Randomized phase 2 trial of NP001–a novel immune regulator: Safety and early efficacy in ALS
OBJECTIVE: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). METHODS:This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 1...
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| Veröffentlicht in: | Neurology : neuroimmunology & neuroinflammation 2015-06, Vol.2 (3), p.e100-e100 |
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| creator | Miller, Robert G Block, Gilbert Barohn, Richard J Cudkowicz, Merit Zhang, Jane R McGrath, Michael S Appel, Stan H Katz, Jonathan Kushner, Giovanna Wong, Cynthia Akers, Amy Zayas-Bazan, Thais McCoy, Shelly Goyal, Neelam Harris, Will Gonella, Marie Brooks, Benjamin R Bravver, Elena Sanjak, Mohammed Ward, Amber L Mehrizi, Amir Belfiore, Mark Lary, Cynthia Nemeth, Joanne Conway, Jill Holsten, Scott Shue, Jamie Mitsumoto, Hiroshi Youngman, Regina Lee, Yei-won Dalton, Kate Bedlack, Richard S Morgenlander, Joel Charles Boyette, Candace Lee Grace, Karen L Thomas Hickey, Patrick Perry-Trice, Peggy Berry, James Atassi, Nazem Boylan, Kevin Kennelly, Kathleen DeSaro, Pamela Johnston, Amelia Huser, Angela Fuqua, Paula Staggs, Kristin Babcock, Lorraine Kryston, Thomas Bosch, E Peter Verheijde, Josephus L Grover, Yvvonne Lee, Michael S Musil, Danette J Whiteman, Dana Simpson, Ericka P Pleitez, Milvia Y Lay, Luis F Schwartz, Thomas Blanton, Linda Lai, Eugene C Berry, Nicole Khan, Sara Chowdhury, Nabi Goslin, Kimberly Carter, Gregory T Ann Kovarik, Mary Simionescu, Laura Reale, Melissa A Markis, Katie Money, Kristina Boevin, Travis Lava, Neil Glass, Jonathan D Polak, Meraida Shaw, Latoya Bordeau, Jane Rogers, Susan Ferguson, Susan Kelly, Crystal Mozaffar, Tahseen Ramsey, Gladys Tully, Patricia A Alvarez, Rebecca Barohn, Richard Dimachkie, Mazen M Pasnoor, Mamatha Herbelin, Laura Kasarskis, Edward J Dotson, William F Sitzlar, Stephen C Tandy, Tammy Carrico, Jeffery Rice, Linda Chamblin, Lisa Townsend, Janet Hanley-Borgia, Lisa Vanderpool, Kathryn E Taylor, Deborah G Hutchinson, Jan King, Jason T |
| description | OBJECTIVE: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).
METHODS:This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of |
| doi_str_mv | 10.1212/NXI.0000000000000100 |
| format | Article |
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Block, Gilbert ; Barohn, Richard J ; Cudkowicz, Merit ; Zhang, Jane R ; McGrath, Michael S ; Appel, Stan H ; Katz, Jonathan ; Kushner, Giovanna ; Wong, Cynthia ; Akers, Amy ; Zayas-Bazan, Thais ; McCoy, Shelly ; Goyal, Neelam ; Harris, Will ; Gonella, Marie ; Brooks, Benjamin R ; Bravver, Elena ; Sanjak, Mohammed ; Ward, Amber L ; Mehrizi, Amir ; Belfiore, Mark ; Lary, Cynthia ; Nemeth, Joanne ; Conway, Jill ; Holsten, Scott ; Shue, Jamie ; Mitsumoto, Hiroshi ; Youngman, Regina ; Lee, Yei-won ; Dalton, Kate ; Bedlack, Richard S ; Morgenlander, Joel Charles ; Boyette, Candace Lee ; Grace, Karen L ; Thomas Hickey, Patrick ; Perry-Trice, Peggy ; Berry, James ; Atassi, Nazem ; Boylan, Kevin ; Kennelly, Kathleen ; DeSaro, Pamela ; Johnston, Amelia ; Huser, Angela ; Fuqua, Paula ; Staggs, Kristin ; Babcock, Lorraine ; Kryston, Thomas ; Bosch, E Peter ; Verheijde, Josephus L ; Grover, Yvvonne ; Lee, Michael S ; Musil, Danette J ; Whiteman, Dana ; Simpson, Ericka P ; Pleitez, Milvia Y ; Lay, Luis F ; Schwartz, Thomas ; Blanton, Linda ; Lai, Eugene C ; Berry, Nicole ; Khan, Sara ; Chowdhury, Nabi ; Goslin, Kimberly ; Carter, Gregory T ; Ann Kovarik, Mary ; Simionescu, Laura ; Reale, Melissa A ; Markis, Katie ; Money, Kristina ; Boevin, Travis ; Lava, Neil ; Glass, Jonathan D ; Polak, Meraida ; Shaw, Latoya ; Bordeau, Jane ; Rogers, Susan ; Ferguson, Susan ; Kelly, Crystal ; Mozaffar, Tahseen ; Ramsey, Gladys ; Tully, Patricia A ; Alvarez, Rebecca ; Barohn, Richard ; Dimachkie, Mazen M ; Pasnoor, Mamatha ; Herbelin, Laura ; Kasarskis, Edward J ; Dotson, William F ; Sitzlar, Stephen C ; Tandy, Tammy ; Carrico, Jeffery ; Rice, Linda ; Chamblin, Lisa ; Townsend, Janet ; Hanley-Borgia, Lisa ; Vanderpool, Kathryn E ; Taylor, Deborah G ; Hutchinson, Jan ; King, Jason T</creator><creatorcontrib>Miller, Robert G ; Block, Gilbert ; Barohn, Richard J ; Cudkowicz, Merit ; Zhang, Jane R ; McGrath, Michael S ; Appel, Stan H ; Katz, Jonathan ; Kushner, Giovanna ; Wong, Cynthia ; Akers, Amy ; Zayas-Bazan, Thais ; McCoy, Shelly ; Goyal, Neelam ; Harris, Will ; Gonella, Marie ; Brooks, Benjamin R ; Bravver, Elena ; Sanjak, Mohammed ; Ward, Amber L ; Mehrizi, Amir ; Belfiore, Mark ; Lary, Cynthia ; Nemeth, Joanne ; Conway, Jill ; Holsten, Scott ; Shue, Jamie ; Mitsumoto, Hiroshi ; Youngman, Regina ; Lee, Yei-won ; Dalton, Kate ; Bedlack, Richard S ; Morgenlander, Joel Charles ; Boyette, Candace Lee ; Grace, Karen L ; Thomas Hickey, Patrick ; Perry-Trice, Peggy ; Berry, James ; Atassi, Nazem ; Boylan, Kevin ; Kennelly, Kathleen ; DeSaro, Pamela ; Johnston, Amelia ; Huser, Angela ; Fuqua, Paula ; Staggs, Kristin ; Babcock, Lorraine ; Kryston, Thomas ; Bosch, E Peter ; Verheijde, Josephus L ; Grover, Yvvonne ; Lee, Michael S ; Musil, Danette J ; Whiteman, Dana ; Simpson, Ericka P ; Pleitez, Milvia Y ; Lay, Luis F ; Schwartz, Thomas ; Blanton, Linda ; Lai, Eugene C ; Berry, Nicole ; Khan, Sara ; Chowdhury, Nabi ; Goslin, Kimberly ; Carter, Gregory T ; Ann Kovarik, Mary ; Simionescu, Laura ; Reale, Melissa A ; Markis, Katie ; Money, Kristina ; Boevin, Travis ; Lava, Neil ; Glass, Jonathan D ; Polak, Meraida ; Shaw, Latoya ; Bordeau, Jane ; Rogers, Susan ; Ferguson, Susan ; Kelly, Crystal ; Mozaffar, Tahseen ; Ramsey, Gladys ; Tully, Patricia A ; Alvarez, Rebecca ; Barohn, Richard ; Dimachkie, Mazen M ; Pasnoor, Mamatha ; Herbelin, Laura ; Kasarskis, Edward J ; Dotson, William F ; Sitzlar, Stephen C ; Tandy, Tammy ; Carrico, Jeffery ; Rice, Linda ; Chamblin, Lisa ; Townsend, Janet ; Hanley-Borgia, Lisa ; Vanderpool, Kathryn E ; Taylor, Deborah G ; Hutchinson, Jan ; King, Jason T ; Phase 2 Trial NP001 Investigators</creatorcontrib><description>OBJECTIVE: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).
