25891548
BACKGROUND	Infusion of PDA-001 , a preparation of mesenchymal-like cells derived from full-term human placenta , is a new approach in the treatment of patients with multiple sclerosis .
OBJECTIVE	This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis .
METHODS	This was a phase 1b , multicenter , randomized , double-blind , placebo-controlled , 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis .
METHODS	The study was conducted at 6 sites in the United States and 2 sites in Canada .
METHODS	Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 ( 15010 ( 6 ) cells ) or placebo , given 1 week apart .
METHODS	After completing this cohort , subsequent patients received high-dose PDA-001 ( 60010 ( 6 ) cells ) or placebo .
METHODS	Monthly brain magnetic resonance imaging scans were performed .
METHODS	The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity .
METHODS	This was monitored using Cutters rule ( 5 new gadolinium lesions on 2 consecutive scans ) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse .
RESULTS	Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment : 6 to low-dose PDA-001 , 6 to high-dose PDA-001 , and 4 to placebo .
RESULTS	No patient met Cutters rule .
RESULTS	One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001 .
RESULTS	No other patient had an increase in Expanded Disability Status Scale score > 0.5 , and most had stable or decreasing Expanded Disability Status Scale scores .
RESULTS	With high-dose PDA-001 , 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis .
RESULTS	Other adverse events were mild to moderate and included headache , fatigue , infusion site reactions , and urinary tract infection .
CONCLUSIONS	PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis patients .
CONCLUSIONS	No paradoxical worsening of lesion counts was noted with either dose .

