* 1404-0043 Combined PhIIa/b in NASH
Research type
Research Study
Full title
Multicenter, double-blind, parallel-group, randomised, 48 weeks, dose-ranging, placebo-controlled phase II trial to evaluate efficacy, safety and tolerability of multiple subcutaneous (s.c.) doses of BI 456906 in patients with non-alcoholic steatohepatitis (NASH) and fibrosis
IRAS ID
291539
Contact name
Philip Newsome
Contact email
Sponsor organisation
Boehringer Ingelheim Limited
Eudract number
2020-002723-11
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 7 months, 26 days
Research summary
This study is a phase II study to test whether different doses of BI 456906 are effective in people with a liver disease called non-alcoholic steatohepatitis (NASH) who also have liver scarring (fibrosis). This dose-finding trial is important to assess the most suitable dose to take forward in the later phase III/IV trial, in which histological improvement as well as long-term clinical outcomes will be evaluated. The population will include male and female participants aged 18 and over with a diagnosis of NASH (NAS ≥ 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F1–F3 as demonstrated on a liver biopsy. Patients with a history of significant alcohol consumption or recent intake of medications historically associated with liver injury will be excluded from the study. There are 4 treatment groups receiving different doses of 2.4, 4.8 and 6.0 mg as well as a placebo group. It is planned that, globally, a total of 240 patients will be randomised into the study and each treatment group will consist of 60 patients.
Group 1 will receive a starting dose of 0.3 mg followed by a dose escalation up to the maintenance dose of 2.4 mg, Group 2 will receive a starting dose of 0.3 mg followed by a dose escalation up to the maintenance dose of 4.8 mg, Group 3 will receive a starting dose of 0.3 mg followed by a dose escalation up to the maintenance dose of 6.0 mg, all groups will be dosed with two pre-filled syringes once weekly. The study involves 48 weeks of treatment consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period ending with a four week follow up period.LAY SUMMARY OF STUDY RESULTS:
After 48 weeks of treatment, up to 64% of participants in the survodutide groups had improvement in their NASH and liver fibrosis compared to the 15% of participants in the placebo group.
We did statistical tests on the results. We found that it was unlikely that the differences between each survodutide dose group and the placebo group were due to chance.
These results showed that survodutide may help people with NASH and liver fibrosis.Did participants have any unwanted effects?
Yes, participants in all groups had unwanted effects. Unwanted effects are health problems that the doctors think were caused by the study medicine.
In this study,
- 174 out of 214 participants (81%) in all survodutide dose groups had unwanted effects.
- 41 out of 79 participants (52%) in the placebo group had unwanted effects.
The listing below shows the most common unwanted effects in all survodutide dose groups and the placebo group. The table also shows how many participants in each group had each of these unwanted effects.
Nausea:
- All survodutide dose groups (214 participants): 128 participants (60%)
- Placebo group (79 participants): 19 participants (24%)
Diarrhoea:
- All survodutide dose groups (214 participants): 83 participants (39%)
- Placebo group (79 participants): 14 participants (18%)
Vomiting:
- All survodutide dose groups (214 participants): 74 participants (35%)
- Placebo group (79 participants): 5 participants (6%)
Decreased appetite:
- All survodutide dose groups (214 participants): 37 participants (17%)
- Placebo group (79 participants): 7 participants (9%)
Swelling of the belly (abdominal distension):
- All survodutide dose groups (214 participants): 27 participants (13%)
- Placebo group (79 participants): 6 participants (8%)
Indigestion (dyspepsia):
- All survodutide dose groups (214 participants): 27 participants (13%)
- Placebo group (79 participants): 2 participants (3%)
In this study, 1 out of 214 participants (less than 1%) in all survodutide dose groups had a serious unwanted effect of swelling underneath the skin (angioedema). Unwanted effects are serious because they were life-threatening or the doctor thought they were serious for any other reason. This participant belonged to the low-dose survodutide group.REC name
London - South East Research Ethics Committee
REC reference
21/FT/0026
Date of REC Opinion
24 Mar 2021
REC opinion
Further Information Favourable Opinion