Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy

BMC Neurology

Volumn 17, Issue 1, 2017, Pages

  Adams, David ^a   Suhr, Ole B ^b   Dyck, Peter J ^c   Litchy, William J ^c   Leahy, Raina G ^d   Chen, Jihong ^d   Gollob, Jared ^d   Coelho, Teresa ^e  

^a BICÊTRE HOSPITAL   (France)

^b UMEÅ UNIVERSITY HOSPITAL   (Sweden)

^c MAYO CLINIC   (United States)

^d ALNYLAM PHARMACEUTICALS   (United States)

^e HOSPITAL DE SANTO ANTÓNIO   (Portugal)

Author keywords

APOLLO; HATTR amyloidosis; Methods; MNIS+7; Patisiran; Polyneuropathy; RNA interference

Indexed keywords

PATISIRAN; PLACEBO; SMALL INTERFERING RNA;

ADULT; AGED; ARTICLE; ATTR AMYLOIDOSIS; AUTONOMIC NERVOUS SYSTEM FUNCTION; BODY MASS; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE BURDEN; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; FAMILIAL AMYLOID POLYNEUROPATHY; HEART FUNCTION; HUMAN; MENTAL DISEASE ASSESSMENT; MOTOR PERFORMANCE; MULTICENTER STUDY; MUSCLE REFLEX; NERVE CONDUCTION; NUTRITIONAL STATUS; PHASE 3 CLINICAL TRIAL; QUALITY OF LIFE; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; SENSATION; SURVIVAL PREDICTION; WALK TEST; ADOLESCENT; AMYLOIDOSIS; CLINICAL TRIAL; DIABETIC NEUROPATHY; MIDDLE AGED; POLYNEUROPATHY; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; AMYLOIDOSIS; BODY MASS INDEX; DIABETIC NEUROPATHIES; DOUBLE-BLIND METHOD; HUMANS; MIDDLE AGED; NEURAL CONDUCTION; POLYNEUROPATHIES; QUALITY OF LIFE; RNA, SMALL INTERFERING; SURVEYS AND QUESTIONNAIRES; YOUNG ADULT;

EID: 85029320430     PISSN: None     EISSN: 14712377     Source Type: Journal    
DOI: 10.1186/s12883-017-0948-5     Document Type: Article

References (70)

