A Phase 1b study on SPL026 with or without SSRIs in participants with MDD
Research type
Research Study
Full title
An Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic and Exploratory Efficacy of Intravenous Dosing of SPL026 (DMT Fumarate [A Serotonergic Psychedelic]) Alone or in Combination with Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder
IRAS ID
1005892
Contact name
Victoria Attwooll
Contact email
Sponsor organisation
Small Pharma Ltd
Eudract number
2022-001767-27
Clinicaltrials.gov Identifier
Research summary
Research Summary
This is a study of SPL026 (the study medicine) – a psychedelic substance that occurs naturally in plants and animals.
We’re testing SPL026 and therapy as an experimental treatment for Major Depressive Disorder (MDD). MDD, or ‘depression’, is a common mental illness that affects about 280 million people worldwide. There are existing treatments for depression, but they don’t work well in all patients.
SPL026 acts at sites in the brain (called serotonin receptors) related to mood and mental health. We hope SPL026 will give patients with depression more treatment options.
We’ll test single doses of SPL026 (given by slow injection into a vein) to assess: its safety; how well it’s tolerated; its blood levels; psychedelic effects; and effects on mood, feelings, thoughts and beliefs.
We’ll give up to 24 participants a single dose of SPL026. Of these, up to 18 will be currently taking medication (called a selective serotonin reuptake inhibitor or SSRI) for their depression but for whom the SSRI is not fully relieving their depression. Six participants will not be currently taking any medicinal treatment for their depression. Participants will take up to 17 weeks to finish the study. They’ll stay at the clinical research units for 2 nights/3 days and have 3 follow-up video calls.
Potential participants, who have consented to take part in the call, will have a pre-screening video call to assess their suitability for the study and if suitable will attend a screening visit up to 17 weeks before the study depending on the length of screening (3 month window).
A pharmaceutical company (Small Pharma, UK) is funding the study.
The study will take place at 2 centres in the UK.
Summary of Results
The study was organised and funded by Small Pharma Ltd (the ‘Sponsor’) and was run by MAC Clinical Research at 2 clinics in the UK from November 2022 to August 2023.
Why was this study conducted?
The purpose of this study was to test a drug called SPL026 (study drug) that is being developed to treat depression, also known as major depressive disorder.
Depression is a common mental health illness. In the UK around 1 in 4 people experience depression at some stage in their life. Depression affects people in different ways and causes a wide range of symptoms. These include feelings of unhappiness and hopelessness, feelings of guilt or low self-worth, anxiety, low energy, loss of interest or pleasure, poor concentration, and disturbed sleep.
There are a number of medicines available to treat depression, but for around 1 in 3 people, they do not work properly or cause unpleasant side effects resulting in people not taking them.
It is hoped that this study drug may lead to new treatments for people with depression. The study drug contains DMT (N, N-dimethyltryptamine) a psychedelic or mood-altering chemical found naturally in many plants and animals. DMT is the main ingredient in ayahuasca, a hallucinogenic drink used for centuries in religious ceremonies in some South American countries. Substances like DMT act on the brain, causing temporary changes in awareness, sensation, and emotions.
The aims of the study were to assess:
• how safe and tolerable the study drug is
• how the body absorbs and removes the study drug
• how effective the study drug is in improving depression symptoms.
All participants were informed that they would receive the active study drug at the same dose (27.5 mg). The study drug was given once as an injection.
Who took part in the study?
Altogether, 19 participants with depression were in this study, of whom 1 participant left before receiving the study drug and 1 participant stopped the injection before having the full dose. Participants were divided into 2 groups; Group 1 were taking an antidepressant (any type of selective serotonin reuptake inhibitor or SSRI) that did not fully relieve their depression symptoms, and Group 2 were not taking any antidepressants for at least 6 weeks before the study.
What happened during the study?
In the course of this study, participants came to the clinic up to 5 times. During the first visit participants underwent a range of health checks and filled in questionnaires to confirm that the study was safe for them to take part in. The second visit included 2 overnight stays. Participants checked into the clinic 1 day before they took the study drug and then stayed for an additional night to fill in depression questionnaires and for additional health checks. After being discharged from the clinic participants came for 3 follow-up visits either in-person or via video-call to fill in depression and anxiety questionnaires and for additional health checks. The maximum length of participation in this study was approximately 17 weeks.
What were the overall results of the study?
Some participants reported side effects but none of these were serious or a safety concern. In this study, nausea and vomiting were the most often reported side effects. These were experienced by 2 participants and thought to be probably or possibly due to the study drug. All participants responded ‘No’ to the question (‘Do you wish you had not gone through that experience?’) suggesting that the study drug was well tolerated.
Depression symptoms were measured with 2 questionnaires and anxiety symptoms were measured with 1 questionnaire. The answers showed that the study drug reduced depression and anxiety symptoms in both groups. The results also suggest that the improvement in depression and anxiety symptoms after one dose of the study drug continued for up to 4 weeks. Interestingly, the results showed that Group 1 benefitted slightly more as their depression and anxiety symptoms seemed to be lower compared to Group 2. This finding needs to be taken with caution as larger studies are needed to confirm the result.
How has this study helped people with depression and researchers?
This study was in women and men aged 18 or older diagnosed with depression but who were otherwise healthy. The results apply to the particular people studied and may not be true for everybody. Not all participants in the study had the same results.
This research helps us to understand more about the medicine being studied. The results will be used in other studies to compare this drug with other treatments for depression.
Are there any plans for further studies?
No further studies are planned with the study drug. However, the Sponsor will use information learnt from this study for their research into other similar drugs.
Where can I find more information about this study?
To learn more about this study, visit: https://clinicaltrials.gov/study/NCT05553691 and https://www.isrctn.com/ISRCTN10974027.
This summary was written on 05 June 2024 and includes only results from one study. Other studies may find different results and newer information may exist.REC name
London - Brent Research Ethics Committee
REC reference
22/LO/0431
Date of REC Opinion
11 Aug 2022
REC opinion
Further Information Favourable Opinion