METHODS:This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of <3 yearsʼ 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.
RESULTS: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.
CONCLUSION: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.
CLASSIFICATION OF EVIDENCE: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.</description><identifier>ISSN: 2332-7812</identifier><identifier>EISSN: 2332-7812</identifier><identifier>DOI: 10.1212/NXI.0000000000000100</identifier><identifier>PMID: 25884010</identifier><language>eng</language><publisher>United States: American Academy of Neurology</publisher><ispartof>Neurology : neuroimmunology & neuroinflammation, 2015-06, Vol.2 (3), p.e100-e100</ispartof><rights>2015 American Academy of Neurology</rights><rights>2015 American Academy of Neurology 2015 American Academy of Neurology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2710-daadf3d789b3ced61fcf4a79b11e0d38e898d56353386d797b91695206639d643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396529/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396529/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25884010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miller, Robert G</creatorcontrib><creatorcontrib>Block, Gilbert</creatorcontrib><creatorcontrib>Barohn, Richard J</creatorcontrib><creatorcontrib>Cudkowicz, Merit</creatorcontrib><creatorcontrib>Zhang, Jane R</creatorcontrib><creatorcontrib>McGrath, Michael S</creatorcontrib><creatorcontrib>Appel, Stan H</creatorcontrib><creatorcontrib>Katz, Jonathan</creatorcontrib><creatorcontrib>Kushner, Giovanna</creatorcontrib><creatorcontrib>Wong, Cynthia</creatorcontrib><creatorcontrib>Akers, Amy</creatorcontrib><creatorcontrib>Zayas-Bazan, Thais</creatorcontrib><creatorcontrib>McCoy, Shelly</creatorcontrib><creatorcontrib>Goyal, Neelam</creatorcontrib><creatorcontrib>Harris, Will</creatorcontrib><creatorcontrib>Gonella, Marie</creatorcontrib><creatorcontrib>Brooks, Benjamin R</creatorcontrib><creatorcontrib>Bravver, Elena</creatorcontrib><creatorcontrib>Sanjak, Mohammed</creatorcontrib><creatorcontrib>Ward, Amber L</creatorcontrib><creatorcontrib>Mehrizi, Amir</creatorcontrib><creatorcontrib>Belfiore, Mark</creatorcontrib><creatorcontrib>Lary, Cynthia</creatorcontrib><creatorcontrib>Nemeth, Joanne</creatorcontrib><creatorcontrib>Conway, Jill</creatorcontrib><creatorcontrib>Holsten, Scott</creatorcontrib><creatorcontrib>Shue, Jamie</creatorcontrib><creatorcontrib>Mitsumoto, Hiroshi</creatorcontrib><creatorcontrib>Youngman, Regina</creatorcontrib><creatorcontrib>Lee, Yei-won</creatorcontrib><creatorcontrib>Dalton, Kate</creatorcontrib><creatorcontrib>Bedlack, Richard S</creatorcontrib><creatorcontrib>Morgenlander, Joel Charles</creatorcontrib><creatorcontrib>Boyette, Candace Lee</creatorcontrib><creatorcontrib>Grace, Karen L</creatorcontrib><creatorcontrib>Thomas