans.

Conditions

End-stage Liver Disease (ESLD); Cirrhosis, Liver; Cirrhosis, Decompensated; Liver Diseases; Fibrosis and Cirrhosis of Liver; Decompensated Liver Cirrhosis; Decompensated Cirrhosis; Steatotic Liver Disease

Keywords

Liver cirrhosis; Cirrhotic; Hepatic Cirrhosis; Chronic Liver Disease; Liver Fibrosis; Decompensated Liver Cirrhosis; Child-Pugh Score; MELD Score; Liver Function Tests; Hepatic Encephalopathy; End Stage Liver Disease (ESLD); Variceal Bleeding; Jaundice; Retractable Ascites; Autologous; Cell Therapy; Macrophage; Steatotic Liver Disease

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability

  Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

  2.5 years

• Safety and Tolerability

  Incidence and severity of infusion reactions

  At each infusion; day of infusion up to two weeks post-infusion

Secondary Outcomes (3)

• Time to clinical event

  2.5 years

• Time to mortality

  2.5 years

• Change in Model for End Stage Liver Disease score 3.0 (MELD3.0)

  2.5 years

Study Arms (1)

RTX001

EXPERIMENTAL

Following the manufacture of RTX001, participants will be assigned into one of two groups based on the compensation status of their cirrhosis at this time as follows: * Stabilised Group: Participants who remain clinically stable, as assessed by the Investigator, since their qualifying decompensation event. * Subsequent Decompensation Group: Participants who have had a further decompensation event following their leukapheresis and/or the RTX001 manufacturing process. Treatment will be identical for both groups, and each participant will receive a maximum of four doses of RTX001 by intravenous infusion Patients in the Subsequent Decompensation Group need to have stabilised before receiving treatment.

Drug: RTX001

Interventions

RTX001 DRUG

RTX001 is an autologous engineered regenerative macrophage cell therapy

RTX001

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age ≥18-75 years.
• Patient confirms willingness/ability to comply with all study procedures.
• Diagnosis of liver cirrhosis based on at least one of:
• Clinical and radiological features that correlate with a diagnosis of cirrhosis.
• Transient elastography (Fibroscan) \>15 kPa.
• Previous liver biopsy confirming histological features of cirrhosis.
• Aetiology of liver disease of steatotic liver disease including MASLD or Met-ALD or ALD
• a. Participants with alcohol-related liver disease (ALD or Met-ALD) only if they are confirmed to not be drinking alcohol above Met-ALD limits defined in this protocol. (N.B. No more than 34% of the total treated participants in this protocol will be ALD \[excludes Met-ALD\]).
• Hospitalised as an inpatient for a recent major hepatic decompensation event including ascites, hepatic encephalopathy, variceal bleed, HRS-AKI or SBP, this being the only hospitalisation for an hepatic decompensation event hospitalisation within the last 6 months, and where recent is defined as within 6 weeks of hospital discharge.
• Outpatient: Medically refractory ascites (ONLY), that recurs (i.e., second therapeutic LVP) within a 6-month period. Medically refractory ascites is defined by the repeated (≥2) need for LVP (i.e., therapeutic, not diagnostic) at least once per 8 weeks despite best medical attempts to control the ascites by sodium restriction and diuretic treatment, as confirmed by the Investigator. Onset is defined as the date of the second therapeutic LVP.
• Confirmatory PEth alcohol test \<200 ng/ml
• MELD score of 12-20 taken within two weeks of 'qualifying' decompensation event.
• No known contradictions to filgrastim or leukapheresis procedure.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Willing and able to give signed informed consent, and if applicable assent.

You may not qualify if:

• Liver cirrhosis due to:
• any viral hepatitidies, or
• autoimmune and cholestatic aetiologies including, but not limited to, primary biliary cholangitis and primary sclerosing cholangitis.
• Acute liver disease in the absence of underlying liver cirrhosis, including, but not limited to, drug induced liver injury.
• Any current organ failure requiring more than outpatient supportive care, and not associated with the participant's qualifying hepatic decompensation event.
• Known splenomegaly ≥16 cm.
• Thrombocytopenia \<50×109/L.
• Presence or suspicion of any of the following co-morbidities:
• History of liver transplantation or other organ transplant.
• ACLF.
• Sepsis (with positive microbial cultures) or as defined by the Principal Investigator, unless stable and is at least 4 weeks after having completed a full course of IV antibiotics.
• Known human immunodeficiency virus.
• Known syphilis.
• Known human T-lymphotropic virus 1.
• Pulmonary embolism.

Sponsors & Collaborators

• Resolution Therapeutics Limited: lead

Study Sites (14)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Bristol Royal Infirmary

Bristol, BS2 8HW, United Kingdom

RECRUITING

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

RECRUITING

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

RECRUITING

Royal Liverpool University Hospital

Liverpool, L7 8YE, United Kingdom

RECRUITING

King's College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

St George's Hospital

London, SW17 0QT, United Kingdom

RECRUITING

St Mary's Hospital

London, W2 1NY, United Kingdom

RECRUITING

Nottingham University Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Related Publications (4)

• Forbes S et al., Hepatology. AASLD Abstract #0095 (2024)

  BACKGROUND

• Brennan et al., Hepatology. AASLD Abstract #160 (2023) https://www.aasld.org/the-liver-meeting/open-label-parallel-group-phase-ii-randomised-controlled-trial-autologous

  BACKGROUND

• LBP-007 Beneficial effects of autologous macrophage therapy on clinical outcomes in patients with compensated cirrhosis: extended follow-up data from a randomized controlled phase 2 trial Brennan, Paul et al. Journal of Hepatology, Volume 80, S81 DOI: 10.1016/S0168-8278(24)00574-9

  BACKGROUND

• Moroni F, Dwyer BJ, Graham C, Pass C, Bailey L, Ritchie L, Mitchell D, Glover A, Laurie A, Doig S, Hargreaves E, Fraser AR, Turner ML, Campbell JDM, McGowan NWA, Barry J, Moore JK, Hayes PC, Leeming DJ, Nielsen MJ, Musa K, Fallowfield JA, Forbes SJ. Safety profile of autologous macrophage therapy for liver cirrhosis. Nat Med. 2019 Oct;25(10):1560-1565. doi: 10.1038/s41591-019-0599-8. Epub 2019 Oct 7.

  PMID: 31591593 BACKGROUND

Related Links

• The OPAL Study on ClinicalTrials.gov
• British Liver Trust - The EMERALD Study

MeSH Terms

Conditions

End Stage Liver Disease; Liver Cirrhosis; Fibrosis; Liver Diseases; Hepatic Encephalopathy; Jaundice

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperbilirubinemia; Skin Manifestations; Signs and Symptoms

Central Study Contacts

Resolution Therapeutics Clinical Enquiries

CONTACT

+442037811105; clinical.enquiries@resolution-tx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2024
• First Posted: February 12, 2025
• Study Start: October 15, 2024
• Primary Completion (Estimated): August 29, 2028
• Study Completion (Estimated): November 29, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

ES (6); GB (8)