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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02112994




Registration number
NCT02112994
Ethics application status
Date submitted
20/03/2014
Date registered
14/04/2014
Date last updated
4/12/2019

Titles & IDs
Public title
Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency
Scientific title
A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency
Secondary ID [1] 0 0
2011-004287-30
Secondary ID [2] 0 0
LAL-CL06
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lysosomal Acid Lipase Deficiency 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
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sebelipase Alfa

Experimental: Sebelipase Alfa - Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status.


Treatment: Drugs: Sebelipase Alfa
IV infusion of sebelipase alfa

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

Outcomes
Primary outcome [1] 0 0
Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) - The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.
Timepoint [1] 0 0
Screening, Week 144
Secondary outcome [1] 0 0
Percent Change In Serum Lipids From Baseline To Week 144 - The effect of sebelipase alfa on lipid metabolism was evaluated by measuring the change from baseline to Week 144 in 4 serum lipids: low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); non-HDL-C; triglycerides. Blood samples for these clinical laboratory tests were collected at scheduled time points and analyzed by a central laboratory.
Timepoint [1] 0 0
Baseline, Week 144
Secondary outcome [2] 0 0
Participants Testing Positive For Anti-drug Antibodies (ADAs) - The impact of ADAs on the safety and immunogenicity of sebelipase alfa was evaluated by testing for ADAs in participants who received sebelipase alfa in this open-label study. Blood samples for assessment were collected prior to study infusions at Week 2, Week 4, Week 8, Week 12, and every 12 weeks thereafter. Participants testing positive for ADAs were also tested for the presence of neutralizing antibodies that inhibited sebelipase alfa enzyme activity and/or cellular uptake. Any participant experiencing a moderate or severe infusion-associated reaction (IAR) was to have an additional assessment of ADAs at the next study visit (prior to study drug infusion); these participants were to also have serum samples collected at 1 to 2 hours after IAR onset and at the next study visit (prior to study drug infusion) for analysis of serum tryptase. The count of participants who became ADA positive and who tested positive for neutralizing antibodies are presented.
Timepoint [2] 0 0
Week 144
Secondary outcome [3] 0 0
Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants - To evaluate the effects of sebelipase alfa on growth parameters in pediatric participants (=18 years old) presenting with evidence of growth delay, the percent change in the anthropometric parameter of BMI-for-age percentile from Baseline to Week 144 is reported. Anthropometric parameters were plotted on standard growth curves. When possible, historical data on growth parameters was also incorporated into the analyses. Percentiles and Z-scores for BMI-for-age were determined using standard growth charts appropriate to a participant's age on the date of the assessment: the World Health Organization standard growth chart for participants =2 years of age and the Centers for Disease Control standard growth chart for participants >2 years of age.
Timepoint [3] 0 0
Baseline, Week 144
Secondary outcome [4] 0 0
Shift In Child-Pugh Status From Baseline To Week 144 - In order to evaluate the effects of sebelipase alfa on liver function, the number of participants with a shift in Child-Pugh status from Baseline to Week 144 is reported. The status is based on the Child-Pugh score, which is used in clinical practice to assess prognosis in individuals with chronic liver disease. Laboratory data were used in derivation of the score by summing individual scores (scored 1-3, with 3 indicating most severe) from clinical laboratory test results and physical examinations, including total serum bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy. The total score was used to determine the Child-Pugh status, reported as Class A (score of 5 or 6), Class B (score of 7 to 9), or Class C (score of 10 to 15). Higher scores and higher categories represented a worse outcome. Data reported as 1 of 2 types of shifts in class: No Change from Baseline; Decline from Baseline.
Timepoint [4] 0 0
Baseline, Week 144

Eligibility
Key inclusion criteria
Key

1. Participant was >8 months of age at the time of dosing.

2. Confirmation of LAL-D diagnosis as determined by the central laboratory or, for
participants with prior hematopoietic stem cell transplant or liver transplant,
historical enzyme activity or molecular genetic testing confirming a diagnosis of
LAL-D.

3. Participants >8 months but <4 years of age at Screening had at least 1 of the
following documented clinical manifestations of LAL-D:

- Dyslipidemia

- Elevated transaminases

- Impaired growth

- Suspected malabsorption

- Other clinical manifestation of LAL-D

4. Participants =4 years of age at Screening had at least 1 of the following documented
clinical manifestations of LAL-D:

- Evidence of advanced liver disease

- Histologically confirmed disease recurrence in participants with past liver or
hematopoietic transplant

- Persistent dyslipidemia

- Suspected malabsorption

- Other clinical manifestation of LAL-D

Key
Minimum age
8 Months
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participant had known causes of active liver disease other than LAL-D, which had not
been adequately treated.

2. Participant received a hematopoietic stem cell or liver transplant <2 years from the
time of dosing.

3. Participant with co-morbidities other than complications due to LAL-D, which were
irreversible or associated with a high mortality risk within 6 months or would
interfere with study compliance or data interpretation.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
NSW 2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Louisiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
Belgium
State/province [4] 0 0
Brussels
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Canada
State/province [6] 0 0
Nova Scotia
Country [7] 0 0
Croatia
State/province [7] 0 0
Zagreb
Country [8] 0 0
Denmark
State/province [8] 0 0
Copenhagen
Country [9] 0 0
Germany
State/province [9] 0 0
Freiburg
Country [10] 0 0
Italy
State/province [10] 0 0
Padova
Country [11] 0 0
Mexico
State/province [11] 0 0
Mexico City
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Russian Federation
State/province [13] 0 0
Moscow
Country [14] 0 0
Spain
State/province [14] 0 0
A Coruna
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
Turkey
State/province [17] 0 0
Balcali
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study evaluated the safety and efficacy of sebelipase alfa in a broad population of
participants with lysosomal acid lipase deficiency (LAL-D).
Trial website
https://clinicaltrials.gov/show/NCT02112994
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Summary results
Other publications