SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis.

BACKGROUND

Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.

OBJECTIVES

We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).

DESIGN

SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.

METHODS

Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3 lymphocyte count. Secondary endpoints: PD and PK parameters.

RESULTS

Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3 cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3 cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death.

CONCLUSION

In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment.

TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT02583594.