Phase IIb Efficacy and Safety Study of SOM3355 in Huntington’s Disease
Research type
Research Study
Full title
Phase IIb, randomized, double-blind, placebo-controlled study in parallel groups assessing the efficacy and safety of two doses of SOM3355 in patients suffering from Huntington’s Disease with choreic movements.
IRAS ID
1004824
Contact name
Aileen Ferré
Contact email
Sponsor organisation
SOM Innovation Biotech SA (SOM Biotech)
Eudract number
2021-003453-28
Clinicaltrials.gov Identifier
Research summary
This is an international, multicentre, double-blind, randomized, placebo-controlled Phase 2b study assessing two doses of SOM3355 (400 or 600 mg/day), in patients with choreic symptoms related to Huntington’s Disease (HD). HD is an inherited progressive neurodegenerative disease. Chorea is an involuntary jerky movement that is purposeless and abrupt and one of the most prominent symptoms in HD. SOM Biotech are funding this research which will recruit participants who are presenting with choreic symptoms related to HD and are not younger than 21 years old. The study drug – SOM3355 – has been marketed by Nippon Chemiphar since 1997 in Japan and South Korea (as Calvan®) to treat hypertension. The cumulative number of patients exposed up to February 2021 is estimated as more than 2.5 million patients. SOM3355 might bring advantages to treat choreic symptoms related to HD with a better safety profile than similar existing drugs. In this trial, 129 patients will be given either 400 or 600 mg/day of study drug (taken orally as two or three 100 mg tablets twice per day) or placebo to be taken at home for a total of 12 weeks. Each patient will be expected to attend the trial centre 7 times. The study is being run in hospitals in France, Germany, Italy, Poland, Spain, Switzerland and the United Kingdom and is expected to complete recruiting patients after one year.
SOM InnovationBiotech SA carried out the research.
What public involvement was in the study (how many people, what their relevant lived experience was, and what they did):
139 total patients with Huntington's disease (HD) participated in the trial during a maximum of 13 weeks, attended 7 visits to be treated with SOM3355 (active drug) or placebo (inactive treatment) to assess their response on chorea and other aspects of the disease.
Where and when the study took place:
Study was conducted in 23 investigational sites in countries, including France, Germany, Italy, Poland, Spain, Switzerland, and the UK. Trial occurred between 02 August 2022 and 25 June 2024.
Why was the research needed?
This study was performed to assess the efficacy to treat chorea and safety of SOM3355 compared to placebo in patients with HD.
What were the main questions studied?
The main question was to what extend chorea was decreased on treatment with SOM3355 compared to placebo and how safe was drug in HD patients compared to placebo.
Who participated in the study?
Adult men and women with a diagnosis of HD made by a movement disorders expert and with a Total Maximal Chorea (TMC) score of 10 or more were included in the study.
What treatments/interventions did the participants take/receive?
Capsules of SOM3355 or Placebo capsules with same appearance and weight but no active ingredient and no therapeutic benefit.
What medical problems (adverse reactions) did the participants have?
Treatment Emergent Adverse Events (undesired effects also called side effects emerging during the treatment)
Side effects are unwanted medical events that happen during the study and must be reported by the study participants.Not all patients in this trial had side effects: 79 of 139 patients had side effects (185 in total: 146 judged as mild, 37 moderate and only 1 severe), with 22 of 41 patients in the SOM3355 400 mg/day group reporting 47 side effects; 33 of 50 patients in the SOM3355 600 mg/day group reporting 90 side effects; and 24 of 48 patients in the placebo group reporting 48 side effects.
Out of the 185 side effects, 29 were considered as related to the study drug: 9 in the SOM3355 400 mg/day group, 15 in SOM3355 600 mg/day group and 5 in the placebo group.
10 patients total had to stop the study due to side effects, 6 of 50 patients in the SOM3355 600 mg/day treatment group, 1 of 41 patients in the SOM3355 400 mg/day treatment group, and 3 of 48 patients in the placebo treatment group.
Finally, 3 side effects were reported as serious by 3 patients, 1 subject in each treatment group, and all not related to the study drug.
What happened during the study?
Patients took orally two capsules per day (BID), i.e. one in the morning and one in the evening (every 12 hours) for at least 8 weeks from baseline to Visit 5 (maintenance treatment).
What were the results of the study?
The study showed significant improvements in chorea in those patients in the SOM3355 600 mg/day group not taking neuroleptics during the study, with the largest improvements in those patients not taking neuroleptics and with a baseline mean TMC score higher than 12 (value that corresponds to the upper mild range). The Clinical Global Impression of Change (CGI-C) showed a higher percentage of improved ("much improved" and "improved") patients for both treatment groups compared to the placebo with a stronger effect in the 600 mg/day group. Both SOM3355 groups reported greater symptomatic and motor improvements compared to placebo during the maintenance phase therapy. Overall, SOM3355 demonstrated efficacy in chorea control, especially at higher doses.
More than half of the patients experienced undesired (side) effects, all but one mild or moderate in severity, with a higher incidence in the SOM3355 600 mg/day group. Side effects led to study discontinuation in 10 patients. Serious side effects were only 3 and all considered as not related to the study drug.
There were limited reports of cardiological side effects: bradycardia (low heart rate) was reported in one case in the 400 mg/day group and 4 cases in the 600 mg/day group, syncope (fainting) occurred in one case in each treatment group, and one case of hypotension (low blood pressure) and 1 case of orthostatic hypotension (low blood pressure when one stands up) were reported in the 400 mg/day group. Depressive symptoms and sleepiness improved over time in the SOM3355 groups. There was no significant decline in cognitive function and akathisia (inability to sit or stay still) in all three treatment groups.
Conclusion: Based on the overall results of this study, SOM3355 600mg/day dose appeared to be efficacious to treat chorea, safe and well-tolerated in patients with HD.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
22/SC/0062
Date of REC Opinion
25 May 2022
REC opinion
Further Information Favourable Opinion