Hickey, Patrick</creatorcontrib><creatorcontrib>Perry-Trice, Peggy</creatorcontrib><creatorcontrib>Berry, James</creatorcontrib><creatorcontrib>Atassi, Nazem</creatorcontrib><creatorcontrib>Boylan, Kevin</creatorcontrib><creatorcontrib>Kennelly, Kathleen</creatorcontrib><creatorcontrib>DeSaro, Pamela</creatorcontrib><creatorcontrib>Johnston, Amelia</creatorcontrib><creatorcontrib>Huser, Angela</creatorcontrib><creatorcontrib>Fuqua, Paula</creatorcontrib><creatorcontrib>Staggs, Kristin</creatorcontrib><creatorcontrib>Babcock, Lorraine</creatorcontrib><creatorcontrib>Kryston, Thomas</creatorcontrib><creatorcontrib>Bosch, E Peter</creatorcontrib><creatorcontrib>Verheijde, Josephus L</creatorcontrib><creatorcontrib>Grover, Yvvonne</creatorcontrib><creatorcontrib>Lee, Michael S</creatorcontrib><creatorcontrib>Musil, Danette J</creatorcontrib><creatorcontrib>Whiteman, Dana</creatorcontrib><creatorcontrib>Simpson, Ericka P</creatorcontrib><creatorcontrib>Pleitez, Milvia Y</creatorcontrib><creatorcontrib>Lay, Luis F</creatorcontrib><creatorcontrib>Schwartz, Thomas</creatorcontrib><creatorcontrib>Blanton, Linda</creatorcontrib><creatorcontrib>Lai, Eugene C</creatorcontrib><creatorcontrib>Berry, Nicole</creatorcontrib><creatorcontrib>Khan, Sara</creatorcontrib><creatorcontrib>Chowdhury, Nabi</creatorcontrib><creatorcontrib>Goslin, Kimberly</creatorcontrib><creatorcontrib>Carter, Gregory T</creatorcontrib><creatorcontrib>Ann Kovarik, Mary</creatorcontrib><creatorcontrib>Simionescu, Laura</creatorcontrib><creatorcontrib>Reale, Melissa A</creatorcontrib><creatorcontrib>Markis, Katie</creatorcontrib><creatorcontrib>Money, Kristina</creatorcontrib><creatorcontrib>Boevin, Travis</creatorcontrib><creatorcontrib>Lava, Neil</creatorcontrib><creatorcontrib>Glass, Jonathan D</creatorcontrib><creatorcontrib>Polak, Meraida</creatorcontrib><creatorcontrib>Shaw, Latoya</creatorcontrib><creatorcontrib>Bordeau, Jane</creatorcontrib><creatorcontrib>Rogers, Susan</creatorcontrib><creatorcontrib>Ferguson, Susan</creatorcontrib><creatorcontrib>Kelly, Crystal</creatorcontrib><creatorcontrib>Mozaffar, Tahseen</creatorcontrib><creatorcontrib>Ramsey, Gladys</creatorcontrib><creatorcontrib>Tully, Patricia A</creatorcontrib><creatorcontrib>Alvarez, Rebecca</creatorcontrib><creatorcontrib>Barohn, Richard</creatorcontrib><creatorcontrib>Dimachkie, Mazen M</creatorcontrib><creatorcontrib>Pasnoor, Mamatha</creatorcontrib><creatorcontrib>Herbelin, Laura</creatorcontrib><creatorcontrib>Kasarskis, Edward J</creatorcontrib><creatorcontrib>Dotson, William F</creatorcontrib><creatorcontrib>Sitzlar, Stephen C</creatorcontrib><creatorcontrib>Tandy, Tammy</creatorcontrib><creatorcontrib>Carrico, Jeffery</creatorcontrib><creatorcontrib>Rice, Linda</creatorcontrib><creatorcontrib>Chamblin, Lisa</creatorcontrib><creatorcontrib>Townsend, Janet</creatorcontrib><creatorcontrib>Hanley-Borgia, Lisa</creatorcontrib><creatorcontrib>Vanderpool, Kathryn E</creatorcontrib><creatorcontrib>Taylor, Deborah G</creatorcontrib><creatorcontrib>Hutchinson, Jan</creatorcontrib><creatorcontrib>King, Jason T</creatorcontrib><creatorcontrib>Phase 2 Trial NP001 Investigators</creatorcontrib><title>Randomized phase 2 trial of NP001–a novel immune regulator: Safety and early efficacy in ALS</title><title>Neurology : neuroimmunology & neuroinflammation</title><addtitle>Neurol Neuroimmunol Neuroinflamm</addtitle><description>OBJECTIVE: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).