1. Hanna M. Novel drugs targeting transthyretin amyloidosis. Curr Heart Fail Rep. 2014;11(1):50-7.
2. Hawkins PN, Ando Y, Dispenzeri A, Gonzalez-Duarte A, Adams D, Suhr OB. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47(8):625-38.
3. Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76.
4. Mohty D, Damy T, Cosnay P, Echahidi N, Casset-Senon D, Virot P, Jaccard A. Cardiac amyloidosis: updates in diagnosis and management. Arch Cardiovasc Dis. 2013;106(10):528-40.
5. Conceicao I, Gonzalez-Duarte A, Obici L, Schmidt HH, Simoneau D, Ong ML, Amass L. "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016;21(1):5-9.
6. Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med. 2012;79(6):733-48.
7. Coutinho P, DeSilva A, Lima J, Barbosa A. Forty years of experience with type I amyloid neuropathy: review of 483 cases. In: Glenner G, Costa P, de Freitas A, editors. Amyloid and Amyloidosis. Amsterdam: Excerpta Medica; 1980. pp. 88-98.
8. Ando Y, Coelho T, Berk JL, Cruz MW, Ericzon BG, Ikeda S, Lewis WD, Obici L, Plante-Bordeneuve V, Rapezzi C, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31.
9. Koike H, Tanaka F, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, Fujitake J, Kawanami T, Kato T, Yamamoto M, et al. Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas. J Neurol Neurosurg Psychiatry. 2012;83(2):152-8.
10. Planté-Bordeneuve V, Said G. Familial amyloid polyneuropathy. Lancet Neurol. 2011;10(12):1086-97.
11. Benson MD, Teague SD, Kovacs R, Feigenbaum H, Jung J, Kincaid JC. Rate of progression of transthyretin amyloidosis. Am J Cardiol. 2011;108(2):285-9.
12. Mariani LL, Lozeron P, Theaudin M, Mincheva Z, Signate A, Ducot B, Algalarrondo V, Denier C, Adam C, Nicolas G, et al. Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France. Ann Neurol. 2015;78(6):901-16.
13. Sattianayagam PT, Hahn AF, Whelan CJ, Gibbs SD, Pinney JH, Stangou AJ, Rowczenio D, Pflugfelder PW, Fox Z, Lachmann HJ, et al. Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant. Eur Heart J. 2012;33(9):1120-7.
14. Rowczenio DM, Noor I, Gillmore JD, Lachmann HJ, Whelan C, Hawkins PN, Obici L, Westermark P, Grateau G, Wechalekar AD. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014;35(9):E2403-12.
15. Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126(10):1286-300.
16. Maurer MS, Hanna M, Grogan M, Dispenzieri A, Witteles R, Drachman B, Judge DP, Lenihan DJ, Gottlieb SS, Shah SJ, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-72.
17. Suanprasert N, Berk JL, Benson MD, Dyck PJ, Klein CJ, Gollob JA, Bettencourt BR, Karsten V, Dyck PJ. Retrospective study of a TTR FAP cohort to modify NIS+7 for therapeutic trials. J Neurol Sci. 2014;344(1-2):121-8.
18. Andrade C. A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain. 1952;75(3):408-27.
19. Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, Plante-Bordeneuve V, Lozeron P, Suhr OB, Campistol JM, Conceicao IM, Schmidt HH, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2012;79(8):785-92.
20. Vinik EJ, Vinik AI, Paulson JF, Merkies IS, Packman J, Grogan DR, Coelho T. Norfolk QOL-DN: validation of a patient reported outcome measure in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2014;19(2):104-14.
21. Coelho T, Vinik A, Vinik EJ, Tripp T, Packman J, Grogan DR. Clinical measures in transthyretin familial amyloid polyneuropathy. Muscle Nerve. 2017;55(3):323-32.
22. Inês M, Coelho T, Conceição I, Ferreira L, de Carvalho M, Costa J. Transthyretin familial amyloid polyneuropathy impact on health-related quality of life. Orphanet J Rare Dis. 2015;10(Supp. 1):O28.
23. Wixner J, Mundayat R, Karayal ON, Anan I, Karling P, Suhr OB, THAOS investigators. THAOS: gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease. Orphanet J Rare Dis. 2014;9:61.
24. Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, Heneghan MA, Gorevic PD, Litchy WJ, Wiesman JF, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310(24):2658-67.
25. Mita S, Maeda S, Shimada K, Araki S. Analyses of prealbumin mRNAs in individuals with familial amyloidotic polyneuropathy. J Biochem. 1986;100(5):1215-22.
26. Holmgren G, Steen L, Ekstedt J, Groth CG, Ericzon BG, Eriksson S, Andersen O, Karlberg I, Norden G, Nakazato M, et al. Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30). Clin Genet. 1991;40(3):242-6.
