Abstract Body: Introduction: The HEMERA-1 showed safety and early efficacy signals in the completed MT only (excluding IVT) subjects. Here, we present safety & efficacy data from the recently completed part-2 extension which included subjects with IVT± MT as well provide recruitment & interim safety updates on the Part 3 (dual dose) extension.
Methods: HEMERA 1 is an open label, multi-center, phase 1 safety and efficacy clinical trial of PP-007 in patient with AIS with large vessel occlusion (LVO) (ClinicalTrials.gov NCT04677777). Part 2 subjects included IVT to the treatment options for standard of care (SOC). Ongoing part 3 also includes MT± IVT but lowered ASPECTS inclusion from ≥ 5 to ≥ 3 and two PP-007 doses administered 24 h apart (320 mg/kg over 2 hour infusion). Primary safety measure included symptomatic intracranial hemorrhage rates. Efficacy measures included early outcomes (NIHSS 24 h 7-day) and extended outcomes (dichotomized day-90 mRS 0-2).
Results: HEMERA-1 enrollment included 48 subjects receiving PP-007 with 12 completed in Part 2 and 11 out of 24 in enrolled in Part 3 so far. Outcome measures for safety and efficacy were determined for all subjects. No study related SAE’s were reported for Part 2 enrollees including sICH. Part 2 NIHSS data showed a > -7 to > -10 point change in 24 h, 7 and 90 d, respectively. The 90 d mRS showed 83% overall improvements with a breakdown for LVO of 78% (MT + IVT) 71% (IVT Only) and 100% for non-LVO (IVT only). Interim Part 3 Safety data with two doses also did not show PP-007 related SAEs or sICH. PK values for Part 2 were 4.39 and 2.83 mg/mL, 2 and 24 h respectively. The drug levels for Part 3 after first dose were 4.2 and 2.45 mg/mL (2 and 24 h) and following the second dose were 5.9 and 4.1 mg/mL (2 and 24 h or 26 and 48 h following first dose).
Conclusions: Overall, the drug product has exhibited good safety and tolerability across all three treatment parts similar to previously completed PP-007 clinical trials. The improvement of NIHSS and mRS outcomes were limited in sample size but encouraging in this Ph1 setting compared to placebo rate (~48% 90-day mRs 0-2) shown in LVO MT trials metanalysis. PK data showed similar results to prior studies with high drug levels through first 24 hrs. The additional second dose increased the area under the curve and indicated good drug exposure was likely for ≥72 h which is significantly longer than most cerebroprotectants and may provide additional extended benefits.