DX41
Routine Laboratory Measures in the Controlled Treatment Period of Phase III Ocrelizumab Trials in Relapsing and Progressive Multiple Sclerosis
Ocrelizumab (OCR) demonstrated a favorable benefit–risk profile in the Phase III trials in relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS), and did not require a risk evaluation and mitigation strategy on approval in the US.
Objectives:
To present the results of routine laboratory measures in the controlled treatment period of the Phase III OCR trials in RMS (OPERA I [NCT01247324]; OPERA II [NCT01412333]) and PPMS (ORATORIO [NCT01194570]).
Methods:
In the OPERA I, OPERA II and ORATORIO studies, routine safety laboratory tests, including liver function, hematology and urinalysis, were conducted at baseline and every 12 weeks until the study end. Routine safety laboratory tests were also conducted on Day 15 of the OPERA studies. At infusion visits, urine and blood samples were collected prior to the infusion of methylprednisolone. Laboratory abnormalities were defined as values outside the normal range for each specific parameter. For each laboratory test, a Marked Abnormality Range was predefined, above and/or below which a value was considered potentially clinically relevant.
Results:
The proportions of patients with potentially clinically relevant abnormalities during the controlled treatment period for the pooled OPERA (OCR N=825; interferon β-1a N=826) and ORATORIO (OCR N=486; placebo N=239) studies were:
Alkaline phosphatase: OCR 0.1%, interferon β-1a 0.4%; OCR 0.6%, placebo 0.8%;
Alanine aminotransferase: OCR 5.1%, interferon β-1a 17.7%; OCR 6.9%, placebo 7.5%;
Aspartate aminotransferase: OCR 2.2%, interferon β-1a 10.1%; OCR 2.9%, placebo 3.3%;
Glutamyl transferase: OCR 4.3%, interferon β-1a 9.1%; OCR 6.9%, placebo 4.6%;
Bilirubin: OCR 0.5%, interferon β-1a 0.1%; OCR 0.4%, placebo 1.7%;
Creatinine: OCR 0.0%, interferon β-1a 0.2%; OCR 0.2%, placebo 0.0%.
Similar trends were seen for hematology, thyroid function and electrolyte laboratory measures; these data will be presented with normal ranges.
Conclusions:
Incidence of potentially clinically relevant abnormal liver enzyme values was lower with ocrelizumab compared with interferon β-1a, and in the range observed with placebo, supporting an acceptable risk of this treatment.