METHODS:This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of <3 yearsʼ 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.
RESULTS: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.
CONCLUSION: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.
CLASSIFICATION OF EVIDENCE: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). 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Jeffery</creator><creator>Rice, Linda</creator><creator>Chamblin, Lisa</creator><creator>Townsend, Janet</creator><creator>Hanley-Borgia, Lisa</creator><creator>Vanderpool, Kathryn E</creator><creator>Taylor, Deborah G</creator><creator>Hutchinson, Jan</creator><creator>King, Jason T</creator><general>American Academy of Neurology</general><general>Lippincott Williams & Wilkins</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201506</creationdate><title>Randomized phase 2 trial of NP001–a novel immune regulator: Safety and early efficacy in ALS</title><author>Miller, Robert G ; Block, Gilbert ; Barohn, Richard J ; Cudkowicz, Merit ; Zhang, Jane R ; McGrath, Michael S ; Appel, Stan H ; Katz, Jonathan ; Kushner, Giovanna ; Wong, Cynthia ; Akers, Amy ; Zayas-Bazan, Thais ; McCoy, Shelly ; Goyal, Neelam ; Harris, Will ; Gonella, Marie ; Brooks, Benjamin R ; Bravver, Elena ; Sanjak, Mohammed ; Ward, Amber L ; Mehrizi, Amir ; Belfiore, Mark ; Lary, Cynthia ; Nemeth, Joanne ; Conway, Jill ; Holsten, Scott ; Shue, Jamie ; Mitsumoto, Hiroshi ; Youngman, Regina ; Lee, Yei-won ; Dalton, Kate ; Bedlack, Richard S ; Morgenlander, Joel Charles ; Boyette, Candace Lee ; Grace, Karen L ; Thomas Hickey, Patrick ; Perry-Trice, Peggy ; Berry, James ; Atassi, Nazem ; Boylan, Kevin ; Kennelly, Kathleen ; DeSaro, Pamela ; Johnston, Amelia ; Huser, Angela ; Fuqua, Paula ; Staggs, Kristin ; Babcock, Lorraine ; Kryston, Thomas ; Bosch, E Peter ; Verheijde, Josephus L ; Grover, Yvvonne ; Lee, Michael S ; Musil, Danette J ; Whiteman, Dana ; Simpson, Ericka P ; Pleitez, Milvia Y ; Lay, Luis F ; Schwartz, Thomas ; Blanton, Linda ; Lai, Eugene C ; Berry, Nicole ; Khan, Sara ; Chowdhury, Nabi ; Goslin, Kimberly ; Carter, Gregory T ; Ann Kovarik, Mary ; Simionescu, Laura ; Reale, Melissa A ; Markis, Katie ; Money, Kristina ; Boevin, Travis ; Lava, Neil ; Glass, Jonathan D ; Polak, Meraida ; Shaw, Latoya ; Bordeau, Jane ; Rogers, Susan ; Ferguson, Susan ; Kelly, Crystal ; Mozaffar, Tahseen ; Ramsey, Gladys ; Tully, Patricia A ; Alvarez, Rebecca ; Barohn, Richard ; Dimachkie, Mazen M ; Pasnoor, Mamatha ; Herbelin, Laura ; Kasarskis, Edward J ; Dotson, William F ; Sitzlar, Stephen C ; Tandy, Tammy ; Carrico, Jeffery ; Rice, Linda ; Chamblin, Lisa ; Townsend, Janet ; Hanley-Borgia, Lisa ; Vanderpool, Kathryn E ; Taylor, Deborah G ; Hutchinson, Jan ; King, Jason T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2710-daadf3d789b3ced61fcf4a79b11e0d38e898d56353386d797b91695206639d643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, Robert