Efficacy and Safety of Single-dose Pegfilgrastim for CD34 + Cell Mobilization in Healthy Volunteers: A Phase 2 Study

Abstract

Background: Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers.

Methods: The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 10 6 /L cluster of differentiation 34 positive (CD34 + ) cells.

Results: Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34 + cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34 + mobilization was achieved in all 23 subjects. The mean peripheral blood CD34 + cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation.

Conclusions: A single-dose pegfilgrastim successfully mobilized an optimal number of CD34 + cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).

Graphical abstract

FIGURE 1.

Study design. n, number of subjects. *Based on the discussion with investigator, medical officer, and Efficacy and Safety Assessment Committee, efficacy and safety were assessed and the sponsor made a decision based on this discussion. ^aDose escalation part to determine recommended dose of pegfilgrastim. ^bDose expansion part to assess efficacy and safety of pegfilgrastim. ^cEach dose of pegfilgrastim was administered subcutaneously. ^dAs the CD34⁺ cell count in peripheral blood of all subjects who received 7.2 mg pegfilgrastim exceeded 20/µL with mild AEs, it was deemed unnecessary to proceed to step 3. Therefore, step 3 was abandoned, and the optimal dose of pegfilgrastim was set at 7.2 mg. AE, adverse event; CD34⁺, cluster of differentiation 34 positive; n, number of subjects.

FIGURE 2.

Changes in peripheral blood CD34⁺ cell count during the pilot and evaluation phases (per protocol set) (mean ± SD). CD34⁺, cluster of differentiation 34 positive; n, number of subjects.

FIGURE 3.

Changes in the WBC count during the pilot and evaluation phases (per protocol set) (mean ± SD). n, number of subjects; WBC, white blood cell.

FIGURE 4.

Percent change in the spleen index during the pilot and evaluation phases vs baseline (safety analysis set) (mean ± SD). n, number of subjects.