PrevANZ Vitamin D MS Prevention Trial
Progress Report
March 2013
Background
PrevANZ is a world-first clinical trial that will test whether vitamin D supplementation can prevent MS in those at risk of developing the disease.
It is a Phase IIbrandomised, double blind, placebo-controlled trial that will test the safety and efficacy oforal vitamin D supplementation to prevent a diagnosis of MS following a person’s presentation with a first episode of symptoms (CIS or clinically isolated syndrome).
Eligible CIS patients will be enrolled over the course of the next three years and will be randomised to receive doses of 1000I.U., 5000 I.U., and 10,000 I.U. vitamin D3 or placebo for 48 weeks. Patients will be monitored by clinical and MRI measures to determine if oral vitamin D supplementation can delay or prevent a second clinical or radiological event.
Progress update
Steering Committee and logistical management
Over the second half of 2012 MSRA has worked with the PrevANZ Steering Committee and the not-for-profit contract research organisation, Neuroscience Trials Australia (NTA),to make all the necessary preparations to commence the trial. In the first quarter of 2013, the final logistical arrangements are now being made in preparation for site initiation. In this final active phase prior to site initiation the Steering Committee are conducting monthly teleconferences. A smaller working group meets with NTA and MSRA project manager, Dr Lisa Melton, every fortnight to monitor progress and discuss items arising.
Trial sites
20highly experience MS trial sites (15 in Australia, 5 in New Zealand) have committed to conduct the trial. All sites have ethics approvals in place. One further site may join later in 2013.
Site budgets have been finalised, with all sites having worked hard to keep their site and per patient costs as low as possible to assist this non-commercial, investigator-initiated trial.
Clinical Trial Research Agreements have now been drawn up for all sites for final regulatory approval by the sites and the sponsor (MSRA).
Central MRI reading centre
The Central MRI Reading team at the Institute of Neurology,University College London, UK, have supplied necessary protocol details to the PrevANZ team for capture and transfer of MRI scans for reading.The UK team are playing a close collaborative role with thePrevANZ team and are actively discussing potential funding sources for this UK-based component of the trial.
Vitamin D capsules
Lipa Pharmaceuticals has now delivered the vitamin D and placebo capsules to the central pharmacy at the Austin Hospital, Melbourne. The Austin pharmacy have been working with NTA on logistical arrangements for randomisation and shipping of the study drug. The randomisation arrangements ensure that all sites will administer a balanced distribution of doses and placebo – double-blinded to the patient and the clinical team – this will help to mitigate againstthe factors of latitude and UV exposure for patients at different trial sites,that may confound the results.
The capsules have a two year expiry and a second batch will be ordered as required, approximately half-way through the trial. As standard practice, a sample of capsules has been sent to the independent stability testing company, Chemical Analysis, to confirm the stability of the vitamin D3 doses at regular time points across the two year period. Testing of the first sample of capsules at this time point confirms vitamin D stability and doses are within the correct range.
Logistics
The Protocol, Patient questionnaires and Patient Informed Consent Formswere finalised in December 2012. The electronic clinical research form (eCRF) for data capture has been completedand is now undergoing final testing by study coordinators and lead investigators at the sites. The laboratory and study manuals for investigatorsat the PrevANZsites are close to finalisation.
Site initiation and enrolment
Now that budgets, manuals, eCRF and, most importantly,Clinical Trial Research Agreements are very close to completion, NTA is now booking appointments to conduct site initiation visits with all trial investigators. As soon as site initiation has taken place the investigators can commence screening and enrolling eligible patients. Hence we now anticipate that the first patients will be enrolled in April.
Funding update
The Trial budget currently remains at $2.6 million dollars, consisting of contributions from Foundation 5Million+, Trish MS Research Foundation, the John T Reid Charitable Trusts, MS Societies of WA, Tasmania and Queensland, Clayton Utz Foundation and other private donors. This will allow a statistically valid cohort of approximately 180 patients. MSRA and the PrevANZ steering committee continue their efforts to raise a further $1 million to achieve a fully enrolled trial of 240 patients for a statistically robust and conclusive result to the trial. This includes investigation of possible government (NHMRC) funding schemes.
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