G</creatorcontrib><creatorcontrib>Block, Gilbert</creatorcontrib><creatorcontrib>Barohn, Richard J</creatorcontrib><creatorcontrib>Cudkowicz, Merit</creatorcontrib><creatorcontrib>Zhang, Jane R</creatorcontrib><creatorcontrib>McGrath, Michael S</creatorcontrib><creatorcontrib>Appel, Stan H</creatorcontrib><creatorcontrib>Katz, Jonathan</creatorcontrib><creatorcontrib>Kushner, Giovanna</creatorcontrib><creatorcontrib>Wong, Cynthia</creatorcontrib><creatorcontrib>Akers, Amy</creatorcontrib><creatorcontrib>Zayas-Bazan, Thais</creatorcontrib><creatorcontrib>McCoy, Shelly</creatorcontrib><creatorcontrib>Goyal, Neelam</creatorcontrib><creatorcontrib>Harris, Will</creatorcontrib><creatorcontrib>Gonella, Marie</creatorcontrib><creatorcontrib>Brooks, Benjamin R</creatorcontrib><creatorcontrib>Bravver, Elena</creatorcontrib><creatorcontrib>Sanjak, Mohammed</creatorcontrib><creatorcontrib>Ward, Amber L</creatorcontrib><creatorcontrib>Mehrizi, Amir</creatorcontrib><creatorcontrib>Belfiore, Mark</creatorcontrib><creatorcontrib>Lary, Cynthia</creatorcontrib><creatorcontrib>Nemeth, Joanne</creatorcontrib><creatorcontrib>Conway, Jill</creatorcontrib><creatorcontrib>Holsten, Scott</creatorcontrib><creatorcontrib>Shue, Jamie</creatorcontrib><creatorcontrib>Mitsumoto, Hiroshi</creatorcontrib><creatorcontrib>Youngman, Regina</creatorcontrib><creatorcontrib>Lee, Yei-won</creatorcontrib><creatorcontrib>Dalton, Kate</creatorcontrib><creatorcontrib>Bedlack, Richard S</creatorcontrib><creatorcontrib>Morgenlander, Joel Charles</creatorcontrib><creatorcontrib>Boyette, Candace Lee</creatorcontrib><creatorcontrib>Grace, Karen L</creatorcontrib><creatorcontrib>Thomas Hickey, Patrick</creatorcontrib><creatorcontrib>Perry-Trice, Peggy</creatorcontrib><creatorcontrib>Berry, James</creatorcontrib><creatorcontrib>Atassi, Nazem</creatorcontrib><creatorcontrib>Boylan, Kevin</creatorcontrib><creatorcontrib>Kennelly, Kathleen</creatorcontrib><creatorcontrib>DeSaro, Pamela</creatorcontrib><creatorcontrib>Johnston, Amelia</creatorcontrib><creatorcontrib>Huser, Angela</creatorcontrib><creatorcontrib>Fuqua, Paula</creatorcontrib><creatorcontrib>Staggs, Kristin</creatorcontrib><creatorcontrib>Babcock, Lorraine</creatorcontrib><creatorcontrib>Kryston, Thomas</creatorcontrib><creatorcontrib>Bosch, E Peter</creatorcontrib><creatorcontrib>Verheijde, Josephus L</creatorcontrib><creatorcontrib>Grover, Yvvonne</creatorcontrib><creatorcontrib>Lee, Michael S</creatorcontrib><creatorcontrib>Musil, Danette J</creatorcontrib><creatorcontrib>Whiteman, Dana</creatorcontrib><creatorcontrib>Simpson, Ericka P</creatorcontrib><creatorcontrib>Pleitez, Milvia Y</creatorcontrib><creatorcontrib>Lay, Luis F</creatorcontrib><creatorcontrib>Schwartz, Thomas</creatorcontrib><creatorcontrib>Blanton, Linda</creatorcontrib><creatorcontrib>Lai, Eugene C</creatorcontrib><creatorcontrib>Berry, Nicole</creatorcontrib><creatorcontrib>Khan, Sara</creatorcontrib><creatorcontrib>Chowdhury, Nabi</creatorcontrib><creatorcontrib>Goslin, Kimberly</creatorcontrib><creatorcontrib>Carter, Gregory