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NOT YET RECRUITING

NCT05491135

PHASE1/PHASE2

Hepatocyte Microbeads for Acute Liver Failure

Sponsor: King's College Hospital NHS Trust

View on ClinicalTrials.gov

Summary

Acute Liver Failure in children is associated with high mortality without liver transplantation. In addition, donor organ shortage makes it difficult to provide this treatment to every potential patient. Liver transplantation is life-saving but it carries the risk of major surgery and complications from lifelong anti-rejection drugs to suppress the immune system. If bridged across the immediate crisis following acute liver failure, the immense regenerative potential of the liver means that the patient's own liver may 're-grow'. This period is very time sensitive. Unfortunately, if the vital synthetic and detoxification function of the liver is not provided, the patient will often die before the liver can re-grow. Transplantation of liver cells (hepatocytes) can provide this 'bridge' with considerable advantages over whole organ transplantation. Firstly, hepatocytes are derived from donor livers which are otherwise unsuitable for transplantation. Secondly, unlike whole organs, they can be frozen and stored, thus act as an 'off the shelf' treatment. Thirdly, the technique of hepatocyte transplantation within microbeads coated with alginate (a gel originating from seaweed) and infused into the abdominal cavity is much less invasive than liver transplantation. Finally, the alginate protects the cells against the body's immune system, avoiding the need for immunosuppressive drugs and the associated major risks. Furthermore, preclinical work in King's College Hospital has shown that the addition of support cells called mesenchymal stromal cells (MSCs), can significantly improve the ability of hepatocytes to survive and function within the alginate microbead. The HELP trial is a Phase 1/2 safety and tolerability study of infusion of HMB002 (an optimal combination of hepatocytes and mesenchymal stromal cells put together in peptide-alginate microbeads) into paediatric patients with acute liver failure. This novel cellular therapy may act as a bridge treatment to liver transplant or lead to regeneration of the native liver.

Official title: Hepatocytes Co-Encapsulated With Mesenchymal Stromal Cells in Alginate Microbeads for the Treatment of Acute Liver Failure in Paediatric Patients (HELP)

Key Details

Gender

All

Age Range

Any - 16 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2022-09

Completion Date

2026-05

Last Updated

2022-08-08

Healthy Volunteers

Conditions

Acute Liver Failure

Interventions

BIOLOGICAL

HMB002

The solution containing microbeads will be infused manually into the peritoneal cavity under ultrasound guidance, with usually a 50ml syringe, as a single infusion or several infusions, to achieve in excess of 25 million hepatocytes per kilogram of the body weight.

Inclusion Criteria: * Infant or child (male or female) under the age of 16 years at recruitment. * Written informed consent obtained from a parent / legal guardian * Presence of ALF defined as a multisystemic disorder in which severe impairment of liver function with or without encephalopathy occurs in association with hepatocellular necrosis reflected as synthetic liver failure in a child with no recognised underlying chronic liver disease. Children must fit one of the ALF categories as described in Appendix 1b(study protocol); * Willing and able to comply with the study visit schedule. Exclusion Criteria: * Severe ascites causing high intra-abdominal pressure and / or respiratory compromise; * Intra-abdominal sepsis suspected or proven; * Clinical condition too unstable to tolerate procedure without compromise; * Proven pre-existing allergy or intolerance to alginate on medical history; * Proven pre-existing allergy to gentamicin on medical history; * Intraperitoneal or intra-abdominal malignancy; * Adhesions or fistulae to anterior abdominal wall; * Children who weigh in excess of 33kg * Pregnant or lactating patients (positive pregnancy test for females of child bearing potential at screening). * Female patients of childbearing potential who are not willing to use highly effective methods of contraception to prevent pregnancy or abstain from heterosexual activity for 52 weeks post treatment. \*Females of child bearing potential are females who have experienced menarche and are not surgically sterilised (e.g. by tubal occlusion, hysterectomy, bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). \*\* Highly effective methods of birth control are those with a failure rate of \< 1% per year when employed consistently and correctly. Highly effective methods of contraception as per HMA / CTFG working group are combined (Estrogen and Progestogen containing) hormonal contraception associated with inhibition of ovulation, the preparation may be oral, intravaginal or transdermal; progesterone-only hormonal contraception associated with inhibition of ovulation which may be oral, injectable or implantable; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence for 52 weeks post study treatment; \*\*\* Sexual abstinence is considered to be highly effective method only if defined as refraining from heterosexual activity from the date of consent until the week 52 visit post study treatment. The reliability of this method should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. * Male patients who are not willing to use an effective method of contraception (condom, vasectomy, sexual abstinence) for 52 weeks post study treatment, when engaging in sexual activity with a female of childbearing potential; * Participation in concurrent therapeutic trial for ALF; * Imminent liver transplantation expected within 12 hours of infusion; * Total hepatectomy; * Dependent on Extracorporeal Membrane Oxygenation (ECMO); * Previous liver transplant