Practical approaches to dose selection for first-in-human clinical trials with novel biopharmaceuticals

Regulatory Toxicology and Pharmacology

Volumn 58, Issue 2, 2010, Pages 243-251

  Tibbitts, Jay ^a   Cavagnaro, Joy A ^e   Haller, Christine A ^c   Marafino, Ben ^d   Andrews, Paul A ^b   Sullivan, John T ^c  

^a GENENTECH INC   (United States)

^b EISAI INC   (United States)

^c AMGEN INC   (United States)

^d Scientific and Management Consulting   (United States)

^e Access BIO   (United States)

Author keywords

Animal models; Biopharmaceuticals; Biotherapeutics; First in human; Interspecies scaling; MABEL; NOAEL; NOEL; PAD; Safety factor; Safety margin; Toxicology

Indexed keywords

BIOLOGICAL MARKER; CD40 LIGAND MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY; NATALIZUMAB; PANITUMUMAB; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RECOMBINANT MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR; RECOMBINANT THROMBOPOIETIN; ROMIPLOSTIM; TGN 1412; TRASTUZUMAB; TUMOR NECROSIS FACTOR ALPHA;

ADVISORY COMMITTEE; ARTICLE; BINDING AFFINITY; BIOTECHNOLOGY; CARDIOTOXICITY; CLINICAL TRIAL; DOSE CALCULATION; DRUG APPROVAL; DRUG BINDING; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG MECHANISM; DRUG RESEARCH; DRUG SAFETY; DRUG SCREENING; DRUG SELECTIVITY; DRUG TARGETING; HUMAN; IDIOPATHIC THROMBOCYTOPENIC PURPURA; NONHUMAN; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RISK ASSESSMENT; TOXICITY TESTING; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTIBODIES, MONOCLONAL; BIOLOGICAL PRODUCTS; BIOPHARMACEUTICS; BIOTECHNOLOGY; CLINICAL TRIALS AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS;

ANIMALIA;

EID: 77957575471     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2010.06.007     Document Type: Article

References (39)

1. Agoram B.M. Use of pharmacokinetic/ pharmacodynamic modelling for starting dose selection in first-in-human trials of high-risk biologics. Br. J. Clin. Pharmacol. 2009, 67:153-160.
2. Boxenbaum H. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J. Pharmacokinet. Biopharm. 1982, 10:201-227.
3. Braeckman R. Pharmacokinetics and pharmacodynamics of protein therapeutics. Peptide and Protein Drug Analysis 2000, vol. 101:633-669. Marcel Dekker, New York, NY.
4. Bussiere J.L., et al. Alternative strategies for toxicity testing of species-specific biopharmaceuticals. Int. J. Toxicol. 2009, 28:230-253.
5. Cavagnaro J.A. Preclinical safety evaluation of biotechnology-derived pharmaceuticals. Nat. Rev. Drug Discov. 2002, 1:469-475.
6. Colburn W.A. Controversy V: phase I, first time in man studies. J. Clin. Pharmacol. 1990, 30:210-222.
7. De Boer R.H., et al. Pharmacokinetic analysis of pegylated megakaryocyte growth and development factor in humans. Growth Factors 2000, 18:215-226.
8. DeGeorge J.J., et al. Regulatory considerations for preclinical development of anticancer drugs. Cancer Chemother. Pharmacol. 1998, 41:173-185.
9. Dorato M.A., Engelhardt J.A. The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s). Regul. Toxicol. Pharmacol. 2005, 42:265-274.
10. EMA, Scientific Advice Working Party, 2010.
11. EMEA, Note for Guidance on the Pre-clinical Evaluation of Anticancer Medicinal Product. Vol. CPMP/SWP/997/96, 1996.
12. EMEA, Guideline on Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products. Vol. EMEA/CHMP/SWP/28367/07, 2007.
13. Eremina V., et al. VEGF inhibition and renal thrombotic microangiopathy. N. Engl. J. Med. 2008, 358:1129-1136.
14. Expert Scientific Group, Expert Scientific Group on Phase One Clinical Trials. Norwich, UK, 2006.
15. FDA, Food and Drug Administration Guidance for Industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers, 2005.
16. FDA, General Principles EMEA-FDA Parallel Scientific Advice, 2009.
17. Ferrari R. Tumor necrosis factor in CHF: a double facet cytokine. Cardiovasc. Res. 1998, 37:554-559.
18. Guarneri V., et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J. Clin. Oncol. 2006, 24:4107-4115.
19. Harker L.A., et al. Dose-response effects of pegylated human megakaryocyte growth and development factor on platelet production and function in nonhuman primates. Blood 1996, 88:511-521.
20. Horvath C.J., Milton M.N. The TeGenero incident and the Duff Report conclusions: a series of unfortunate events or an avoidable event? Toxicol. Pathol. 2009, 37:372-383.
21. ICH, Preclinical safety evaluation of biotechnology-derived pharmaceuticals (ICH S6). In: CPMP/ICH/384/95, (Ed.), 1997. Available from: <> http://www.ich.org/LOB/media/MEDIA503.pdf.
22. ICH, Addendum to ICH S6: Nonclinical Safety Evaluation of Biotechnology-derived Pharmaceuticals S6(R1) Current Step 2 Version 2009. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/UCM194490.pdf.
23. Kelley S.K., et al. Preclinical pharmacokinetics, pharmacodynamics, and activity of a humanized anti-CD40 antibody (SGN-40) in rodents and non-human primates. Br. J. Pharmacol. 2006, 148:1116-1123.
24. Kuter D.J., Begley C.G. Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. Blood 2002, 100:3457-3469.
25. Le Mauff B., et al. Effect of anti-LFA1 (CD11a) monoclonal antibodies in acute rejection in human kidney transplantation. Transplantation 1991, 52:291-296.
26. Lobo E.D., et al. Application of pharmacokinetic-pharmacodynamic modeling to predict the kinetic and dynamic effects of anti-methotrexate antibodies in mice. J. Pharm. Sci. 2003, 92:1665-1676.
27. McKenzie A.N., et al. Structure-function analysis of interleukin-5 utilizing mouse/human chimeric molecules. EMBO J. 1991, 10:1193-1199.
28. Mordenti J., et al. Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm. Res. 1991, 8:1351-1359.
29. Muller P.Y., Brennan F.R. Safety assessment and dose selection for first-in-human clinical trials with immunomodulatory monoclonal antibodies. Clin. Pharmacol. Ther. 2009, 85:247-258.
30. Muller P.Y., et al. The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies. Curr. Opin. Biotechnol. 2009, 20:722-729.
31. Ransohoff R.M. Natalizumab for multiple sclerosis. N. Engl. J. Med. 2007, 356:2622-2629.
32. Sibille M., et al. After the London tragedy, is it still possible to consider Phase I is safe? Br. J. Clin. Pharmacol. 2006, 62:502-503.
33. Suntharalingam G., et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med. 2006, 355:1018-1028.
34. Tabrizi M.A., et al. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov. Today 2006, 11:81-88.
35. Uchida J., et al. Mouse CD20 expression and function. Int. Immunol. 2004, 16:119-129.
36. Vectibix (panitumumab) Prescribing Information, http://www.vectibix.com.
37. Visich J., Ponce R. Science and judgement in establishing a safe starting dose for first-in-human trials of pharmaceuticals. Preclinical Safety Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials 2008, 971-984. Wiley. J. Cavagnaro (Ed.).
38. Wang B., et al. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin. Pharmacol. Ther. 2004, 76:628-638.
39. Yang B.B., et al. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin. Pharmacol. Ther. 2003, 74:85-94.