Sphingomyelin LipidosisPhase 2/3ASCENDNCT02004691
Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
A Phase 2/3 study testing Olipudase alfa in people with Sphingomyelin Lipidosis, run by Genzyme, a Sanofi Company at 24 sites in 17 countries.
Trial summary
Primary Objective: The primary objective of this phase 2/3 study was to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult participants with acid sphingomyelinase deficiency (ASMD) by assessing changes in: 1) spleen… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sphingomyelin Lipidosis
- What is being tested?
- Olipudase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 24 sitesin 17 countries
- Study dates
- 18 Dec 2015to 19 Oct 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The participant was willing and able to provide signed written informed consent.
- The participant was male or female aged 18 years or older.
- The participant had documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; and a clinical diagnosis consistent with Niemann-Pick disease type B (NPD B).
- The participant had diffuse capacity of the lung for carbon monoxide less than or equal to (<=)70% of the predicted normal value.
- The participant had a spleen volume greater than or equal to (>=)6 multiples of normal (MN) measured by MRI; participant who have had partial splenectomy was allowed if the procedure was performed >=1 year before screening/baseline and the residual spleen volume was >=6 MN.
- The participant had an SRS >=5.
- Female participants of childbearing potential must have had a negative serum pregnancy test for beta-human chorionic gonadotropin (β-HCG).
- Female participants of childbearing potential and male participants were willing to practice true abstinence in line with their preferred and usual lifestyle, or use 2 acceptable effective methods of contraception for up to 15 days following their last dose of study drug.
Who cannot join
- The participant had received an investigational drug within 30 days before study enrollment.
- The participant had a medical condition, including significant intercurrent illness; significant cardiac disease (e.g., clinically significant arrhythmia, moderate or severe pulmonary hypertension or clinically significant valve dysfunction, or less than or equal to (<=)40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); malignancy diagnosed within the past 5 years (other than non-melanoma skin cancer), or any other serious medical condition that might have precluded participation in the study.
- The participant had a platelet count less than (<)60,000/microliters based on the average of 2 samples.
- The participant had an international normalized ratio (INR) greater than (>)1.5.
- The participant had alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL (except for participant with Gilbert's syndrome).
- The participant had a major organ transplant (eg, bone marrow or liver).
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- The participant was scheduled during the study for in-patient hospitalization including elective surgery and excluding the liver biopsies required per protocol.
- The participant, in the opinion of the investigator, was unable to adhere to the requirements of the study.
- The participant was unwilling or unable to abstain from the use of alcohol for 1 day before and 3 days after each study drug infusion. Testing for blood alcohol levels was not required.
- The participant was unwilling or unable to avoid 10 days before and 3 days after the protocol scheduled liver biopsies the use of medications or herbal supplements that were potentially hepatotoxic (e.g., 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, anti-depressants, kava, echinacea) and/or might have caused or prolonged bleeding (e.g., anti-coagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng).
- The participant required medications that might have decreased olipudase alfa activity (e.g., fluoxetine, chlorpromazine, tricyclic antidepressants [e.g., imipramine, or desipramine]).
- The participant required use of invasive ventilatory support.
- The participant required use of noninvasive ventilator support while awake for longer than 12 hours daily.
- The participant was breast-feeding.
- The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
24 sites in 17 countries.
