SPRINT-MS (NN102) "A randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and activity of ibudilast (MN-166) in subjects with progressive multiple sclerosis"

Study ID
STU 042013-043

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

Contact
William Thayer
214-648-2926
william.thayer@utsouthwestern.edu

Principal Investigator
Angela Flores

Summary

Despite recent improvements in pharmacotherapy for relapsing remitting multiple sclerosis (RRMS),
there are no therapies with demonstrated efficacy in progressive multiple sclerosis (MS) in the absence
of relapses. The few studies showing efficacy of anti-inflammatory therapies in progressive forms of
MS were likely driven by the anti-inflammatory effect of the therapies. There is great need for a safe,
effective, and conveniently-administered therapy for progressive MS without overt inflammation.
Ibudilast (MN-166, aka AV411) is a small molecule macrophage migration inhibitory factor (MIF)-
and phosphodiesterase (PDE)-4, 10-inhibitor drug candidate with demonstrated neuroprotective action
in vitro and in vivo. MIF knockout or antibody-neutralization studies have provided neuroprotection
validation in certain MS and other neurological animal models. Ibudilast has additionally shown
attenuation of glial cell activation in multiple in vitro and in vivo model systems. Hence, these
molecular and cellular actions by ibudilast represent a novel pharmacotherapy approach which may
provide unmet needs in progressive MS.

Participant Eligibility


* Written informed consent is obtained and willing and able to comply with the protocol in the
opinion of the Investigator.

* Male or female subjects ages 21 to 65, inclusive

* Confirmed diagnosis of SPMS or primary progressive multiple sclerosis (PPMS) according to
2010 International Panel Criteria

* Typical MS lesions on brain MRI according to Swanton[?]s MRI Criteria

* EDSS 3.0-6.5, inclusive

* Clinical evidence of disability progression in the preceding two years, as measured by any of
the following (excluding progression during clinical relapses):
o worsening overall EDSS of at least 0.5 points (may be assessed retrospectively) or
o 20% worsening in 25-foot walk (25-FW) or
o 20% worsening in 9-hole peg test (9-HPT) in either hand

* Existing multiple sclerosis pharmacotherapy status may include interferon-beta or glatiramer
acetate or none (i.e. untreated).

* Females of child-bearing potential must have a negative serum [lower beta]-hCG at screening and must be
willing to use appropriate contraception (as defined by the investigator) for the duration of
study treatment and 30 days after the last dose of study treatment.

* Males should practice contraception as follows: condom use and contraception by female
partner.

* Subject is in good physical health on the basis of medical history, physical examination, and
laboratory screening, as defined by the investigator.

* Subject is willing and able to comply with the protocol assessments and visits, in the opinion of
the study nurse/coordinator and the Investigator.