27. Adams D, Samuel D, Goulon-Goeau C, Nakazato M, Costa PM, Feray C, Plante V, Ducot B, Ichai P, Lacroix C, et al. The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation. Brain. 2000;123(Pt 7):1495-504.
28. Ericzon BG, Wilczek HE, Larsson M, Wijayatunga P, Stangou A, Pena JR, Furtado E, Barroso E, Daniel J, Samuel D, et al. Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative? Transplantation. 2015;99(9):1847-54.
29. Suhr OB, Larsson M, Ericzon BG, Wilczek HE, on behalf of the FAPWTR's investigators. Survival after transplantation in patients with mutations other than Val30Met: extracts from the FAP World Transplant Registry. Transplantation. 2016;100(2):373-81.
30. Carvalho A, Rocha A, Lobato L. Liver transplantation in transthyretin amyloidosis: issues and challenges. Liver Transpl. 2015;21(3):282-92.
31. Adams D, Buades J, Suhr O, Obici L, Coelho T. Preliminary assessment of neuropathy progression in patients with hereditary ATTR amyloidosis after orthotopic liver transplantation. Orphanet J Rare Dis. 2015;10(Suppl. 1):P19.
32. Liepnieks JJ, Zhang LQ, Benson MD. Progression of transthyretin amyloid neuropathy after liver transplantation. Neurology. 2010;75(4):324-7.
33. EMA. Vyndaqel [ http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002294/human_med_001498.jsp&mid=WC0b01ac058001d124 ].
34. Amyloidosis Patient Information Site. National Amyloidosis Centre. ATTR Anyloidosis. [ http://www.amyloidosis.org.uk/introduction-to-attr-amyloidosis/2015 ].
35. Coelho T, Maia LF, da Silva AM, Cruz MW, Plante-Bordeneuve V, Suhr OB, Conceicao I, Schmidt HH, Trigo P, Kelly JW, et al. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol. 2013;260(11):2802-14.
36. Plante-Bordeneuve V, Gorram F, Salhi H, Nordine T, Ayache SS, Le Corvoisier P, Azoulay D, Feray C, Damy T, Lefaucheur JP. Long-term treatment of transthyretin familial amyloid polyneuropathy with tafamidis: a clinical and neurophysiological study. J Neurol. 2017;264(2):268-76.
37. Cortese A, Vita G, Luigetti M, Russo M, Bisogni G, Sabatelli M, Manganelli F, Santoro L, Cavallaro T, Fabrizi GM, et al. Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area. J Neurol. 2016;263(5):916-24.
38. Lozeron P, Theaudin M, Mincheva Z, Ducot B, Lacroix C, Adams D, French Network for FAP (CORNAMYL). Effect on disability and safety of Tafamidis in late onset of Met30 transthyretin familial amyloid polyneuropathy. Eur J Neurol. 2013;20(12):1539-45.
39. Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013;369(9):819-29.
40. Okamoto S, Wixner J, Obayashi K, Ando Y, Ericzon BG, Friman S, Uchino M, Suhr OB. Liver transplantation for familial amyloidotic polyneuropathy: impact on Swedish patients' survival. Liver Transpl. 2009;15(10):1229-35.
41. Tashima K, Ando Y, Terazaki H, Yoshimatsu S, Suhr OB, Obayashi K, Yamashita T, Ando E, Uchino M, Ando M. Outcome of liver transplantation for transthyretin amyloidosis: follow-up of Japanese familial amyloidotic polyneuropathy patients. J Neurol Sci. 1999;171(1):19-23.
42. Gillmore JD, Lovat LB, Persey MR, Pepys MB, Hawkins PN. Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid a protein. Lancet. 2001;358(9275):24-9.
43. Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, Hawkins PN. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol. 2003;122(1):78-84.
44. Gillmore JD, Stangou AJ, Tennent GA, Booth DR, O'Grady J, Rela M, Heaton ND, Wall CA, Keogh JA, Hawkins PN. Clinical and biochemical outcome of hepatorenal transplantation for hereditary systemic amyloidosis associated with apolipoprotein AI Gly26Arg. Transplantation. 2001;71(7):986-92.
45. Suhr OB, Coelho T, Buades J, Pouget J, Conceicao I, Berk J, Schmidt H, Waddington-Cruz M, Campistol JM, Bettencourt BR, et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015;10:109.
46. Suhr O, Adams D, Coelho T, Waddington Cruz M, Schmidt H, Buades J, Campistol J, Pouget J, Berk J, Polydefkis M, et al. Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the tereatment of hereditary ATTR amyloidosis with polyneuropathy. In: The XVth International Symposium on Amyloidosis (International Society of Amyloidosis) Uppsala: Abstract PA80; 2016.
47. Adams D, Coelho T, Obici L, Merlini G, Mincheva Z, Suanprasert N, Bettencourt BR, Gollob JA, Gandhi PJ, Litchy WJ, et al. Rapid progression of familial amyloidotic polyneuropathy: a multinational natural history study. Neurology. 2015;85(8):675-82.
48. Dyck PJ, Herrmann DN, Staff NP, Dyck PJ. Assessing decreased sensation and increased sensory phenomena in diabetic polyneuropathies. Diabetes. 2013;62(11):3677-86.
