Acid Sphingomyelinase DeficiencyPhase 1NCT00410566
Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)
A Phase 1 study testing rhASM in people with Acid Sphingomyelinase Deficiency and Niemann-Pick Disease, run by Genzyme, a Sanofi Company at 1 site in United States.
Trial summary
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acid Sphingomyelinase Deficiency, Niemann-Pick Disease
- What is being tested?
- rhASM
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Apr 2009
- 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
- Signed, informed consent by the patient or legal guardian prior to performing any study-related procedures;
- Have ≤ 0.2 nmol/hr/mg protein ASM activity in peripheral leukocytes, as measured by the reference laboratory;
- Have a diffusing capacity (DLco) > 30% of the predicted normal value;
- Have a spleen volume ≥ 2x normal
- Female patients of childbearing potential must have a serum pregnancy test negative for β-hCG and agree to use a reliable birth control method for the duration of the study.
Who cannot join
- Is pregnant or lactating;
- Has received an investigational drug within 30 days prior to study enrollment;
- Has a medical condition, including serious intercurrent illness, active hepatitis B or C or human immunodeficiency virus (HIV) infection, cirrhosis, > stage 3 liver fibrosis, INR >1.5, platelet count < 60.0x10^3/µL, significant cardiac disease (e.g. pulmonary artery pressure > 40 mm Hg, moderate or severe valvular dysfunction, or < 40% left ventricular ejection fraction by echocardiography (ECHO)), or any other extenuating circumstances that may significantly interfere with study compliance including all prescribed evaluations and follow-up activities;
- Has had a major organ transplant (e.g. bone marrow or liver);
- Has had a total splenectomy;
- Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >250 IU/L or a total bilirubin >3.6 mg/dL;
- Is unwilling or unable to avoid the use of alcohol, medications that may decrease rhASM activity, medications or herbal supplements that may cause or prolong bleeding, and the use of medications or herbal supplements with potential hepatoxicity within 14 days prior to and 28 days afte the rhASM infusion.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single-Center, Single Dose, Dose Escalation Study of Recombinant Human Acid Sphingomyelinase (rhASM) in Adults With Acid Sphingomyelinase Deficiency (ASMD)
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.
Read the detailed description
ASM deficiency (ASMD), also known as Niemann-Pick A and B disease, is a rare genetic disorder in which reduced activity of the lysosomal enzyme, ASM, leads to the accumulation of sphingomyelin primarily in macrophages throughout the body. This deficiency results in characteristic features such as hepatosplenomegaly, thrombocytopenia, interstitial lung disease, growth retardation, coronary artery disease, fatigue, and in severe cases, neurodegeneration with death in early childhood. There is no specific treatment for this disease. This Phase 1 safety study will seek to enroll a minimum of 12 and a maximum of 30 eligible adults patients with ASMD with each patient participating for approximately 7 weeks.
- Being tested
- rhASM
- Keywords
- Acid sphingomyelinase deficiency, Niemann-Pick disease, Lysosomal storage disorder, Enzyme replacement therapy, Treatment
- Medical subject headings
- Niemann-Pick Diseases, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhASMDrug
Single dose of 0.03mg/kg body weight IV
rhASMDrug
Single dose of 0.1mg/kg body weight IV
rhASMDrug
Single dose of 0.3mg/kg body weight IV
rhASMDrug
Single dose of 0.6mg/kg body weight IV
rhASMDrug
Single dose of 1.0mg/kg body weight IV
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: rhASM |
| 2 | Experimental | Not described Receives: Drug: rhASM |
| 3 | Experimental | Not described Receives: Drug: rhASM |
| 4 | Experimental | Not described Receives: Drug: rhASM |
| 5 | Experimental | Not described Receives: Drug: rhASM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessments via physical exam,AE reporting,telemetry heartrate monitoring,ECG,ECHO,clinical lab evaluations,liver and adrenal function tests,cytokine testing,adrenal hormone levels,lipid profile,chest Xrays,liver biopsies,MRI of internal
Measured: Pre-, During-, and Post-infusion (up to 72 hrs); 14 day and 28 day follow-up visit
Immune Response Measure
Measured: Pre-infusion and final visit (Day 28)
Secondary outcomes (1)
PK measurements
Measured: Pre- and Post-infusion up to 72 hrs.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionMar 2009
- Study completionApr 2009
Why it stopped: Terminated by sponsor - Single dose safety objective achieved.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT00410566
- Sponsor's protocol ID
- SPHINGO00605
- Status last verified
- Mar 2015
- First submitted
- 11 Dec 2006
- Last updated
- 19 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single-Center, Single Dose, Dose Escalation Study of Recombinant Human Acid Sphingomyelinase (rhASM) in Adults With Acid Sphingomyelinase Deficiency (ASMD)
- ClinicalTrials.gov ID
- NCT00410566
- Acronym / sponsor ID
- SPHINGO00605
- Keywords
- Acid sphingomyelinase deficiency, Niemann-Pick disease, Lysosomal storage disorder, Enzyme replacement therapy, Treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated by sponsor - Single dose safety objective achieved.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 13 Dec 2006 (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.
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.
Detailed description
ASM deficiency (ASMD), also known as Niemann-Pick A and B disease, is a rare genetic disorder in which reduced activity of the lysosomal enzyme, ASM, leads to the accumulation of sphingomyelin primarily in macrophages throughout the body. This deficiency results in characteristic features such as hepatosplenomegaly, thrombocytopenia, interstitial lung disease, growth retardation, coronary artery disease, fatigue, and in severe cases, neurodegeneration with death in early childhood. There is no specific treatment for this disease. This Phase 1 safety study will seek to enroll a minimum of 12 and a maximum of 30 eligible adults patients with ASMD with each patient participating for approximately 7 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rhASM |
| 2 | Experimental | Drug: rhASM |
| 3 | Experimental | Drug: rhASM |
| 4 | Experimental | Drug: rhASM |
| 5 | Experimental | Drug: rhASM |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Signed, informed consent by the patient or legal guardian prior to performing any study-related procedures;
- Have ≤ 0.2 nmol/hr/mg protein ASM activity in peripheral leukocytes, as measured by the reference laboratory;
- Have a diffusing capacity (DLco) > 30% of the predicted normal value;
- Have a spleen volume ≥ 2x normal
- Female patients of childbearing potential must have a serum pregnancy test negative for β-hCG and agree to use a reliable birth control method for the duration of the study.
Key exclusion criteria (7 listed)
- Is pregnant or lactating;
- Has received an investigational drug within 30 days prior to study enrollment;
- Has a medical condition, including serious intercurrent illness, active hepatitis B or C or human immunodeficiency virus (HIV) infection, cirrhosis, > stage 3 liver fibrosis, INR >1.5, platelet count < 60.0x10^3/µL, significant cardiac disease (e.g. pulmonary artery pressure > 40 mm Hg, moderate or severe valvular dysfunction, or < 40% left ventricular ejection fraction by echocardiography (ECHO)), or any other extenuating circumstances that may significantly interfere with study compliance including all prescribed evaluations and follow-up activities;
- Has had a major organ transplant (e.g. bone marrow or liver);
- Has had a total splenectomy;
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 |
|---|---|---|
| rhASMSingle dose of 0.03mg/kg body weight IV | Drug | 1 |
| rhASMSingle dose of 0.1mg/kg body weight IV | Drug | 2 |
| rhASMSingle dose of 0.3mg/kg body weight IV | Drug | 3 |
| rhASMSingle dose of 0.6mg/kg body weight IV | Drug | 4 |
| rhASMSingle dose of 1.0mg/kg body weight IV | Drug | 5 |
Primary outcome
Safety assessments via physical exam,AE reporting,telemetry heartrate monitoring,ECG,ECHO,clinical lab evaluations,liver and adrenal function tests,cytokine testing,adrenal hormone levels,lipid profile,chest Xrays,liver biopsies,MRI of internal
Time frame: Pre-, During-, and Post-infusion (up to 72 hrs); 14 day and 28 day follow-up visit
Immune Response Measure
Time frame: Pre-infusion and final visit (Day 28)
1 secondary outcome
PK measurements
Time frame: Pre- and Post-infusion up to 72 hrs.
Results and safety
The study was stopped early (reason given: Terminated by sponsor - Single dose safety objective achieved.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2015.
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rhASM in people with Acid Sphingomyelinase Deficiency and Niemann-Pick Disease, run by Genzyme, a Sanofi Company at 1 site in United States.
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 7 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: stopped early, as of the sponsor's last update on 19 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was stopped early (reason given: Terminated by sponsor - Single dose safety objective achieved.). Results are not available in the source record.
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?
Safety assessments via physical exam,AE reporting,telemetry heartrate monitoring,ECG,ECHO,clinical lab evaluations,liver and adrenal function tests,cytokine testing,adrenal hormone levels,lipid profile,chest Xrays,liver biopsies,MRI of internal (time frame: Pre-, During-, and Post-infusion (up to 72 hrs); 14 day and 28 day follow-up visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Mar 2015.