Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency (ASCEND)
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).
- 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.
|Sphingomyelin Lipidosis||Drug: placebo (saline) Drug: GZ402665||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
|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 Acid Sphingomyelinase Deficiency|
- 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 ]
- 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 ]
|Study Start Date:||December 2015|
|Estimated Study Completion Date:||July 2023|
|Estimated Primary Completion Date:||July 2023 (Final data collection date for primary outcome measure)|
Olipudase alfa dose (3 mg/kg body weight) in saline administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to olipudase alfa, and during the extension treatment period for all patients.
Pharmaceutical form: Powder for concentrate for solution for infusion administered once every two weeks during the 52 weeks of the primary analysis period for patients randomized to olipudase alfa, and during the extension treatment period for all patients.
Route of administration: intravenous infusion
Other Name: olipudase alfa
Placebo Comparator: Placebo
Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to placebo.
Drug: placebo (saline)
Pharmaceutical form: solution administered once every two weeks during the 52 weeks of the primary analysis period for patients randomized to placebo.
Route of administration: intravenous infusion
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02004691
|Contact: For site information, send an email with site number to||Contact-Us@sanofi.com|
|United States, California|
|Investigational Site Number 840005||Recruiting|
|San Francisco, California, United States, 94143|
|United States, Georgia|
|Investigational Site Number 840003||Recruiting|
|Decatur, Georgia, United States, 30033|
|United States, Minnesota|
|Investigational Site Number 840004||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Investigational Site Number 036001||Recruiting|
|Westmead, Australia, 2145|
|Investigational Site Number 076001||Recruiting|
|Porto Alegre, Brazil, 90035 003|
|Investigational Site Number 152001||Recruiting|
|Santiago, Chile, 753-0204|
|Investigational Site Number 250001||Recruiting|
|Paris, France, 75020|
|Investigational Site Number 276001||Recruiting|
|Mainz, Germany, 55131|
|Investigational Site Number 380002||Recruiting|
|Napoli, Italy, 80131|
|Investigational Site Number 380001||Recruiting|
|Udine, Italy, 33100|
|Investigational Site Number 392001||Active, not recruiting|
|Investigational Site Number 528001||Recruiting|
|Amsterdam, Netherlands, 1105 AZ|
|Investigational Site Number 620001||Recruiting|
|Coimbra, Portugal, 3000-075|
|Investigational Site Number 620002||Recruiting|
|Porto, Portugal, 4099-001|
|Investigational Site Number 724001||Recruiting|
|Madrid, Spain, 28034|
|Investigational Site Number 792002||Recruiting|
|Ankara, Turkey, 06500|
|Investigational Site Number 792001||Recruiting|
|Izmir, Turkey, 35040|
|Investigational Site Number 826002||Recruiting|
|Birmingham, United Kingdom, B15 2TH|
|Investigational Site Number 826001||Recruiting|
|London, United Kingdom, WC1N 3JZ|
|Study Director:||Clinical Sciences & Operations||Sanofi|