T</creatorcontrib><creatorcontrib>Ann Kovarik, Mary</creatorcontrib><creatorcontrib>Simionescu, Laura</creatorcontrib><creatorcontrib>Reale, Melissa A</creatorcontrib><creatorcontrib>Markis, Katie</creatorcontrib><creatorcontrib>Money, Kristina</creatorcontrib><creatorcontrib>Boevin, Travis</creatorcontrib><creatorcontrib>Lava, Neil</creatorcontrib><creatorcontrib>Glass, Jonathan D</creatorcontrib><creatorcontrib>Polak, Meraida</creatorcontrib><creatorcontrib>Shaw, Latoya</creatorcontrib><creatorcontrib>Bordeau, Jane</creatorcontrib><creatorcontrib>Rogers, Susan</creatorcontrib><creatorcontrib>Ferguson, Susan</creatorcontrib><creatorcontrib>Kelly, Crystal</creatorcontrib><creatorcontrib>Mozaffar, Tahseen</creatorcontrib><creatorcontrib>Ramsey, Gladys</creatorcontrib><creatorcontrib>Tully, Patricia A</creatorcontrib><creatorcontrib>Alvarez, Rebecca</creatorcontrib><creatorcontrib>Barohn, Richard</creatorcontrib><creatorcontrib>Dimachkie, Mazen M</creatorcontrib><creatorcontrib>Pasnoor, Mamatha</creatorcontrib><creatorcontrib>Herbelin, Laura</creatorcontrib><creatorcontrib>Kasarskis, Edward J</creatorcontrib><creatorcontrib>Dotson, William F</creatorcontrib><creatorcontrib>Sitzlar, Stephen C</creatorcontrib><creatorcontrib>Tandy, Tammy</creatorcontrib><creatorcontrib>Carrico, Jeffery</creatorcontrib><creatorcontrib>Rice, Linda</creatorcontrib><creatorcontrib>Chamblin, Lisa</creatorcontrib><creatorcontrib>Townsend, Janet</creatorcontrib><creatorcontrib>Hanley-Borgia, Lisa</creatorcontrib><creatorcontrib>Vanderpool, Kathryn E</creatorcontrib><creatorcontrib>Taylor, Deborah G</creatorcontrib><creatorcontrib>Hutchinson, Jan</creatorcontrib><creatorcontrib>King, Jason T</creatorcontrib><creatorcontrib>Phase 2 Trial NP001 Investigators</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurology : neuroimmunology & neuroinflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, Robert G</au><au>Block, Gilbert</au><au>Barohn, Richard J</au><au>Cudkowicz, Merit</au><au>Zhang, Jane R</au><au>McGrath, Michael S</au><au>Appel, Stan H</au><au>Katz, Jonathan</au><au>Kushner, Giovanna</au><au>Wong, Cynthia</au><au>Akers, Amy</au><au>Zayas-Bazan, Thais</au><au>McCoy, Shelly</au><au>Goyal, Neelam</au><au>Harris, Will</au><au>Gonella, Marie</au><au>Brooks, Benjamin R</au><au>Bravver, Elena</au><au>Sanjak, Mohammed</au><au>Ward, Amber L</au><au>Mehrizi, Amir</au><au>Belfiore, Mark</au><au>Lary, Cynthia</au><au>Nemeth, Joanne</au><au>Conway, Jill</au><au>Holsten, Scott</au><au>Shue, Jamie</au><au>Mitsumoto, Hiroshi</au><au>Youngman, Regina</au><au>Lee, Yei-won</au><au>Dalton, Kate</au><au>Bedlack, Richard S</au><au>Morgenlander, Joel Charles</au><au>Boyette, Candace Lee</au><au>Grace, Karen L</au><au>Thomas Hickey, Patrick</au><au>Perry-Trice, Peggy</au><au>Berry, James</au><au>Atassi, Nazem</au><au>Boylan, Kevin</au><au>Kennelly, Kathleen</au><au>DeSaro, Pamela</au><au>Johnston, Amelia</au><au>Huser, Angela</au><au>Fuqua, Paula</au><au>Staggs, Kristin</au><au>Babcock, Lorraine</au><au>Kryston, Thomas</au><au>Bosch, E