Clinical Trial: Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2/3, Multicenter, Randomized, Double-blinded, Placebo-controlled, Repeat-dose Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Olipudase Alfa in Patients With

Brief Summary:

Primary Objective:

The primary objective of this phase 2/3 study is to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult patients with acid sphingomyelinase deficiency (ASMD) by assessing changes in 1) spleen volume as measured by abdominal magnetic resonance imaging (MRI) (and, for the United States [US] only, in association with patient perception related to spleen volume as measured by splenomegaly related score (SRS)); and 2) infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide (DLCO).

Secondary Objectives:

  • To confirm the safety of olipudase alfa administered intravenously once every 2 weeks for 52 weeks.
  • To characterize the effect of olipudase alfa on the patient perception related to spleen volume as measured by the SRS after 52 weeks of study drug administration. (For the US, the effect of olipudase alfa on the splenomegaly related score is part of the primary objective).
  • To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following endpoints assessed sequentially:
  • The effect of olipudase alfa on liver volume;
  • The effect of olipudase alfa on platelet count;
  • The effect of olipudase alfa on fatigue;
  • The effect of olipudase.alfa on pain;
  • The effect of olipudase alfa on dyspnea.

Detailed Summary:

The total duration per patient is at least 3 years and up to 5 years and 3 months. This includes up to approximately two month of screening, 52 weeks of primary analysis period, up to 4 years of extension treatment period, an end-of- study visit within 2 weeks of the last treatment, and a safety follow- up 30 to 37 days after the last treatment.

The study will be divided into 2 consecutive major periods: 1) a randomized placebo-controlled, double-blinded primary analysis period (PAP) from day -60 to week 52, which will be followed by 2) an extension treatment period (ETP) that will last up to 4 years and 1 month and during which all patients will receive olipudase alfa.


Sponsor: Genzyme, a Sanofi Company

Current Primary Outcome:

  • Percentage change in spleen volume (combined with change in SRS in the US only, and referred to as "combination spleen endpoint") [ Time Frame: Baseline to Week 52 ]
  • Percentage change in diffusing capacity of the lung for carbon monoxide [ Time Frame: Baseline to Week 52 ]


Original Primary Outcome: Percentage change in spleen volume [ Time Frame: Baseline to Week 52 ]

Current Secondary Outcome:

  • Change in splenomegaly-related symptom score (except US, where it is part of the primary "combination spleen endpoint") [ Time Frame: Baseline to Week 52 ]
  • Percentage change in liver volume [ Time Frame: Baseline to Week 52 ]
  • Percentage change in platelet count [ Time Frame: Baseline to Week 52 ]
  • Change in fatigue severity as measured by item 3 of the Brief Fatigue Inventory scale [ Time Frame: Baseline to Week 52 ]
  • Change in pain severity as measured by item 3 of the Brief Pain Inventory scale [ Time Frame: Baseline to Week 52 ]
  • Change in dyspnea severity as measured by the Functional Assessment of Chronic Illness Therapy dyspnea tool [ Time Frame: Baseline to Week 52 ]
  • Number of adverse events [ Time Frame: Baseline to approximately 5 years ]


Original Secondary Outcome:

  • Change in Liver Volume [ Time Frame: Baseline to Week 52 ]
  • Participants with Pulmonary imaging and function tests [ Time Frame: Baseline to Week 52 ]
  • Exercise capacity by cycle ergometry [ Time Frame: Baseline to Week 52 ]
  • Hematology [ Time Frame: Baseline to Week 52 ]
  • Physician Global Assessment [ Time Frame: Baseline to Week 52 ]
  • Efficacy biomarkers [ Time Frame: Baseline to Week 52 ]


Information By: Sanofi

Dates:
Date Received: November 26, 2013
Date Started: December 2015
Date Completion: July 2023
Last Updated: April 25, 2017
Last Verified: April 2017