A Phase I/II study of TGM-312-SC01 in healthy participants and adults with metabolic dysfunction-associated steatohepatitis
| ISRCTN | ISRCTN65253349 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN65253349 |
| Integrated Research Application System (IRAS) | 1012956 |
| Central Portfolio Management System (CPMS) | 70891 |
| Sponsor | Tangram Therapeutics plc |
| Funder | Tangram Therapeutics plc |
- Submission date
- 05/02/2026
- Registration date
- 13/02/2026
- Last edited
- 13/02/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease and is characterized by excessive accumulation of fat in the liver, also known as hepatic steatosis, in the absence of excessive alcohol intake. As MASLD patients progress in their disease, they develop inflammation, fibrosis (scarring of the liver tissue), and cirrhosis that can lead to liver failure. Numerous factors and conditions contribute to the underlying mechanisms of the disease, including central obesity, insulin resistance, lipid metabolism, liver function, dietary influences, the composition of intestinal microbiota, and genetic factors. Progression to metabolic dysfunction-associated steatohepatitis (MASH), the more severe form of MASLD, is promoted by lipotoxic insults driving hepatocyte (liver cells) injury, inflammation, and chronic activation of wound healing responses. The study aims to see if TGM-312-SC01, a possible treatment for MASH, is safe in healthy volunteers and people with MASH and also to see if there is any initial signs that the treatment may shows signs of working in people with MASH.
Who can participate?
Participants aged 18 years to 70 years: healthy volunteers in Part A and patients with MASH in Parts B and C
What does the study involve?
Participants will be randomly allocated to receive either TGM-312-SC01 or placebo via subcutaneous injection (an injection into a person’s fat tissue). For Part A, participants would receive one dose of the trial treatment and for Parts B and C participants would receive two doses of the trial treatment, 4 weeks apart. All participants will be followed up for 16 weeks after their last dose of the trial treatment and will visit the research site up to seven times to complete study assessments such as blood sampling, vital signs, physical examinations and imaging performed on the liver. Participants in Parts B and C will have a liver biopsy on two occasions, performed before trial treatment and at the end of the study.
What are the possible benefits and risks of participating?
This is a first in human study, the trial cannot guarantee that there will be any benefit to participants with MASH as it is unknown at this stage. For the healthy participants in Part A, there is no expectation of benefit from taking part.
The risks of taking the trial drug are unknown as this drug has never been given to people before. There are risks involved in some of the study procedures including bruising at the injection site or from blood sampling. Liver biopsies are associated with a small risk of complication for participants in Parts B and C of the study. These include pain at the biopsy site, temporary low blood pressure and mild bleeding.
Where is the study run from?
Part A of the study will be run at Richmond Pharmacology Clinical Research Unit London (UK) and Parts B and C of the study will be run from King's College Hospital Research Unit, London (UK).
When is the study starting and how long is it expected to run for?
February 2026 to September 2028
Who is funding the study?
Tangram Therapeutics (UK)
Who is the main contact?
clinicaltrials@tangramtx.com
Contact information
Principal investigator
Richmond Pharmacology Clinical Trial Unit
1a Newcomen Street
London Bridge
London
SE1 1YR
United Kingdom
| Phone | +44 (0)20 7042 5800 |
|---|---|
| j.taubel@richmondpharmacology.com |
Public
Tangram Therapeutics
4B, 4th Floor
4 Kingdom Street
London
W2 6BD
United Kingdom
| Phone | +44 (0)20 4558 3826 |
|---|---|
| clinicaltrials@tangramtx.com |
Scientific
Tangram Therapeutics
4B, 4th Floor
4 Kingdom Street
London
W2 6BD
United Kingdom
| Phone | +44 (0)20 4558 3826 |
|---|---|
| clinicaltrials@tangramtx.com |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Blinded (masking used) |
| Control | Placebo |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | A first-in-human, Phase I/II, randomized, masked, placebo-controlled, parallel-group, dose-escalation, adaptive study to evaluate the safety and pharmacokinetics of a single dose of TGM-312-SC01 in healthy participants and the safety, pharmacokinetics, pharmacodynamics and early signs of efficacy of multiple doses of TGM-312-SC01 in people with metabolic dysfunction-associated steatohepatitis (MASH) |
| Study acronym | RESTORE-MASH |
| Study objectives | |
| Ethics approval(s) |
Approved 30/01/2026, South Central - Berkshire B Research Ethics Committee (Health Research Authority, 2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 1048276; berkshireb.rec@hra.nhs.uk), ref: 25/SC/0352 |
| Health condition(s) or problem(s) studied | Metabolic dysfunction-associated steatohepatitis (MASH) |
| Intervention | Participants will receive either the trial medication (TGM-312-SC01) or placebo via subcutaneous injection. Participants will be randomised to receive TGM-312-SC01 or placebo in a 1:1 ratio in Part A and 2:1 ratio for Parts B and C. Participants in Part A will receive the trial treatment once, participants in Parts B and C will receive the trial treatment twice, 4 weeks apart. Doses for Part A are proposed as 15, 45, 100, 200, 400 and 600 mg. The dose for Part B/C will decided upon review of the data from Part A. |
| Intervention type | Drug |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | TGM-312-SC01 |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
1. Pharmacokinetics of TGM-312-SC01 measured using blood sampling at predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours (Part A) |
| Completion date | 06/09/2028 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | All |
| Target sample size at registration | 99 |
| Key inclusion criteria | 1. Adults aged 18 to 70 years 2. Able to provide written informed consent 3. Medically suitable for study participation based on protocol-defined assessments For the disease cohort, participants must have clinical features consistent with metabolic dysfunction-associated steatohepatitis, as defined in the protocol |
| Key exclusion criteria | 1. Clinically significant medical conditions, laboratory abnormalities, or other findings that, in the opinion of the investigator, could increase risk, interfere with study participation, or confound interpretation of study results 2. Recent participation in another investigational study 3. Use of medications that are prohibited by the protocol 4. Any other condition that would make the individual unsuitable for study participation as determined by the investigator |
| Date of first enrolment | 16/02/2026 |
| Date of final enrolment | 05/04/2028 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
London
SE5 9RS
England
London Bridge
London
SE1 1YR
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan |
Editorial Notes
12/02/2026: Study's existence confirmed by the South Central - Berkshire B Research Ethics Committee.