49. Vinik EJ, Hayes RP, Oglesby A, Bastyr E, Barlow P, Ford-Molvik SL, Vinik AI. The development and validation of the Norfolk QOL-DN, a new measure of patients' perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther. 2005;7(3):497-508.
50. EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208.
51. Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W. COMPASS 31: a refined and abbreviated composite autonomic symptom score. Mayo Clin Proc. 2012;87(12):1196-201.
52. van Nes SI, Vanhoutte EK, van Doorn PA, Hermans M, Bakkers M, Kuitwaard K, Faber CG, Merkies IS. Rasch-built overall disability scale (R-ODS) for immune-mediated peripheral neuropathies. Neurology. 2011;76(4):337-45.
53. Suhr O, Danielsson A, Holmgren G, Steen L. Malnutrition and gastrointestinal dysfunction as prognostic factors for survival in familial amyloidotic polyneuropathy. J Intern Med. 1994;235(5):479-85.
54. Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, Edwards RR, Freeman R, Gracely R, Haanpaa MH, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013;154(9):1807-19.
55. Cruz-Almeida Y, Fillingim RB. Can quantitative sensory testing move us closer to mechanism-based pain management? Pain Med. 2014;15(1):61-72.
56. Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial. Muscle Nerve. 2017. doi: 10.1002/mus.25563. [Epub ahead of print].
57. Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. Am Fam Physician. 2011;84(5):527-36.
58. Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJ, O'Brien PC, Cl vs. NPhys Trial Investigators, Albers JW, Andersen H, et al. Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial. Muscle Nerve. 2010;42(2):157-64.
59. Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJ, Carter RE, Melton LJ, Andersen H, Albers JW, et al. "Unequivocally abnormal" vs "usual" signs and symptoms for proficient diagnosis of diabetic polyneuropathy: Cl vs N Phys trial. Arch Neurol. 2012;69(12):1609-14.
60. Dyck PJ, Albers JW, Wolfe J, Bolton CF, Walsh N, Klein CJ, Zafft AJ, Russell JW, Thomas K, Davies JL, et al. A trial of proficiency of nerve conduction: greater standardization still needed. Muscle Nerve. 2013;48(3):369-74.
61. Litchy WJ, Albers JW, Wolfe J, Bolton CF, Walsh N, Klein CJ, Zafft AJ, Russell JW, Zwirlein M, Overland CJ, et al. Proficiency of nerve conduction using standard methods and reference values (cl. NPhys trial 4). Muscle Nerve. 2014;50(6):900-8.
62. Dyck PJ, Argyros B, Russell JW, Gahnstrom LE, Nalepa S, Albers JW, Lodermeier KA, Zafft AJ, Dyck PJ, Klein CJ, et al. Multicenter trial of the proficiency of smart quantitative sensation tests. Muscle Nerve. 2014;49(5):645-53.
63. Li H, Schwartz J, Keohane D. Impact of baseline neurologic score on disease progression in transthyretin familial amyloid polyneuropathy. In: International Society of Amyloidosis (ISA). Uppsala: Poster PB2; 2016.
64. Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, et al. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054-60.
65. Shy ME, Chen L, Swan ER, Taube R, Krajewski KM, Herrmann D, Lewis RA, McDermott MP. Neuropathy progression in Charcot-Marie-tooth disease type 1A. Neurology. 2008;70(5):378-83.
66. Coelho T, Suhr O, Conceicao I, Waddington Cruz M, Schmidt H, Buades J, Campistol J, Pouget J, Berk J, Ziyadeh N, et al. Relationship between TTR knockdown and change in mNIS+7: preliminary correlation findings from the Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for hereditary ATTR amyloidosis with polyneuropathy. In: The XVth International Symposium on Amyloidosis (Internation Society of Amyloidosis). Uppsala: Poster PA83; 2016.
67. Ueda M, Ando Y. Recent advances in transthyretin amyloidosis therapy. Transl Neurodegener. 2014;3:19.
68. Amyloidosis Foundation: Understanding the patient voice in hereditary transthyretin-mediated amyloidosis. Chicago: Amyloidosis Foundation & Amyloidosis Support Groups Annual Meeting; 2015.
69. Pruppers MH, Merkies IS, Faber CG, Da Silva AM, Costa V, Coelho T. The Val30Met familial amyloid polyneuropathy specific Rasch-built overall disability scale (FAP-RODS(c)). J Peripher Nerv Syst. 2015;20(3):319-27.
70. Chao CC, Huang CM, Chiang HH, Luo KR, Kan HW, Yang NC, Chiang H, Lin WM, Lai SM, Lee MJ, et al. Sudomotor innervation in transthyretin amyloid neuropathy: pathology and functional correlates. Ann Neurol. 2015;78(2):272-83.