Peter</au><au>Verheijde, Josephus L</au><au>Grover, Yvvonne</au><au>Lee, Michael S</au><au>Musil, Danette J</au><au>Whiteman, Dana</au><au>Simpson, Ericka P</au><au>Pleitez, Milvia Y</au><au>Lay, Luis F</au><au>Schwartz, Thomas</au><au>Blanton, Linda</au><au>Lai, Eugene C</au><au>Berry, Nicole</au><au>Khan, Sara</au><au>Chowdhury, Nabi</au><au>Goslin, Kimberly</au><au>Carter, Gregory T</au><au>Ann Kovarik, Mary</au><au>Simionescu, Laura</au><au>Reale, Melissa A</au><au>Markis, Katie</au><au>Money, Kristina</au><au>Boevin, Travis</au><au>Lava, Neil</au><au>Glass, Jonathan D</au><au>Polak, Meraida</au><au>Shaw, Latoya</au><au>Bordeau, Jane</au><au>Rogers, Susan</au><au>Ferguson, Susan</au><au>Kelly, Crystal</au><au>Mozaffar, Tahseen</au><au>Ramsey, Gladys</au><au>Tully, Patricia A</au><au>Alvarez, Rebecca</au><au>Barohn, Richard</au><au>Dimachkie, Mazen M</au><au>Pasnoor, Mamatha</au><au>Herbelin, Laura</au><au>Kasarskis, Edward J</au><au>Dotson, William F</au><au>Sitzlar, Stephen C</au><au>Tandy, Tammy</au><au>Carrico, Jeffery</au><au>Rice, Linda</au><au>Chamblin, Lisa</au><au>Townsend, Janet</au><au>Hanley-Borgia, Lisa</au><au>Vanderpool, Kathryn E</au><au>Taylor, Deborah G</au><au>Hutchinson, Jan</au><au>King, Jason T</au><aucorp>Phase 2 Trial NP001 Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Randomized phase 2 trial of NP001–a novel immune regulator: Safety and early efficacy in ALS</atitle><jtitle>Neurology : neuroimmunology & neuroinflammation</jtitle><addtitle>Neurol Neuroimmunol Neuroinflamm</addtitle><date>2015-06</date><risdate>2015</risdate><volume>2</volume><issue>3</issue><spage>e100</spage><epage>e100</epage><pages>e100-e100</pages><issn>2332-7812</issn><eissn>2332-7812</eissn><abstract>OBJECTIVE: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).
METHODS:This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of <3 yearsʼ 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.
RESULTS: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.
CONCLUSION: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.
CLASSIFICATION OF EVIDENCE: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.</abstract><cop>United States</cop><pub>American Academy of Neurology</pub><pmid>25884010</pmid><doi>10.1212/NXI.0000000000000100</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2332-7812 |
| ispartof | Neurology : neuroimmunology & neuroinflammation, 2015-06, Vol.2 (3), p.e100-e100 |
| issn | 2332-7812 2332-7812 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4396529 |
| source | PubMed (Medline); DOAJ Directory of Open Access Journals; EZB Electronic Journals Library; Wolters Kluwer Open Access; Journals@Ovid Complete |
| title | Randomized phase 2 trial of NP001–a novel immune regulator: Safety and early efficacy in ALS |
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