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A subset of patients in the first two cohorts had additional samples collected at prespecified time points more frequently during the 2 days after the first dose (day 1) and the third dose (day 56).
Further, this short course of treatment only temporarily depleted serum arginine, as expected, which subsequently returned to normal levels 20 days after the last dose (day 40) without further dosing of ADI-PEG20.
Blood samples were obtained from all 10 main study animals per group prior to and 1 h after the seventh dose on Day 21 and at termination, 4 days after the final dose (Day 32).
In each study local and age-appropriate general symptoms were solicited and their occurrence were recorded on diary cards for 7 days after each vaccine dose (day 0-6).
Serum samples collected before vaccination, 21 days after the vaccine dose (day 21) and six months later (month 6) were tested at GSK Biologicals Central Laboratory using a validated in-house hemagglutination inhibition (HI) assay [cut-off: ≥ 1 10] that used chicken erythrocytes as described previously.
Twenty-one days after the first vaccine dose (Day 21), the GMT rose to 136.9, with a vaccine response rate (VRR) of 74%.
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For ALC and heart rate in the phase I multiple-dose study, the maximum attainable effect (Emax) was evaluated on pre-dose day −1 and pre-specified post-dose days.
If tolerability was demonstrated over the first 4 days, the next sequential dose cohort commenced at post-dose day 7 until all six cohorts were completed.
RNA was isolated from patients' peripheral blood samples (rather than PBMC) harvested at the beginning (pre-dose day 1) and end (day 42) of cycle 1.
With FF or VI monotherapy, the day 22 FEV1 was similar to the pre-dose day 1 measure, while with FF/VI therapy, it continued to be elevated compared with the day 1 pre-dose measure (Table 2).
Total RNA was isolated from PBMC prepared from patient's blood samples taken before (pre-dose day 1) and after (pre-dose day 56) administration of SU5416 or corresponding control regimen in a Phase III trial, designated as Trial A. Due to typically low RNA yields, many sample pairs were of insufficient quality for further use (failure rate of at least 1 of 8 samples, or 25% of sample pairs).
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