Human Acid Sphingomyelinase DeficiencyPhase 1NCT01722526
Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients
A Phase 1 study testing Recombinant human acid sphingomyelinase in people with Human Acid Sphingomyelinase Deficiency, run by Genzyme, a Sanofi Company at 2 sites in 2 countries.
Trial summary
To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose administration. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Acid Sphingomyelinase Deficiency
- What is being tested?
- Recombinant human acid sphingomyelinase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Mar 2013to Jan 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with documented non-neuronopathic acid sphingomyelinase deficiency
- The patient has a diffusing capacity of carbon monoxide (DLco) >20% and ≤80% of the predicted normal value.
- The patient has a spleen volume ≥6 multiples of normal(MN). A partial splenectomy will be permitted if performed ≥1 year prior to Screening/Baseline and residual spleen volume is ≥6 MN.
- The patient who is receiving lipid lowering therapy should be on a stable dose and regimen of lipid-lowering therapy(ies) for at least 12 weeks prior to Screening/Baseline, with the patient expected to remain on the same dose and regimen throughout the 26-week treatment period.
- The patient who is female and of childbearing potential must have a negative serum pregnancy test for β-HCG.
Who cannot join
- The patient is female and pregnant or lactating.
- The patient has a Body Mass Index(BMI)>30.
- The patient has received an investigational drug within 30 days prior to study enrollment
- The patient has a medical condition or any extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
- The patient has had a major organ transplant
- ALT or AST >250 IU/L or total bilirubin >1.5 mg/dL.
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- The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior to and 3 days after each rhASM infusion for the duration of the study.
- The patient requires medications that may decrease rhASM
- The patient is unwilling or unable to avoid the use of medications or herbal supplements that may cause or prolong bleeding, or have potential hepatotoxicity within 10 days prior to and 3 days after liver biopsy
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: An Open-label, Multicenter, Ascending Dose Study of the Tolerability and Safety of Recombinant Human Acid Sphingomyelinase (rhASM) in Patients With Acid Sphingomyelinase Deficiency (ASMD)
To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose administration.
- Conditions
- Human Acid Sphingomyelinase Deficiency
- Being tested
- Recombinant human acid sphingomyelinase
- Keywords
- Human acid sphingomyelinase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human acid sphingomyelinaseDrug
Also called GZ402665
Administered intravenously every 2 weeks for 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| Recombinant human acid sphingomyelinase | Experimental | Participants will receive rhASM of an initial dose of 0.1 mg/kg, followed by several dose escalations, as tolerated, up to 3.0 mg/kg. All doses are given 2 weeks apart. Receives: Drug: Recombinant human acid sphingomyelinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of Adverse Events (AEs)
Measured: at least 26 weeks
Secondary outcomes (2)
Pharmacokinetics as measured by peak plasma concentration (Cmax), time to peak concentration (tmax), area under curve (AUC), half life (t1/2), drug clearance (CL), and volume of distribution (Vss)
Measured: up to 26 weeks
Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot
Measured: up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study startMar 2013
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Human Acid Sphingomyelinase DeficiencyStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01722526
- Sponsor's protocol ID
- DFI13412
- Other IDs
- 2012-003542-32, SPHINGO00812
- Status last verified
- Jul 2015
- First submitted
- 5 Nov 2012
- Last updated
- 30 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Thurberg BL, Diaz GA, Lachmann RH, Schiano T, Wasserstein MP, Ji AJ, Zaher A, Peterschmitt MJ. Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment. Mol Genet Metab. 2020 Sep-Oct;131(1-2):245-252. doi: 10.1016/j.ymgme.2020.06.010. Epub 2020 Jun 24.
PubMed 32620536Thurberg BL, Wasserstein MP, Jones SA, Schiano TD, Cox GF, Puga AC. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency. Am J Surg Pathol. 2016 Sep;40(9):1232-42. doi: 10.1097/PAS.0000000000000659.
