Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05237544 |
| Other study ID # |
18NM20 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 11, 2019 |
| Est. completion date |
March 30, 2021 |
Study information
| Verified date |
February 2022 |
| Source |
Great Ormond Street Hospital for Children NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Spinal muscular atrophy (SMA) is a motor neuron disorder caused by the absence of a
functional survival of motor neuron 1, telomeric (SMN1) gene. Type I SMA, a lethal disease of
infancy, accounts for the majority of cases. Newborn blood spot screening (NBS)to detect SMA
has been implemented in public health laboratories in some countries already. In the UK dried
blood spots are collected within a few days of birth on all babies and subsequent newborn
screening is currently carried out for other diseases but not for SMA. The investigators
would like to carry out a proof of principal testing to show that an assay for SMA can be
carried out on these routinely collected dried blood spots (completely anonymised). The
investigators would also run some known anonymised SMA positive dried blood spots. The aim is
to demonstrate that a simple robust test can be used in a routine diagnostic laboratory to
accurately screen for SMA. The investigators will not have access to identifiable data or
samples for this project.
Description:
Spinal muscular atrophy (SMA) is a motor neuron disorder caused by the absence of a
functional survival of motor neuron 1, telomeric (SMN1) gene. Type I SMA, a lethal disease of
infancy, accounts for the majority of cases. The majority of babies born with SMA become
symptomatic as babies (type I) or as toddlers (type II). Type I children will never sit
unsupported, require ventilated support in the first year of life and usually die before 2
years of age. Type II children can survive to early adulthood but will never walk. They
almost invariably develop severe curvature of the spine, feeding and respiratory
insufficiency that require appropriate intervention. Cognitive abilities are not impaired and
children are generally bright and sociable.
Several new therapies have recently been developed for children with SMA and have shown
remarkable success in clinical trials. One of these therapies, spinraza, has received both
FDA and EMA approval and is commercially available in most EU countries and in the US, and is
being currently evaluated by NICE. Because of the early onset and rapid progression of
infantile SMA, prompt detection of the disease is essential to enable successful treatment.
It is now recommended that infants be screened for SMA, enabling early drug treatment thus
preventing further neuron damage2. The recently published work on the development of spinraza
indeed supports the view that children with shorter disease duration had much better outcome
[the 2 NEJM papers] a concept that is also emphasised by the interim analysis of infants who
received spinraza presymptomatically as part of an ongoing study sponsored by Biogen (Nurture
study). The majority of these children had met the age appropriate milestones by the age of 1
year, a clearly remarkable outcome. Similar very promising results were obtained in a
recently published AAV gene therapy study in which a number of the severe infants affected by
type 1 SMA achieved even the ability to walk unsupported (Mendell SMA gene therapy NEJM
2017). Also in this manuscript, the children who had a shorter disease duration and those
treated shortly after the diagnosis had a much better outcome compared to children treated
later. While the findings from this early gene therapy study are currently being extended in
a larger global phase 3 study, these dramatic results from emerging therapies have led many
countries to include SMA in their respective newborn screening programmes.
A previous study (Adams et al. 2014, J. Clin. Imm) was carried out in an almost identical way
to the study planned here. The previous study utilised 5000 anonymised leftover blood spots
from a routine NBS lab to test the robustness and practicality of running a NBS assay for
SCID. This study was scientifically critiqued leading to publication in a respected relevant
scientific journal. The study planned here is identical in the approach (5000 normal leftover
blood spots) to test the robustness and practicality of using a commercial assay for NBS for
SMA in a routine clinical lab environment. As in the previous SCID study we plan to use a
number of retrospective known positive samples as well as all the necessary positive/negative
controls contained in the commercial kit. The sole aim of the study is to assess the
performance of the commercial kit to provide evidence that NBS screening for SMA could
feasibly be carried out in routine NBS screening labs.
The investigators therefore believe this is the correct route to take with SMA Newborn
Screening as well. Assays for detection of SMA using the dried blood spots collected for
Newborn Screening (NBS) have now been developed. This utilises the amplification of the SMN1
gene and subsequent detection of the deleted section that causes SMA. Newborn blood spot
screening to detect SMA has been implemented in public health laboratories in some countries
already. In the UK, dried blood spots are collected within a few days of birth on all babies
and subsequent newborn screening is currently carried out for other diseases but not for SMA.
The investigators would like to carry out a proof of principal testing to show that an assay
for SMA can be carried out on these anonymised routinely collected dried blood spots. We
would also run some known anonymised SMA positive dried blood spots. The aim is to
demonstrate that a simple robust test can be used in a routine diagnostic laboratory to
accurately screen for SMA.
