Today, 28th February, is Rare Disease Day. On a fitting day for our rare disease community, we can announce that the UK Regulatory Agency (MHRA) has given approval for the tamoxifen clinical trial, known as ‘TAM4MTM’, to begin for child patients with x-linked myotubular myopathy in the UK.
TAM4MTM is a drug repurposing trial, testing the effect of the drug tamoxifen on muscle and respiratory strength in patients with x-linked myotubular myopathy. Safety and tolerability will also be carefully monitored, with gaps of four weeks between each participant beginning on the trial.
The UK arm of the trial will enrol child patients, aged 2 – 18 years. This is a multi-centre trial which, as well as in the UK, will also be active in three other clinical sites in Canada and USA and involve 16 participants in total. The first patients already began to receive tamoxifen in Canada, in 2021. The study in the UK will be led by Dr Giovanni Baranello and Professor Francesco Muntoni at Great Ormond Street Hospital for Children (GOSH) and the UCL Great Ormond Street Institute of Child Health in London.
All participants will receive tamoxifen (ApoTamox) for approximately 6 months. Participants will either begin on tamoxifen, or on a placebo (an inactive pill). After 6 months, there will be a ‘wash-out’ period of 3 months in order to flush the tamoxifen or the placebo out of the system, and then the participants will cross-over to the other treatment (either tamoxifen or placebo) for 6 months. This is a ‘double-blind’ study, which means neither the participant nor the study doctors will know which pill the participant is taking (tamoxifen, or placebo).
How do I find out more about this trial?
To register interest in participating, you can email clinicaltrials.neuromuscular@gosh.nhs.uk. You can also read more about how participants are selected in this letter from Great Ormond Street Hospital (GOSH). We will update you with more information as we receive it from the team at GOSH.
What is a repurposing trial?
A repurposing trial is when known drugs or compounds that are already licensed for use in other conditions, are tested in different conditions, for which they have not yet been licensed. However, as the drugs are already known and taken by many other people, repurposing trials are easier to run, and it is often quicker to get a license once the drug is proven effective.
Tamoxifen also has the benefit of having low side effects in both adults and children. It is widely available, not costly and is already being taken safely by children for a range of other conditions.
If this study is successful, it could provide the first widely available therapy for x-linked myotubular myopathy, either as a stand-alone treatment for patients not eligible for other treatments that emerge, or as a valuable additional treatment.
How was the potential therapeutic effect of tamoxifen discovered?
In earlier work, funded by Myotubular Trust grants (2014-16), there was an incidental, unexpected finding that tamoxifen – the well known breast cancer drug – could significantly improve the symptoms associated with x-linked myotubular myopathy.
The Myotubular Trust subsequently funded a three year grant (2018-2021) with the same team to expand their study of tamoxifen – how it worked in x-linked myotubular myopathy, and what dosages to use – which led to the inception of these trials.
‘This work ultimately has led to a clinical trial of tamoxifen for XLMTM,which launched earlier in 2021’ Dr Jim Dowling, Sick Kids, Canada.
Who pays for the trial if there is no company involved?
The UK arm of this TAM4MTM trial is being jointly funded by the Myotubular Trust and the charity arm of the world-renowned Great Ormond Street Hospital (GOSH). You can read more about the collaborative efforts here between our two charities.
Glossary
Placebo – is an inactive drug or pill which has no therapeutic effect and is used as a ‘control’ in trials
Wash-out – a pre-defined period of time before or during a clinical trial when participants receive no active medication
Double-blind – a patient and their treating clinician is unaware of which drug is being used (drug or placebo) due any information influencing the behaviour of the tester or the participant
MHRA – The Medicines and Healthcare products Regulatory Agency is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptably safe.
