Question 2: What are the mean serum adalimumab trough concentrations at Weeks 0, 2, 4, 8, 32 and 52 in Study M06-827 when the 24 non-GCP compliant subjects are included in the analyses (by randomised treatment group and dose)? Sponsor’s response: In Table 14 of its response, the Sponsor provided a summary of serum adalimumab trough concentrations by dose in all subjects with ulcerative colitis i.e. including the 24 non-GCP compliant subjects. Clinical comment to response: Inclusion of the 24 non-GCP compliant subjects in the analyses did not affect the mean adalimumab trough concentration through the 52-week study period. Question 3: What are the results of the primary efficacy endpoints and first ranked secondary endpoint when the 24 non-GCP compliant subjects are included in the primary analysis (ITT) set in Study M06-827? Sponsor’s response: In Table 15 of its response, the Sponsor has provided the results of the co-primary and ranked secondary efficacy endpoints of Study MO6-827 which included the 24 non-GCP compliant subjects. Clinical comment on response: The results were consistent with the primary and secondary efficacy analyses in Study Question 4: What was the baseline AAA, HACA and anti-TNF status for the non-GCP subjects (by randomised treatment group)? Sponsor’s response: In Table 16 of its response, the Sponsor provided the results of baseline AAA, HACA and status for the 24 non-GCP subjects by randomised treatment group versus the ITT population. One of the anti-TNF naive subjects developed AAA (measured at Week 32). Clinical comment to response: The 24 non-GCP subjects generally had lower rates in all three parameters compared with the ITT population and therefore their exclusion from the primary ITT population is unlikely to adversely affect the overall efficacy results. Note: Questions and evaluation of responses regarding the PI and CMI are not included in this Extract from the Clinical Evaluation Report Final round evaluation of clinical data submitted in response to questions The Sponsor’s responses to the Clinical Questions are generally considered satisfactory. There are no further clinical questions relating to this submission.
Question 2: What are the mean serum adalimumab trough concentrations at Weeks 0, 2, 4, 8, 32 and 52 in Study M06-827 when the 24 non-GCP compliant subjects are included in the analyses (by randomised treatment group and dose)? Sponsor’s response: In Table 14 of its response, the Sponsor provided a summary of serum adalimumab trough concentrations by dose in all subjects with ulcerative colitis i.e. including the 24 non-GCP compliant subjects. Clinical comment to response: Inclusion of the 24 non-GCP compliant subjects in the analyses did not affect the mean adalimumab trough concentration through the 52-week study period. Question 3: What are the results of the primary efficacy endpoints and first ranked secondary endpoint when the 24 non-GCP compliant subjects are included in the primary analysis (ITT) set in Study M06-827? Sponsor’s response: In Table 15 of its response, the Sponsor has provided the results of the co-primary and ranked secondary efficacy endpoints of Study MO6-827 which included the 24 non-GCP compliant subjects. Clinical comment on response: The results were consistent with the primary and secondary efficacy analyses in Study Question 4: What was the baseline AAA, HACA and anti-TNF status for the non-GCP subjects (by randomised treatment group)? Sponsor’s response: In Table 16 of its response, the Sponsor provided the results of baseline AAA, HACA and status for the 24 non-GCP subjects by randomised treatment group versus the ITT population. One of the anti-TNF naive subjects developed AAA (measured at Week 32). Clinical comment to response: The 24 non-GCP subjects generally had lower rates in all three parameters compared with the ITT population and therefore their exclusion from the primary ITT population is unlikely to adversely affect the overall efficacy results. Note: Questions and evaluation of responses regarding the PI and CMI are not included in this Extract from the Clinical Evaluation Report Final round evaluation of clinical data submitted in response to questions The Sponsor’s responses to the Clinical Questions are generally considered satisfactory. There are no further clinical questions relating to this submission.
auspar-adalimumab-131025-cer.docx