24 sites in 17 countries
Turkey (Türkiye)4 sites
Investigational Site Number : 792002
Ankara, 06500
Investigational Site Number : 792004
Istanbul, 34520
Investigational Site Number : 792003
Istanbul, 34722
Investigational Site Number : 792001
Izmir, 35040
United States3 sites
Emory University Site Number : 840003
Decatur, Georgia, 30033
UCSF Medical Center Site Number : 840005
San Francisco, California, 94143
Montefiore Medical Center Site Number : 840006
The Bronx, New York, 10467
Italy2 sites
Investigational Site Number : 380002
Naples, 80131
Investigational Site Number : 380001
Udine, 33100
United Kingdom2 sites
Investigational Site Number : 826002
Birmingham, B15 2GW
Investigational Site Number : 826001
London, London, City of, WC1N 3JZ
Australia1 site
Investigational Site Number : 036001
Westmead, New South Wales, 2145
Brazil1 site
Hospital De Clinicas De Porto Alegre Site Number : 076001
Porto Alegre, Rio Grande do Sul, 90035 003
Chile1 site
Investigational Site Number : 152001
Santiago, Reg Metropolitana de Santiago, 753-0204
About this study
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
Primary Objective:
The primary objective of this phase 2/3 study was to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult participants 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 participant 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).
Read more
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 participant 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 SRS is part of the primary objective).
- To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following outcome measures 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.
Read the detailed description
The planned total duration per participant was for at least 3 years and up to 5 years and 3 months. This included up to approximately two month of screening, 52 weeks of primary analysis period, up to 4 years and 3 months 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.
- Conditions
- Sphingomyelin Lipidosis
- Being tested
- placebo (saline), Olipudase alfa
- Medical subject headings
- Niemann-Pick Disease, Type A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placebo (saline)Drug
Pharmaceutical form: solution administered once every two weeks during the 52 weeks of the primary analysis period for participants randomized to placebo.
Route of administration: intravenous infusion
Olipudase alfaDrug
Also called GZ402665, Xenpozyme™
Pharmaceutical form: Powder for concentrate for solution for infusion administered once every two weeks during the 52 weeks of the primary analysis period for participants randomized to olipudase alfa, and during the extension treatment period for all participants.
Route of administration: intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to placebo. Receives: Drug: placebo (saline) |
| Olipudase alfa | Experimental | 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. Receives: Drug: Olipudase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Baseline
Percent predicted Hb and Altitude-adjusted DLco was calculated as: 100*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) times Hemoglobin-adjusted factor times Altitude-adjustment factor.
Measured: Baseline (Day 1)
Percent Change From Baseline in Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Week 52
Percent predicted Hb and Altitude-adjusted DLco was calculated as: 100*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) times Hemoglobin-adjusted factor times Altitude-adjustment factor.
Measured: Baseline, Week 52
Combination Spleen Endpoint: Component 1: Spleen Volume (in MN) at Baseline
Spleen volume was assessed by abdominal magnetic resonance imaging (MRI) to quantitate the degree of splenomegaly in multiples of normal (MN).
Measured: Baseline (Day 1)
Combination Spleen Endpoint: Component 1: Percent Change From Baseline in Spleen Volume (in MN) at Week 52
Spleen volume was assessed by abdominal MRI to quantitate the degree of splenomegaly in MN.
Measured: Baseline, Week 52
Combination Spleen Endpoint (Primary for US Only): Component 2: Splenomegaly-Related Score (SRS) at Baseline
The SRS rates 5 items: abdominal pain, abdominal discomfort, early satiety, dissatisfaction with abdominal body image, and difficulty to bend down using a numerical rating scale of 0 (absent) to 10 (worst imaginable). The total score of SRS ranges from 0 to 50, with higher scores (50) indicated worst imaginable rating. It was pre-specified as secondary endpoint for countries outside of US.
Measured: Baseline (Day 1)
Combination Spleen Endpoint (Primary for US Only): Component 2: Change From Baseline in Splenomegaly-Related Score (SRS) at Week 52
The SRS rates 5 items: abdominal pain, abdominal discomfort, early satiety, dissatisfaction with abdominal body image, and difficulty to bend down using a numerical rating scale of 0 (absent) to 10 (worst imaginable). The total score of SRS ranges from 0 to 50, with higher scores (50) indicated worst imaginable rating. It was pre-specified as secondary endpoint for countries outside of US.
Measured: Baseline, Week 52
Secondary outcomes (9)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) up to Week 52
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Reported AEs are treatment-emergent AEs that developed, worsened or became serious during the treatment period.
