RTX001 for Liver cirrhosis|Decompensated liver cirrhosis

Inclusion criteria

• {"criterion_text":"- 1. Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent form (ICF)\n- 10. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.\n- 11. Willing and able to give signed informed consent, and if applicable assent, as described in Section 8.1, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.\n- 2. Participant confirms willingness/ability to comply with all study procedures.\n- 3. Diagnosis of liver cirrhosis based on at least one of: a. Clinical and radiological features that correlate with a diagnosis of cirrhosis. b. Transient elastography (Fibroscan®) >15 kPa. c. Previous liver biopsy confirming histological features of cirrhosis.\n- 4. 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]).\n- 5. 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 OR\n- 6. 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.\n- 7. Confirmatory PEth alcohol test <200 ng/ml\n- 8. MELD 3.0 score of 12-20 (inclusive) taken within 2 weeks of ‘qualifying’ decompensation event. If the participant qualifies as an outpatient then they must have a MELD 3.0 score of 12-20 (inclusive) at the time of the screening (Visit 1).\n- 9. No known contradictions to filgrastim or leukapheresis procedure."}

Exclusion criteria

• {"criterion_text":"- 1. Liver cirrhosis due to: a. any viral hepatitidies b. autoimmune and cholestatic aetiologies including, but not limited to, primary biliary cholangitis and primary sclerosing cholangitis.\n- 10. Current or planned use of a live attenuated vaccines four weeks or fewer prior to enrolment (and for 3 months after the last administered dose of RTX001).\n- 11. Received any investigational product within the past 6 months, or five half-lives (whichever is longer) or participated in another investigational interventional study within 30 days prior to the screening visit.\n- 12. Participants with a known hypersensitivity to dimethyl sulfoxide (DMSO).\n- 13. Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.\n- 14. For female participants only – pregnant or breast-feeding or plans to become pregnant over the next year, or of childbearing potential and unwilling to comply with contraceptive requirements\n- 15. Alcohol misuse in the period between identification of the participant as potentially suitable for this study to Screening (Visit 1), defined as alcohol intake greater than three units/day for females and four units/day for males, or binge drinking (>14 units/day) as determined by the Investigator. N.B. One unit is equivalent to 14 g of alcohol: a half-pint (~240 mL) of beer, one glass (125 mL) of wine or one (25 mL) measure of spirits.\n- 16. Intake of non-medically supervised drugs of abuse that are judged (by the Investigator) to be a high risk to the participants acute health or which makes the participant likely to be non-compliant with follow-up.\n- 2. Acute liver disease in the absence of underlying liver cirrhosis, including, but not limited to, drug induced liver injury.\n- 3. Any current organ failure requiring more than outpatient supportive care, and not associated with the participant’s qualifying hepatic decompensation event.\n- 4. Known splenomegaly ≥16 cm.\n- 5. Thrombocytopenia <50×109/L.\n- 6. Presence or suspicion of any of the following co-morbidities: a. History of liver transplantation or other organ transplant. b. ACLF. c. 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. d. Known human immunodeficiency virus. e. Known syphilis. f. Known human T-lymphotropic virus 1. g. Pulmonary embolism. h. Hepatocellular carcinoma, or any active malignant disease within the last five years, (excluding non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, benign polyps etc.). i. Co-hepatic morbidities e.g., portal vein thrombosis. j. Participants with hepatic hydrothorax are excluded unless it is a small hydrothorax, not clinically apparent, that is detected incidentally by radiologic evaluation that does not require clinical intervention. k. Chronic renal impairment (on dialysis) or unresolved AKI. l. Acute or chronic heart failure (New York Heart Association Grade III/IV). m. Porto-pulmonary hypertension. n. Severe chronic lung disease e.g., chronic obstructive pulmonary disease or interstitial lung disease where the forced expiratory volume in the first second (FEV1) is less than 50% and/or FEV1/forced vital capacity (FVC) is less than 60%. o. Hepatopulmonary syndrome. p. Previous or current treatment with long-term multiple infusions of albumin for therapeutic intent. [Use of albumin infusion at the time of large volume paracentesis for circulatory support is allowed.] q. Significant untreated/unstable psychiatric disease. r. Transjugular intrahepatic portosystemic shunt (TIPSS)\n- 7. As judged by the Investigator, any evidence of intercurrent illness that is either life threatening or of clinical significance such that it might limit compliance with study procedures.\n- 8. Current or planned use of immunomodulators or immunosuppressive medication; note: low doses of corticosteroids up to 10 mg per day prednisone or equivalent are permitted, or inhaled steroids to manage asthma.\n- 9. Received a gene or cell therapy at any time."}

Primary endpoints

• {"endpoint_text":"- 1. Incidence and severity of TEAEs and SAEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- 2. Changes from baseline in safety assessments","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3. Incidence and severity of infusion reactions","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Time-to, incidence and severity of: 1. Development of a second portal hypertension-driven decompensating event (ascites, variceal haemorrhage or hepatic encephalopathy).","definition_or_measurement_approach":""}
• {"endpoint_text":"- 2. Development of recurrent variceal bleeding, recurrent ascites (requirement of ≥3 large-volume paracenteses within 1 year), recurrent encephalopathy, development of SBP and/or HRS-AKI","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3. In participants presenting with bleeding alone, development of ascites, or encephalopathy, after recovery from bleeding (but not if these events occur around the time of bleeding)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 4. All hepatic decompensation events including SBP and/or HRS-AKI, new listing for liver transplantation or liver transplantation","definition_or_measurement_approach":""}
• {"endpoint_text":"- 5. Mortality (hepatic related and all-cause), transplant-free survival.","definition_or_measurement_approach":""}
• {"endpoint_text":"- 6. ΔMELD, ΔΔMELD and MELD stabilisation","definition_or_measurement_approach":""}

Methods

• Site posters at participating hospitals (K2_Recruitment Material_Site Poster)
• Social media posts (Facebook, Instagram, X) (multiple K2_Social Media Post documents)
• Patient information brochure (K2_FNETH_Patient brochure; K2_Recruitment Material_Patient Information Brochure_Redacted)
• Webpage (K2_FNETH Webpage_Redacted)
• Video storyboard (K2_Recruitment material_Video Story board_Redacted)
• Study overview flipchart (K2_Recruitment Material_Study overview flipchart_Redacted)
• MATCH Study Infographic (K2_Recruitment material_MATCH Study Infographic)

Spain

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

534

Number Of Sites

8

Number Of Participants

8

Primary sponsor

Full Name

Resolution Therapeutics Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Fortrea Belgium

Responsibilities

Vendor Management, Biostats, DSMC, TMF, Medical Monitoring, Pharmacovigilance, Call center, Materials (sponsorDuties includes codes and value as listed)

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties: code 3

Name

Medidata Solutions Inc.

Responsibilities

sponsorDuties: code 4

Name

Labcorp Central Laboratory Services SARL

Responsibilities

sponsorDuties: code 4 (central laboratory services)

Name

NMS Laboratories

Responsibilities

sponsorDuties: code 4

Third parties

• {"country":"United Kingdom","full_name":"AttoLife","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Resolution Therapeutics Limited (EMERALD.lab)","duties_or_roles":"sponsorDuties: code 15 (Biomarker Analysis)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"sponsorDuties: code 15 (Meeting Planners)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Greens","duties_or_roles":"sponsorDuties: code 15 (Printing)","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties: code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties: code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Scottish National Blood Transfusion Service","duties_or_roles":"sponsorDuties: code 15 (Infectious Disease Marker Tests)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Fortrea Belgium","duties_or_roles":"sponsorDuties: code 1; code 10; code 11; code 12; code 15 (Vendor Management, Biostats, DSMC, TMF, Medical Mon', Pharmacovigilance, Call center, Materials); code 2; code 5; code 6; code 7; code 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"NMS Laboratories","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Industry"}