5: Five studies providing efficacy data. Design Patients Primary objectives Secondary objectives II Phase II, prospective, randomised, open-label, multi-centre. Start: 27/04/2012 End: 18/09/2012. 22 adult PTPs enrolled: all 22 in ITT and SAF and 14 in the PP population Determine the PKs of simoctocog alfa and compare with PKs of full-length rFVIII BHK Calculate incremental recovery; Investigate immunogenicity; Assess clinical efficacy and safety in the treatment of BEs and in surgical prophylaxis. III Phase III, prospective, multinational, multicentre, open-label, single-arm. Start: 22/07/2010. End: 31/01/2012. 32 PTPs enrolled: all 32 in ITT and SAF Determine the efficacy of simoctocog alfa during prophylactic treatment, treatment of BEs and in surgical prophylaxis. Calculate incremental recovery; Investigate immunogenicity; Assess safety. III Phase III, prospective, multinational, multicentre, open-label, Start: 27/12/2010. End: 06/11/2012. 59 paediatric PTPs enrolled; all 59 patients were analysed for efficacy; patients aged from 2 to 12 (inclusive). Assess clinical efficacy of simoctocog alfa in terms of prevention & treatment of BEs. Determine PKs; Determine incremental recovery; Investigate immunogenicity; Assess efficacy in surgical procedures; Assess safety by AE monitoring. II Phase II, prospective, single-centre, open-label, randomised cross-over PK part and uncontrolled efficacy part. 22 adult PTPs enrolled: all 22 were included in the analyses (safety, ITT, PROPH • Determine the PKs of simoctocog alfa and compare with previously used rFVIII BHK. Calculate incremental recovery. Investigate immunogenicity. Assess clinical efficacy and safety during populations
mutations and therefore, it is recommended that the sponsor adds ‘Safety and tolerability in patients with high risk gene mutations’ as missing information in the of ongoing safety concerns. observed in any of these patients. ‘Safety in patients with HIV or infections’ has been included as missing information in the appropriate Sections of the RMP. 2.7) ‘Medication including safety in home therapy setting’ has already been included as a potential risk in the Risk Management Plan in response to the evaluation of the RMP by EMA. 2.8) ‘Safety in patients with high risk gene mutations’ has been included as missing information in the appropriate Sections of the RMP. address this safety concern is considered acceptable. 2.8.) The addition of this ongoing safety concern to the table of ongoing safety concerns is considered acceptable. However, it is recommended to the Delegate that the wording used to address this ongoing safety concern in the PI be revised.* * The sponsor has proposed to use the same generic wording to address all safety concerns in the PI and CMI. This is considered not acceptable as it does not inform the health care professional and the patient about the absence of clinical data which could inform these ongoing safety concerns. It is recommended that the sponsor amends the PI and CMI to provide more precise 3. It is recommended that the pharmacovigilance section of the ASA be amended to include reference to the TGA document ‘Australian requirements and recommendations for pharmacovigilance responsibilities of sponsors of medicines’, Version 1.1, December 2012. Section 2 ‘Pharmacovigilance Practice’ of the ASA has been amended to include reference to the TGA document ‘Australian requirements and recommendations for pharmacovigilance responsibilities of sponsors of medicines’, Version 1.2, August 2013. This is considered acceptable.