PubMed 27340749Wasserstein MP, Jones SA, Soran H, Diaz GA, Lippa N, Thurberg BL, Culm-Merdek K, Shamiyeh E, Inguilizian H, Cox GF, Puga AC. Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency. Mol Genet Metab. 2015 Sep-Oct;116(1-2):88-97. doi: 10.1016/j.ymgme.2015.05.013. Epub 2015 May 30.
PubMed 26049896
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Ascending Dose Study of the Tolerability and Safety of Recombinant Human Acid Sphingomyelinase (rhASM) in Patients With Acid Sphingomyelinase Deficiency (ASMD)
- ClinicalTrials.gov ID
- NCT01722526
- Acronym / sponsor ID
- DFI13412
- Conditions
- Human Acid Sphingomyelinase Deficiency
- Keywords
- Human acid sphingomyelinase deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Mar 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 7 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant human acid sphingomyelinase | Experimental | Drug: Recombinant human acid sphingomyelinaseParticipants will receive rhASM of an initial dose of 0.1 mg/kg, followed by several dose escalations, as tolerated, up to 3.0 mg/kg. All doses are given 2 weeks apart. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with documented non-neuronopathic acid sphingomyelinase deficiency
- The patient has a diffusing capacity of carbon monoxide (DLco) >20% and ≤80% of the predicted normal value.
- The patient has a spleen volume ≥6 multiples of normal(MN). A partial splenectomy will be permitted if performed ≥1 year prior to Screening/Baseline and residual spleen volume is ≥6 MN.
- The patient who is receiving lipid lowering therapy should be on a stable dose and regimen of lipid-lowering therapy(ies) for at least 12 weeks prior to Screening/Baseline, with the patient expected to remain on the same dose and regimen throughout the 26-week treatment period.
- The patient who is female and of childbearing potential must have a negative serum pregnancy test for β-HCG.
Key exclusion criteria (9 listed)
- The patient is female and pregnant or lactating.
- The patient has a Body Mass Index(BMI)>30.
- The patient has received an investigational drug within 30 days prior to study enrollment
- The patient has a medical condition or any extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
- The patient has had a major organ transplant
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 |
|---|---|---|
| Recombinant human acid sphingomyelinaseAlso: GZ402665Administered intravenously every 2 weeks for 26 weeks | Drug | Recombinant human acid sphingomyelinase |
Primary outcome
Summary of Adverse Events (AEs)
Time frame: at least 26 weeks
2 secondary outcomes
Pharmacokinetics as measured by peak plasma concentration (Cmax), time to peak concentration (tmax), area under curve (AUC), half life (t1/2), drug clearance (CL), and volume of distribution (Vss)
Time frame: up to 26 weeks
Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot
Time frame: up to 26 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2015.
- Derived from this study: PubMed 32620536Thurberg BL, Diaz GA, Lachmann RH, Schiano T, Wasserstein MP, Ji AJ, Zaher A, Peterschmitt MJ. Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment. Mol Genet Metab. 2020 Sep-Oct;131(1-2):245-252. doi: 10.1016/j.ymgme.2020.06.010. Epub 2020 Jun 24.
- Derived from this study: PubMed 27340749Thurberg BL, Wasserstein MP, Jones SA, Schiano TD, Cox GF, Puga AC. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency. Am J Surg Pathol. 2016 Sep;40(9):1232-42. doi: 10.1097/PAS.0000000000000659.
- Derived from this study: PubMed 26049896Wasserstein MP, Jones SA, Soran H, Diaz GA, Lippa N, Thurberg BL, Culm-Merdek K, Shamiyeh E, Inguilizian H, Cox GF, Puga AC. Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency. Mol Genet Metab. 2015 Sep-Oct;116(1-2):88-97. doi: 10.1016/j.ymgme.2015.05.013. Epub 2015 May 30.
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.
Medical Monitor study director
Genzyme, a Sanofi Company
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant human acid sphingomyelinase in people with Human Acid Sphingomyelinase Deficiency, run by Genzyme, a Sanofi Company at 2 sites in 2 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 5 inclusion and 9 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 30 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Summary of Adverse Events (AEs) (time frame: at least 26 weeks). 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 NCT01722526, which also lists 3 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 30 Jul 2015.