Autologous Haematopoietic Stem Cell Transplantation for highly active treatment resistant multiple sclerosis.

Phase 2

Recruiting

• Conditions: Relapsing Remitting Multiple Sclerosis; Neurological - Multiple sclerosis; Inflammatory and Immune System - Autoimmune diseases

• Registration Number: ACTRN12619000348156
• Lead Sponsor: Alfred Health

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-06
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1.Male and female participants aged 18-60 with MS (2017 revised McDonald criteria)
2.Expanded Disability Status Scale (EDSS) score between 0 and 6
3.Highly active RRMS despite continuing to use conventional treatment for RRMS within the past 2 years.
Definition of ‘highly active’ RRMS
i.
1.Greater than or equal to 1 severe relapses (Change in EDSS greater than or equal to 1 or 0.5 for those with pre relapse EDSS greater than or equal to 5.5) (or documented changes in neurological examination consistent with these magnitudes) and/or incomplete recovery from clinically significant relapses within the last 12 months
and
2.Greater than or equal to 1 gadolinium-positive (Gd+) lesion of diameter greater than or equal to 3 mm on MRI within the past 6 months.
or
3.Accumulation of any new T2 lesions on follow up MRI scans

ii.
1.Change in EDSS greater than or equal to 1 or 0.5 for those with pre relapse EDSS greater than or equal to 5.5)
and
2.evidence of new MRI activity either T1 or T2 performed on follow up MRI scans
4.Neurologically stable participants with no evidence of relapse for at least 30 days prior to study entry into the treatment period.
5.Females of childbearing potential must
a. have a negative pregnancy test at baseline prior to entry into the treatment period
b. use simultaneously two forms of effective contraception (either i.e partner) during and for 3 months after HSCT
c. females that are either post-menopausal for 12 months prior to entry into the treatment period or surgically sterile (through hysterectomy or bilateral oophorectomy) are not required to use birth control.
6. Able to provide informed consent and the absence of mental and cognitive deficits which can interfere with the capability of providing the informed consent for participation in the study prior to the Screening.

Exclusion Criteria

1.Participants with a non-relapsing form of MS (primary or secondary progressive MS)
2.Participants with any medically unstable condition, as assessed by the primary treating physician.
3.Participants with any of the following cardiovascular conditions:
a)history of cardiac arrest;
b)myocardial infarction within the past 6 months prior to enrolment or with current
unstable ischemic heart disease
c)cardiac failure at time of Screening (Class III, according to New York Heart
Association Classification) or any severe cardiac disease as determined by the
investigator.
d)Left Ventricular (LV) ejection fraction < 45%
e)hypertension, not controlled by prescribed medications
4.Participants with any of the following pulmonary conditions:
a)severe respiratory disease or pulmonary fibrosis;
b)tuberculosis, except for history of successfully treated tuberculosis or history of
prophylactic treatment after positive PPD skin reaction
c)abnormal chest x-ray suggestive of active pulmonary disease;
d)abnormal Pulmonary Function Tests: FEV1, FVC values lower than 70% of
predicted, DLCO values lower than 60% of predicted.
5.Participants with any of the following hepatic conditions
a)known history of alcohol abuse, chronic liver or biliary disease
b)total bilirubin greater than the upper limit of the normal range, unless in context of
Gilbert’s syndrome
c)conjugated bilirubin greater than the upper limit of the normal range
d)AST, ALT greater than 2 times the upper limit of the normal range
e)alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal
range;
f) gamma-glytamyl-transferase (GGT) greater than 3 times the upper limit of the normal
range
6. Participants with abnormal laboratory values
a)serum creatinine >150 µmol/L.
b)white blood cell (WBC) count <3.5x109/L or lymphocyte count <0.8x109/L
7.Participants with any of the following neurological or psychiatric conditions
a)history of substance abuse (drug or alcohol) or any other factor (i.e., serious
psychiatric condition) that may interfere with the subject’s ability to cooperate and
comply with the study procedures
b)progressive neurological disorder, other than MS, which may affect participation in
the study or require the use of medications not allowed by the protocol.
8.Participants unable to undergo MRI scans, including history of severe hypersensitivity
to gadolinium
9.Participation in any clinical research study evaluating another investigational drug or
therapy within 6 months prior to baseline.
10.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and
11.Participants unwilling to use effective contraception

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective of the cohort study is to assess the safety, as measured by transplant related mortality at Day 100 (defined as death in the first 100 days not due to MS)[Day 100 post transplant];To assess the efficacy of HSCT as measured by (a) mean time to first relapse (clinical and MRI), (b) mean time to 3 and 6 month sustained change in EDSS and (c) mean annualised relapse rate in participants with multiple sclerosis refractory to standard therapies. [Month 60]

Secondary Outcome Measures

Name	Time	Method
To assess tolerability of the autograft between d100 and d365, particularly with respect to infectious sequelae. This will be assessed by monitoring the occurrence of infectious sequelae as adverse events[Day 365 post transplant]