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Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9;2(3):e100. doi: 10.1212/NXI.0000000000000100. eCollection 2015 Jun.

Randomized phase 2 trial of NP001-a novel immune regulator: Safety and early efficacy in ALS.

Collaborators (135)

Katz J, Kushner G, Wong C, Engel M, Forshew D, Osborne R, Schug B, Akers A, Brent B, Zayas-Bazan T, McCoy S, Goyal N, Harris W, Gonella M, Brooks BR, Bravver E, Sanjak M, Ward AL, Mehrizi A, Belfiore M, Larry C, Nemeth J, Conway J, Bender R, Holsten S, Shue J, Mitsumoto H, Youngman R, Armstrong N, Lee YW, Weimer LH, Brannagan T 3rd, Hirano M, Scotto M, Dalton K, Bedlack RS, Morgenlander JC, Boyette CL, Grace KL, Arvik BM, Thomas Hickey P, Lasater Scott B, Lynn Heydt D, Perry-Trice P, Cudkowicz M, Berry J, Atassi N, Boylan K, Kennelly K, DeSaro P, Johnston A, Huser A, Fuqua P, Staggs K, Babcock L, Kryston T, Ross MA, Bosch EP, Verheijde JL, Grover Y, Duffy AK, Lee MS, McLaughlin RR, Musil DJ, Early J, Whiteman D, Wisbey JA, Simpson EP, Pleitez MY, Lay LF Jr, Halton SL, Schwartz T, Blanton L, Lai EC, Pioro EP, Kuenzler R, Berry N, Khan S, Chowdhury N, Biernot J, Goslin K, Carter GT, Corkrey PM, Kovarik MA, Shefner JM, Simionescu L, Grosso M, Watson ML, Reale MA, Duleep A, Carhart R, Markis K, Money K, Boevin T, Lava N, Glass JD, Polak M, Shaw L, Bordeau J, Rogers S, Ferguson S, Fournier C, Kelly C, Mozaffar T, Wang AK, Ramsey G, Tully PA, Graves M, Wiedau-Pazos M, Alvarez R, Barohn R, McVey AL, Dimachkie MM, Pasnoor M, Herbelin L, Walsh M, Kasarskis EJ, Dotson WF, Sitzlar SC, Tandy T, Carrico J, Phillips S, Rice L, Holbrook KM, Eckmann D, Chamblin L, Townsend J, Kaenzig J, Hanley-Borgia L, Vanderpool KE, Taylor DG, Carpenter J, Thomas S, Hutchinson J, King JT.

Author information

California Pacific Medical Center (R.G.M., J.S.K.), San Francisco, CA; Neuraltus Pharmaceuticals, Inc. (G.B., V.G., M.S.M., A.A.), Palo Alto, CA; University of Kansas (R.J.B.), Kansas City; Massachusetts General Hospital (M.C.), Boston; University of California, San Francisco (R.Z., M.S.M.); Agility Clinical, Inc. (E.L.), Carlsbad, CA; and The Methodist Hospital (S.H.A.), Houston, TX.



To assess the safety, tolerability, and preliminary efficacy of NP001, a novel immune regulator of inflammatory monocytes/macrophages, for slowing progression of amyotrophic lateral sclerosis (ALS).


This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of <3 years' duration and forced vital capacity ≥70%. Participants received NP001 2 mg/kg, NP001 1 mg/kg, or placebo for 6 months. Safety, tolerability, and inflammatory biomarkers were assessed throughout the study. Preliminary efficacy was evaluated using the ALS Functional Rating Scale-Revised (ALSFRS-R) slope and change from baseline, with and without matched historical placebo controls, after 6 months of treatment. A post hoc analysis of the percentage of patients ("responders") whose ALSFRS-R did not change from baseline was also conducted.


NP001 was generally safe and well-tolerated, except for infusion site pain and dizziness. No significant slowing of decline in the primary or secondary measures was observed. However, slowing of progression was observed in the high-dose group in patients with greater inflammation (wide range C-reactive protein). Moreover, NP001 may have dose dependently halted symptom progression in a subset of patients. More than 2 times as many patients on high-dose NP001 (25%) did not progress during 6 months of treatment compared with those on placebo (11%). Most "responders" had an elevated biomarker of inflammation, interleukin-18, and were positive for lipopolysaccharide at baseline, which decreased after treatment with NP001.


The arresting of progression of ALS symptoms by NP001 in a subset of patients with marked neuroinflammation, as observed here, will represent a novel therapeutic approach for patients with ALS, if confirmed.


This study provides Class I evidence that for patients with ALS, NP001 is safe and did not significantly slow progression of the disease (difference in slope of the ALSFRS-R/month 0.12 favoring NP001, p = 0.55). The study lacks the precision to exclude an important effect of NP001.

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