An Open Label Study of CM-AT for the Treatment of Children With Autism

Phase 3 Active not recruiting 405 enrolled Curemark

NaSingle-groupOpen-labelTreatment

Summary

This is a Phase III, open label extension study evaluating the continued safety and efficacy of CM-AT in pediatric patients with autism with all levels of fecal chymotrypsin.

Timeline

Start: 2015-10
Primary completion: 2028-01
Completion: 2028-01

Outcome

Met primary endpoint

paper statistically significant differences of -2.49 (95% CI, -4.66 to -0.32; Cohen d = 0.364; P = .03) at the 12-week timepoint PMID 38032645 ↗

paper This cohort study of preschool children sustained cumulative reduction in the maladaptive behavior of irritability in autism. PMID 38032645 ↗

Publications

Background McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, Veenstra-Vanderweele J. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics. 2011 May;127(5):e1312-21. doi: 10.1542/peds.2011-0427. Epub 2011 Apr 4.
Background Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 2012 Mar 30;61(3):1-19.
Background Baio, J. Prevalence of Autism Spectrum Disorders - Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States.(2010). Retrieved from http://www.cdc.gov/mmwr/pdf/ss/ss6302.pdf
Background Peacock G, Amendah D, Ouyang L, Grosse SD. Autism spectrum disorders and health care expenditures: the effects of co-occurring conditions. J Dev Behav Pediatr. 2012 Jan;33(1):2-8. doi: 10.1097/DBP.0b013e31823969de.
Background Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med. 2007 Apr;161(4):343-9. doi: 10.1001/archpedi.161.4.343.
Background McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014 May;133(5):872-83. doi: 10.1542/peds.2013-3995.
Background Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan;125 Suppl 1:S1-18. doi: 10.1542/peds.2009-1878C.
Background Samsam M, Ahangari R, Naser SA. Pathophysiology of autism spectrum disorders: revisiting gastrointestinal involvement and immune imbalance. World J Gastroenterol. 2014 Aug 7;20(29):9942-51. doi: 10.3748/wjg.v20.i29.9942.
Background Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C, Montiel-Nava C, Patel V, Paula CS, Wang C, Yasamy MT, Fombonne E. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 2012 Jun;5(3):160-79. doi: 10.1002/aur.239. Epub 2012 Apr 11.
Background Wasfy M, Oyofo B, Elgindy A, Churilla A. Comparison of preservation media for storage of stool samples. J Clin Microbiol. 1995 Aug;33(8):2176-8. doi: 10.1128/jcm.33.8.2176-2178.1995.
Background Cavallini G, Benini L, Brocco G, Riela A, Bovo P, Pederzoli P, Angelini G, Pelle C, Bertelli G, Scuro LA. The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests. Pancreas. 1989;4(3):300-4. doi: 10.1097/00006676-198906000-00005.
Background Matthews DM. Intestinal absorption of amino acids and peptides. Proc Nutr Soc. 1972 Sep;31(2):171-7. doi: 10.1079/pns19720033. No abstract available.
Background Coutinho AM, Oliveira G, Morgadinho T, Fesel C, Macedo TR, Bento C, Marques C, Ataide A, Miguel T, Borges L, Vicente AM. Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Mol Psychiatry. 2004 Mar;9(3):264-71. doi: 10.1038/sj.mp.4001409.
Background Naushad SM, Jain JM, Prasad CK, Naik U, Akella RR. Autistic children exhibit distinct plasma amino acid profile. Indian J Biochem Biophys. 2013 Oct;50(5):474-8.
Background Williams K, Wheeler DM, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2010 Aug 4;(8):CD004677. doi: 10.1002/14651858.CD004677.pub2.
Background Tang G, Gudsnuk K, Kuo SH, Cotrina ML, Rosoklija G, Sosunov A, Sonders MS, Kanter E, Castagna C, Yamamoto A, Yue Z, Arancio O, Peterson BS, Champagne F, Dwork AJ, Goldman J, Sulzer D. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 2014 Sep 3;83(5):1131-43. doi: 10.1016/j.neuron.2014.07.040. Epub 2014 Aug 21.
Background Balasubramanian MN, Butterworth EA, Kilberg MS. Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am J Physiol Endocrinol Metab. 2013 Apr 15;304(8):E789-99. doi: 10.1152/ajpendo.00015.2013. Epub 2013 Feb 12.
Background Fairclough PD, Hegarty JE, Silk DB, Clark ML. Comparison of the absorption of two protein hydrolysates and their effects on water and electrolyte movements in the human jejunum. Gut. 1980 Oct;21(10):829-34. doi: 10.1136/gut.21.10.829.
Background Arnold GL, Hyman SL, Mooney RA, Kirby RS. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003 Aug;33(4):449-54. doi: 10.1023/a:1025071014191.
Background Munasinghe SA, Oliff C, Finn J, Wray JA. Digestive enzyme supplementation for autism spectrum disorders: a double-blind randomized controlled trial. J Autism Dev Disord. 2010 Sep;40(9):1131-8. doi: 10.1007/s10803-010-0974-2.
Background Schreck KA, Williams K, Smith AF. A comparison of eating behaviors between children with and without autism. J Autism Dev Disord. 2004 Aug;34(4):433-8. doi: 10.1023/b:jadd.0000037419.78531.86.
Background Bailey DB Jr, Raspa M, Olmsted M, Holiday DB. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am J Med Genet A. 2008 Aug 15;146A(16):2060-9. doi: 10.1002/ajmg.a.32439.
Background Lecavalier L. An evaluation of the Gilliam Autism Rating Scale. J Autism Dev Disord. 2005 Dec;35(6):795-805. doi: 10.1007/s10803-005-0025-6.
Background Marcus RN, Owen R, Kamen L, Manos G, McQuade RD, Carson WH, Aman MG. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-1119. doi: 10.1097/CHI.0b013e3181b76658.
Background Yerys BE, Wallace GL, Sokoloff JL, Shook DA, James JD, Kenworthy L. Attention deficit/hyperactivity disorder symptoms moderate cognition and behavior in children with autism spectrum disorders. Autism Res. 2009 Dec;2(6):322-33. doi: 10.1002/aur.103.
Background Schreck KA, Williams K. Food preferences and factors influencing food selectivity for children with autism spectrum disorders. Res Dev Disabil. 2006 Jul-Aug;27(4):353-63. doi: 10.1016/j.ridd.2005.03.005. Epub 2005 Jul 25.
Background Borowitz D. Update on the evaluation of pancreatic exocrine status in cystic fibrosis. Curr Opin Pulm Med. 2005 Nov;11(6):524-7. doi: 10.1097/01.mcp.0000181474.08058.b3.
Background Penn AH, Hugli TE, Schmid-Schonbein GW. Pancreatic enzymes generate cytotoxic mediators in the intestine. Shock. 2007 Mar;27(3):296-304. doi: 10.1097/01.shk.0000235139.20775.7f.
Pearson DA, Hendren RL, Heil MF, McIntyre WR, Raines SR. Pancreatic Replacement Therapy for Maladaptive Behaviors in Preschool Children With Autism Spectrum Disorder. JAMA Netw Open. 2023 Nov 1;6(11):e2344136. doi: 10.1001/jamanetworkopen.2023.44136.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	CM-AT	Protein / enzyme biologic	900 mg	—