Measured: From the first infusion of investigational medicinal product (IMP) up to 52 weeks
Number of Participants With Adverse Events of Special Interest (AESIs) up to Week 52
An AESI was defined as an AE (serious or nonserious) of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor was appropriate. AESIs included any pregnancy, symptomatic overdose, dose-limiting toxicities (DLTs) as defined in protocol and infusion associated reactions (IARs). Protocol-defined IARs were AEs that occurred during the infusion or within up to 24 hours after the start of infusion and were considered as related or possibly related to the study treatment by the investigator or the sponsor. Events occurring greater than or equal to (>=) 24 hours after the start of an infusion might have been judged an IAR at the discretion of the investigator or sponsor. Algorithm-defined IARs were all AEs that started between the start of infusion and the end of infusion plus 24 hours, irrespective of the perceived relation with study treatment.
Measured: From the first infusion of IMP up to 52 weeks
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Liver Function Tests up to Week 52
PCSA criteria: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): >3 x upper limit of normal (ULN), >5 x ULN, >10 x ULN and >20 x ULN. Alkaline phosphatase (ALP) > 1.5 x ULN. Total bilirubin >1.5 x ULN and >2 x ULN. ALT and total bilirubin: ALT > 3 x ULN and total bilirubin > 2 x ULN. Baseline was defined as the last non-missing value prior to the first infusion of study treatment.
Measured: From Baseline (Day 1) up to 52 weeks
Number of Participants Who Developed Anti-Drug Antibodies (ADA) to Olipudase Alfa up to Week 52
Number of participants with treatment-emergent ADA are presented. Baseline was defined as the last non-missing value prior to the first infusion of study treatment.
Measured: Baseline (Day 1) and Week 52
Percent Change From Baseline in Liver Volume (in MN) at Week 52
Liver volume was assessed by abdominal MRI in MN.
Measured: Baseline, Week 52
Percent Change From Baseline in Platelet Counts at Week 52
Measured: Baseline, Week 52
Change From Baseline in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI)-Item 3 Scale Score at Week 52
The BFI is a 9-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 9-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to "Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. Numerical rating scale ranges from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue.
Measured: Baseline, Week 52
Change From Baseline in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score at Week 52
The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a numeric rating scale to assess pain severity and pain interference in the past 24 hours and the past week. For BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The numeric rating scale ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain.
Measured: Baseline, Week 52
Change From Baseline in Dyspnea Severity as Measured by Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnea Scale at Week 52
FACIT-Dyspnea is a 20 Item assessment that is split into two 10-item sections. The first 10-item section asks participants about the severity of their shortness of breath during various activities. The second 10-item section asks participants to rate the difficulty due to shortness of breath associated with the same activities that were referenced in the first section. For the dyspnea severity items, score range from 0=no shortness of breath; 1=mildly short of breath; 2=moderately short of breath; 3=severely short of breath. For the functional limitation items, score range from no difficult = 0, A little difficult = 1, some difficult = 2, and much difficulty =3. A raw score was calculated as: sum of individual item scores * 10/number of items answered. Raw scores were then converted to scale scores using the table included in the FACIT Dyspnea Scale Short Form Scoring Guideline. FACIT dyspnea scale score ranged between 27.7 to 75.9. Higher score represented high levels of dyspnea.
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2013 (estimated)
- Study start18 Dec 2015
- Primary completion15 Mar 2021
- Study completion19 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sphingomyelin LipidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02004691
- Sponsor's protocol ID
- DFI12712
- Other IDs
- U1111-1142-5963, DFI12712, 2015-000371-26, 2015
- Acronym
- ASCEND
- Status last verified
- Oct 2024
- First submitted
- 26 Nov 2013
- Last updated
- 7 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.
- Expanded access
- Available
Publications
Mistry PK, Cassiman D, Jones SA, Lachmann R, Lukina E, Prada CE, Wasserstein MP, Thurberg BL, Foster MC, Patel RM, Underhill LH, Peterschmitt MJ. Acid sphingomyelinase deficiency and Gaucher disease: Underdiagnosed and often treatable causes of hepatomegaly, splenomegaly, and low HDL cholesterol in lean individuals. Hepatol Commun. 2025 Jan 7;9(1):e0621. doi: 10.1097/HC9.0000000000000621. eCollection 2025 Jan 1.
PubMed 39774103Wasserstein MP, Lachmann R, Hollak C, Barbato A, Gallagher RC, Giugliani R, Guelbert NB, Hennermann JB, Ikezoe T, Lidove O, Mabe P, Mengel E, Scarpa M, Senates E, Tchan M, Villarrubia J, Thurberg BL, Yarramaneni A, Armstrong NM, Kim Y, Kumar M. Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial. Orphanet J Rare Dis. 2023 Dec 2;18(1):378. doi: 10.1186/s13023-023-02983-0.
PubMed 38042851
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02004691
- Acronym / sponsor ID
- ASCEND / DFI12712
- Conditions
- Sphingomyelin Lipidosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2015 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 19 Oct 2023 (actual)
- First posted
- 9 Dec 2013 (estimated)
- Results
- Posted 24 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
The primary objective of this phase 2/3 study was to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult participants 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 participant 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 participant 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 SRS is part of the primary objective).
- To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following outcome measures 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 description
The planned total duration per participant was for at least 3 years and up to 5 years and 3 months. This included up to approximately two month of screening, 52 weeks of primary analysis period, up to 4 years and 3 months 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: placebo (saline)Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to placebo. |
| Olipudase alfa | Experimental | Drug: Olipudase alfaOlipudase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The participant was willing and able to provide signed written informed consent.
- The participant was male or female aged 18 years or older.
- The participant had documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; and a clinical diagnosis consistent with Niemann-Pick disease type B (NPD B).
- The participant had diffuse capacity of the lung for carbon monoxide less than or equal to (<=)70% of the predicted normal value.
- The participant had a spleen volume greater than or equal to (>=)6 multiples of normal (MN) measured by MRI; participant who have had partial splenectomy was allowed if the procedure was performed >=1 year before screening/baseline and the residual spleen volume was >=6 MN.
Key exclusion criteria (15 listed)
- The participant had received an investigational drug within 30 days before study enrollment.
- The participant had a medical condition, including significant intercurrent illness; significant cardiac disease (e.g., clinically significant arrhythmia, moderate or severe pulmonary hypertension or clinically significant valve dysfunction, or less than or equal to (<=)40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); malignancy diagnosed within the past 5 years (other than non-melanoma skin cancer), or any other serious medical condition that might have precluded participation in the study.
- The participant had a platelet count less than (<)60,000/microliters based on the average of 2 samples.
- The participant had an international normalized ratio (INR) greater than (>)1.5.
- The participant had alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL (except for participant with Gilbert's syndrome).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placebo (saline)Pharmaceutical form: solution administered once every two weeks during the 52 weeks of the primary analysis period for participants randomized to placebo. Route of administration: intravenous infusion | Drug | Placebo |
| Olipudase alfaAlso: GZ402665, Xenpozyme™Pharmaceutical form: Powder for concentrate for solution for infusion administered once every two weeks during the 52 weeks of the primary analysis period for participants randomized to olipudase alfa, and during the extension treatment period for all participants. Route of administration: intravenous infusion | Drug | Olipudase alfa |
Primary outcome
Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Baseline
Time frame: Baseline (Day 1)
Percent predicted Hb and Altitude-adjusted DLco was calculated as: 100*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) times Hemoglobin-adjusted factor times Altitude-adjustment factor.
Percent Change From Baseline in Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Week 52
Time frame: Baseline, Week 52
Percent predicted Hb and Altitude-adjusted DLco was calculated as: 100*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) times Hemoglobin-adjusted factor times Altitude-adjustment factor.
Combination Spleen Endpoint: Component 1: Spleen Volume (in MN) at Baseline
Time frame: Baseline (Day 1)
Spleen volume was assessed by abdominal magnetic resonance imaging (MRI) to quantitate the degree of splenomegaly in multiples of normal (MN).
Combination Spleen Endpoint: Component 1: Percent Change From Baseline in Spleen Volume (in MN) at Week 52
Time frame: Baseline, Week 52
Spleen volume was assessed by abdominal MRI to quantitate the degree of splenomegaly in MN.
Combination Spleen Endpoint (Primary for US Only): Component 2: Splenomegaly-Related Score (SRS) at Baseline
Time frame: Baseline (Day 1)
The SRS rates 5 items: abdominal pain, abdominal discomfort, early satiety, dissatisfaction with abdominal body image, and difficulty to bend down using a numerical rating scale of 0 (absent) to 10 (worst imaginable). The total score of SRS ranges from 0 to 50, with higher scores (50) indicated worst imaginable rating. It was pre-specified as secondary endpoint for countries outside of US.
Combination Spleen Endpoint (Primary for US Only): Component 2: Change From Baseline in Splenomegaly-Related Score (SRS) at Week 52
Time frame: Baseline, Week 52
The SRS rates 5 items: abdominal pain, abdominal discomfort, early satiety, dissatisfaction with abdominal body image, and difficulty to bend down using a numerical rating scale of 0 (absent) to 10 (worst imaginable). The total score of SRS ranges from 0 to 50, with higher scores (50) indicated worst imaginable rating. It was pre-specified as secondary endpoint for countries outside of US.
9 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) up to Week 52
Time frame: From the first infusion of investigational medicinal product (IMP) up to 52 weeks
Number of Participants With Adverse Events of Special Interest (AESIs) up to Week 52
Time frame: From the first infusion of IMP up to 52 weeks
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Liver Function Tests up to Week 52
Time frame: From Baseline (Day 1) up to 52 weeks
Number of Participants Who Developed Anti-Drug Antibodies (ADA) to Olipudase Alfa up to Week 52
Time frame: Baseline (Day 1) and Week 52
Percent Change From Baseline in Liver Volume (in MN) at Week 52
Time frame: Baseline, Week 52
Percent Change From Baseline in Platelet Counts at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI)-Item 3 Scale Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Dyspnea Severity as Measured by Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnea Scale at Week 52
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39774103Mistry PK, Cassiman D, Jones SA, Lachmann R, Lukina E, Prada CE, Wasserstein MP, Thurberg BL, Foster MC, Patel RM, Underhill LH, Peterschmitt MJ. Acid sphingomyelinase deficiency and Gaucher disease: Underdiagnosed and often treatable causes of hepatomegaly, splenomegaly, and low HDL cholesterol in lean individuals. Hepatol Commun. 2025 Jan 7;9(1):e0621. doi: 10.1097/HC9.0000000000000621. eCollection 2025 Jan 1.
- Derived from this study: PubMed 38042851Wasserstein MP, Lachmann R, Hollak C, Barbato A, Gallagher RC, Giugliani R, Guelbert NB, Hennermann JB, Ikezoe T, Lidove O, Mabe P, Mengel E, Scarpa M, Senates E, Tchan M, Villarrubia J, Thurberg BL, Yarramaneni A, Armstrong NM, Kim Y, Kumar M. Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial. Orphanet J Rare Dis. 2023 Dec 2;18(1):378. doi: 10.1186/s13023-023-02983-0.
- A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: One-year results, Genetics in Medicine, 2022,ISSN 1098-3600Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
24 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Olipudase alfa in people with Sphingomyelin Lipidosis, run by Genzyme, a Sanofi Company at 24 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Turkey (Türkiye), United States, Italy, United Kingdom, Argentina and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Baseline (time frame: Baseline (Day 1)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02004691, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.