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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02004691




Registration number
NCT02004691
Ethics application status
Date submitted
26/11/2013
Date registered
9/12/2013
Date last updated
4/12/2023

Titles & IDs
Public title
Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
Scientific 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
Secondary ID [1] 0 0
U1111-1142-5963
Secondary ID [2] 0 0
DFI12712
Universal Trial Number (UTN)
Trial acronym
ASCEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sphingomyelin Lipidosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - placebo (saline)
Treatment: Drugs - GZ402665

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.

Experimental: GZ402665 - 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.


Treatment: Drugs: 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

Treatment: Drugs: GZ402665
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Baseline
Timepoint [1] 0 0
Baseline (Day 1)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline, Week 52
Primary outcome [3] 0 0
Combination Spleen Endpoint: Component 1: Spleen Volume (in MN) at Baseline
Timepoint [3] 0 0
Baseline (Day 1)
Primary outcome [4] 0 0
Combination Spleen Endpoint: Component 1: Percent Change From Baseline in Spleen Volume (in MN) at Week 52
Timepoint [4] 0 0
Baseline, Week 52
Primary outcome [5] 0 0
Combination Spleen Endpoint (Primary for US Only): Component 2: Splenomegaly-Related Score (SRS) at Baseline
Timepoint [5] 0 0
Baseline (Day 1)
Primary outcome [6] 0 0
Combination Spleen Endpoint (Primary for US Only): Component 2: Change From Baseline in Splenomegaly-Related Score (SRS) at Week 52
Timepoint [6] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Percent Change From Baseline in Liver Volume (in MN) at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Percent Change From Baseline in Platelet Counts at Week 52
Timepoint [2] 0 0
Baseline, Week 52
Secondary outcome [3] 0 0
Change From Baseline in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI)-Item 3 Scale Score at Week 52
Timepoint [3] 0 0
Baseline, Week 52
Secondary outcome [4] 0 0
Change From Baseline in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score at Week 52
Timepoint [4] 0 0
Baseline, Week 52
Secondary outcome [5] 0 0
Change From Baseline in Dyspnea Severity as Measured by Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnea Scale at Week 52
Timepoint [5] 0 0
Baseline, Week 52

Eligibility
Key inclusion criteria
Inclusion criteria :

- The participant is willing and able to provide signed written informed consent.

- The participant is male or female aged 18 years or older.

- The participant has 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 has diffuse capacity of the lung for carbon monoxide less than or
equal to (<=)70% of the predicted normal value.

- The participant has a spleen volume greater than or equal to (>=)6 multiples of normal
(MN) measured by MRI; participant who have had partial splenectomy will be allowed if
the procedure was performed >=1 year before screening/baseline and the residual spleen
volume is >=6 MN.

- The participant has an SRS >=5.

- Female participants of childbearing potential must have a negative serum pregnancy
test for beta-human chorionic gonadotropin (ß-HCG).

- Female participants of childbearing potential and male participants must be 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- The participant has received an investigational drug within 30 days before study
enrollment.

- The participant has 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 may preclude participation in the study.

- The participant has a platelet count less than (<)60,000/microliters based on the
average of 2 samples.

- The participant has an international normalized ratio (INR) greater than (>)1.5.

- The participant has 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 has had a major organ transplant (eg, bone marrow or liver).

- The participant is 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, is unable to adhere to the
requirements of the study.

- The participant is 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
will not be required.

- The participant is 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
are potentially hepatotoxic (e.g., 3-hydroxy-3-methyl glutaryl coenzyme A reductase
inhibitors, erythromycin, valproic acid, anti-depressants, kava, echinacea) and/or may
cause or prolong bleeding (e.g., anti-coagulants, ibuprofen, aspirin, garlic
supplements, ginkgo, ginseng).

- The participant requires medications that may decrease olipudase alfa activity (e.g.,
fluoxetine, chlorpromazine, tricyclic antidepressants [e.g., imipramine, or
desipramine]).

- The participant requires use of invasive ventilatory support.

- The participant requires use of noninvasive ventilator support while awake for longer
than 12 hours daily.

- The participant is breast-feeding.

The above information is not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/10/2023
Sample size
Target
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Investigational Site Number : 036001 - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
Argentina
State/province [4] 0 0
Córdoba
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Brazil
State/province [6] 0 0
Rio Grande Do Sul
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Sofia
Country [8] 0 0
Chile
State/province [8] 0 0
Reg Metropolitana De Santiago
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
Germany
State/province [10] 0 0
Mainz
Country [11] 0 0
Italy
State/province [11] 0 0
Napoli
Country [12] 0 0
Italy
State/province [12] 0 0
Udine
Country [13] 0 0
Japan
State/province [13] 0 0
Fukushima
Country [14] 0 0
Netherlands
State/province [14] 0 0
Amsterdam
Country [15] 0 0
Portugal
State/province [15] 0 0
Porto
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
Tunisia
State/province [17] 0 0
Tunis
Country [18] 0 0
Turkey
State/province [18] 0 0
Ankara
Country [19] 0 0
Turkey
State/province [19] 0 0
Istanbul
Country [20] 0 0
Turkey
State/province [20] 0 0
Izmir
Country [21] 0 0
United Kingdom
State/province [21] 0 0
London, City Of
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genzyme, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02004691
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries