A safety and efficacy study of RTX001 autologous macrophage therapy in participants with decompensated liver cirrhosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Resolution Therapeutics Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 Mar 2025 → ongoing

Decision date (initial)

2024-11-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Resolution Therapeutics Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety and tolerability of RTX001 in the Stabilised Group participants.

Secondary objectives 3

1. 1. To evaluate the clinical efficacy of RTX001 in the Stabilised Group participants
2. 2. To evaluate changes in MELD scores, from baseline to end of study, in the Stabilised Group participants
3. 3. To compare and evaluate the characteristics and morbidities of the Stabilised Group participants after treatment

Conditions and MedDRA coding

Liver Cirrhosis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Agencia Espanola De Medicamentos Y Productos Sanitarios

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent form (ICF)
2. 2. Participant confirms willingness/ability to comply with all study procedures.
3. 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.
4. 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]).
5. 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
6. 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.
7. 7. Confirmatory PEth alcohol test <200 ng/ml
8. 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).
9. 9. No known contradictions to filgrastim or leukapheresis procedure.
10. 10. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
11. 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.

Exclusion criteria 16

1. 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.
2. 2. Acute liver disease in the absence of underlying liver cirrhosis, including, but not limited to, drug induced liver injury.
3. 3. Any current organ failure requiring more than outpatient supportive care, and not associated with the participant’s qualifying hepatic decompensation event.
4. 4. Known splenomegaly ≥16 cm.
5. 5. Thrombocytopenia <50×109/L.
6. 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)
7. 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.
8. 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.
9. 9. Received a gene or cell therapy at any time.
10. 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).
11. 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.
12. 12. Participants with a known hypersensitivity to dimethyl sulfoxide (DMSO).
13. 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.
14. 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
15. 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.
16. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Incidence and severity of TEAEs and SAEs
2. 2. Changes from baseline in safety assessments
3. 3. Incidence and severity of infusion reactions

Secondary endpoints 6

1. Time-to, incidence and severity of: 1. Development of a second portal hypertension-driven decompensating event (ascites, variceal haemorrhage or hepatic encephalopathy).
2. 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
3. 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)
4. 4. All hepatic decompensation events including SBP and/or HRS-AKI, new listing for liver transplantation or liver transplantation
5. 5. Mortality (hepatic related and all-cause), transplant-free survival.
6. 6. ΔMELD, ΔΔMELD and MELD stabilisation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Resolution Therapeutics Limited

Sponsor organisation

Resolution Therapeutics Limited

Address

245 Hammersmith Road

City

London

Postcode

W6 8PW

Country

United Kingdom

Scientific contact point

Organisation

Resolution Therapeutics Limited

Contact name

Chief Medical Officer​, Dr Cliff Brass MD​

Public contact point

Organisation

Resolution Therapeutics Limited

Contact name

Esther Kitto

Third parties 10

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications