Date: 2016-04-13
Type of information: Completion of patient enrollment
phase: 2
Announcement: completion of patient enrollment
Company: Innate Immunotherapeutics (Australia)
Product: MIS416
Action
mechanism: immunomodulating agent/peptide. MIS416 is a biologically derived novel immune modulator. This muramyl dipeptide cross-linked into a microparticle targets myeloid cells. Research has now identified that myeloid derived innate immune cells can play a vital role in limiting inflammation and promoting myelin repair in CNS disorders including progressive multiple sclerosis. MIS416 targets these important myeloid derived innate cells. Analysis of blood samples from both animals and patients treated with MIS416 shows that MIS416 stimulates these cells to produce anti-inflammatory factors which are able to access the CNS. Analysis also shows that MIS416 treatment results in an increase in the number of the targeted cells. This is important because these cells are able to access the CNS and help clear myelin debris which also interferes with myelin repair. Finally, recent analysis of blood samples from patients who participated in the previous Phase 1B and 2A trials shows that MIS416 stimulates the production of neurotrophic factors.
Disease: secondary progressive multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country: Australia, New Zealand
Trial
details: The purpose of this phase 2b randomised, double-blind, placebo-controlled trial is to determine whether MIS416 administered once weekly over 12 months is safe, tolerable, and improves a range of signs and symptoms associated with secondary progressive multiple sclerosis. (NCT02228213)
Latest
news: * On April 13, 2016, Innate Immunotherapeutics announced the company has closed enrolment into the Phase * On October 7, 2014, Innate Immunotherapeutics provided an update regarding its Phase 2B trial for secondary progressive multiple sclerosis (SPMS). Following the August 2014 Ethics Committee approval allowing the West Australian Neuroscience Institute (WANRI) to initiate the Company’s trial of MIS416 in patients with SPMS, four patients have initially been screened and two consented to commence treatment. WANRI is now actively promoting the study and expects to recruit 30-40 patients into the study within the next six months. Innate’s second major site, Nucleus Network (adjacent to the Alfred Hospital in Melbourne) received Ethics Committee approval on September 10 and is now also actively recruiting patients. The site has reported significant early interest in the study. Thirteen patients have been initially assessed by the site’s medical staff. Of these, two will shortly undergo eligibility screening and six are currently reviewing the patient consent information. The site expects to enrol between 30 and 40 patients within the next four to six months. Sites in Brisbane and Adelaide are also applying for approvals to enable patients in those cities to also participate in the study.
2B placebo controlled efficacy trial of MIS416 in patients with secondary progressive multiple sclerosis (SPMS). The study has exceeded the original recruitment target of 90 subjects with the successful enrolment this week of the 93 rd patient. As part of gaining ethical approval to conduct the current efficacy trial in Australia, the company has undertaken to make MIS416 available to patients completing the 12-month study. To date nine of the 13 patients who have completed the study have requested support from their physicians to enable access to MIS416 post-study.
The study will be completed this time next year with a substantive initial report expected about four months later.
Innate Immunotherapeutics also reported strong ongoing interest in the study from several major pharmaceutical
companies. They had multiple meetings prior to the commencement of the current Phase 2B trial in late 2014 with the study design benefitting as a result of these discussions. Subsequently Pharma have sought regular updates on the progress of the study as well as the ongoing scientific work into the novel mechanism of action of MIS416.
* On December 12, 2014, Innate Immunotherapeutics announced that the company has agreed to supply its drug candidate for secondary progressive multiple sclerosis to a small number of additional patients on compassionate grounds. The patients all live in Auckland, New Zealand, and as such are not able to enrol into the
Company's Australian based Phase 2B efficacy trial of MIS416 in patients with SPMS. The patients are all long time sufferers of multiple sclerosis and having initially endured the relapsing-remitting phase of the disease, where there are a number of approved therapies, they now face the prospect of steadily increasing disability and no approved effective drugs. Innate Immunotherapeutics' drug MIS416 has previously demonstrated a favourable safety and tolerability profile and in an early stage Phase 2A trial, 80% of the patients recorded a 20% or better
improvement in their multiple sclerosis related clinical status.
The seven new 'compassionate use' patients who have recently started receiving MIS416 in Auckland join a group of 18 SPMS patients who have been administered MIS416 by their doctors for periods ranging from 15 months to over six years. Of these 18 patients, 15 (or 83%) have selfreported significant and sustained improvements in many of the disabilities associated with SPMS. A sub group of these existing compassionate use patients, comprising nine patients who participated in the Company's previous New Zealand based Phase 1B and 2A trials, have been regularly completing the Short Form - 36 question health survey questionnaire (SF-36). The SF-36 is a patient reported outcome measurement widely used to obtain the patient's perspective on the effects of their treatment. In the most recent analysis of these SF-36 results, 8 patients showed improvements that met or exceeded the "clinically significant threshold" in at least three areas of disability. These results are very consistent with the results from earlier survey time points. In addition to regularly completing the SF-36 survey, the new compassionate use patients will also be monitored using several of the neuro-muscular measurements being used in the Australian based Phase 2B trial. The first results from these regular assessments are expected to be available in April or May next year and quarterly thereafter.
* On November 11, 2014, Innate Immunotherapeutics provided an update regarding its Phase 2B trial for secondary progressive multiple sclerosis. Patient dosing with MIS416 is now underway at the West Australian Neuroscience Institute (WANRI) in Perth and at Nucleus Network's AMREP Centre for Clinical Studies in Melbourne. Each site has dosed their first two patients with several more patients due to commence treatment this month. A Brisbane site, the Wesley-St. Andrew’s Research Institute (WSARI), will be initiated on November 12th and will start recruiting patients shortly thereafter.
During September 10 to 13, Innate’s Chief Scientific Officer Dr Gill Webster presented data from the Company’s previous Phase 2A trial to delegates at the MS Boston 2014 conference, a joint meeting of ACTRIMS and ECTRIMS (the America’s Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis). These data were obtained by analysing blood samples from patients who received weekly doses of MIS416 over a three month period as part of the Company’s previous Phase 2A trial. The results showed that MIS416 treatment increased anti-inflammatory proteins which might regulate inflammation inside the brain of SPMS patients.
Following requests from several New Zealand based patients and their doctors, Innate has agreed to the further supply of MIS416 on compassionate grounds. The decision takes into account that there are no current plans to extend the Phase 2B trial to NZ and therefore accessing MIS416 as a trial participant is not an option for these patients. The approximately twelve new compassionate patients have agreed to have their MS related signs and symptoms monitored every three months in Auckland using a number of assessments also being used in the Phase 2B trial currently underway in Australia. Four of these patients had baseline assessments recorded on September 29th and another four will have these assessments carried out on October 14th. The remaining four so patients will be assessed at the end of October.
