Hurler Syndrome (MPS I)Phase 1/2NCT01372228
Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
A Phase 1/2 study testing hematopoietic stem cell infusion in people with Hurler Syndrome (MPS I) and Hurler-Scheie Syndrome, run by Talaris Therapeutics Inc. at 1 site in United States.
Trial summary
The goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hurler Syndrome (MPS I), Hurler-Scheie Syndrome, Hunter Syndrome (MPS II)
- What is being tested?
- hematopoietic stem cell infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Apr 2016
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a confirmed diagnosis of inherited metabolic disorder / inborn error of metabolism. Diagnosis should be confirmed by appropriate test(s) (enzyme and/or mutation analysis) before study entry. Patients must not be eligible for myeloablative chemotherapy as a preparative regimen for transplant due to age, co-morbidities or organ dysfunction.
- Inborn errors of metabolism / Inherited Metabolic Disorders (IMD) eligible for this study include the following:
- Hurler Syndrome (MPS I)
- Hurler-Scheie Syndrome with early neurologic involvement and/or sensitization to ERT
- Hunter Syndrome (MPS II)
- Sanfilippo Syndrome (MPS III)
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- Krabbe Disease (Globoid Leukodystrophy)
- Metachromatic Leukodystrophy (MLD)
- Adrenoleukodystrophy (ALD and AMN)
- Sandhoff Disease
- Tay Sachs Disease
- Pelizaeus Merzbacher (PMD)
- Niemann-Pick Disease
- Alpha-mannosidosis
- Patients must have adequate function of other organ systems as measured by:
- Creatinine less than or equal to 2.0 mg/dl and creatinine clearance ≥60 cc/min/1.73m2. Newborns must have a creatinine clearance ≥ 25 cc/min. For babies less than or equal to 3 months of age, the raw value on glomerular filtration rate (GFR) must be ≥ 1 cc/kg/min.
- Hepatic transaminases (ALT/AST) 2.5 x normal, bilirubin <2.0mg/dl
- Normal cardiac function by echocardiogram or radionuclide scan (ejection fraction or shortening fraction >80% of normal value for age)
- Pulmonary function tests (PFTs) demonstrating forced expiratory volume at one second (FEV1) of ≥50% of predicted for age. If child is too young or unable to perform PFTs, crying vital capacity result of >50% of normal value for age or resting pulse oximeter >92% on room air or clearance by pulmonologist will be required.
- Patient must have a related donor (identical or mismatched for 1, 2 or 3 Human Leukocyte Antigen (HLA)-A, -B or -DR loci).
- Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines.
- Patients must have a minimum life expectancy of at least 6 months.
- Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).
- There is no upper or lower age limit for this study.
Who cannot join
- Patients with uncontrolled seizures, apnea, evidence of recurrent or uncontrolled aspiration, or need for chronic mechanical ventilation.
- Patients with allogeneic stem cell transplant with cytoreductive therapy in the past 6 months.
- Subjects must not have had previous radiation therapy that would preclude total body irradiation (TBI) (as determined by radiation therapist)
- Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate reduced intensity transplantation.
- Subjects with a positive human immunodeficiency virus (HIV) antibody test result
- Subjects who are pregnant, as indicated by a positive serum human chorionic gonadotropin (HCG) test
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- Subjects whose only donor is pregnant at the time of intended transplant
- Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site
- Jehovah's witnesses being unwilling to be transfused
- Patients that have any comorbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.
- Lack of related donors
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
The goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders.
Read the detailed description
The objective for the study is to establish chimerism following reduced intensity conditioning with no grade III/IV GVHD. The primary endpoint we will follow is production of the missing enzyme at ≥ 10% of the normal level at day 180 post-transplant in > 90% of patients.
- Conditions
- Hurler Syndrome (MPS I), Hurler-Scheie Syndrome, Hunter Syndrome (MPS II), Sanfilippo Syndrome (MPS III), Krabbe Disease (Globoid Leukodystrophy), Metachromatic Leukodystrophy (MLD)
- Being tested
- hematopoietic stem cell infusion
- Keywords
- hematopoietic stem cell Tx, chimerism, leukodystrophy
- Medical subject headings
- Mucopolysaccharidosis I, Mucopolysaccharidosis II, Sudden Infant Death, Mucopolysaccharidosis III, Leukodystrophy, Globoid Cell, Leukodystrophy, Metachromatic, Adrenoleukodystrophy, Sandhoff Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hematopoietic stem cell infusionBiological
Enriched hematopoetic stem cell infusion
| Study group | Role | What they receive |
|---|---|---|
| Inherited Metabolic Disorder Patients | Experimental | Recipients are treated with hematopoietic stem cell infusion from living donors Receives: Biological: hematopoietic stem cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Production of missing enzyme at levels greater than or equal to 10% of normal
Measured: Day 180 post transplant to three years
Secondary outcomes (1)
Enriched Hematopoetic Stem Cell Engraftment
Measured: One month to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2011 (estimated)
- Study startApr 2011
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: company did not pursue this indication
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hurler Syndrome (MPS I)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Talaris Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Duke University
- Responsible party
- Sponsor
- Investigators
- Suzanne T Ildstad, MD, Study director, Talaris Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01372228
- Sponsor's protocol ID
- ICT-14070-010611
- Status last verified
- Apr 2023
- First submitted
- 10 Jun 2011
- Last updated
- 12 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
- ClinicalTrials.gov ID
- NCT01372228
- Acronym / sponsor ID
- ICT-14070-010611
- Conditions
- Hurler Syndrome (MPS I), Hurler-Scheie Syndrome, Hunter Syndrome (MPS II), Sanfilippo Syndrome (MPS III), Krabbe Disease (Globoid Leukodystrophy), Metachromatic Leukodystrophy (MLD)
- Keywords
- hematopoietic stem cell Tx, chimerism, leukodystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: company did not pursue this indication
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Talaris Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Duke University
- Study start
- Apr 2011 (actual)
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 13 Jun 2011 (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 goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders.
Detailed description
The objective for the study is to establish chimerism following reduced intensity conditioning with no grade III/IV GVHD. The primary endpoint we will follow is production of the missing enzyme at ≥ 10% of the normal level at day 180 post-transplant in > 90% of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Inherited Metabolic Disorder Patients | Experimental | Biological: hematopoietic stem cell infusionRecipients are treated with hematopoietic stem cell infusion from living donors |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Patients must have a confirmed diagnosis of inherited metabolic disorder / inborn error of metabolism. Diagnosis should be confirmed by appropriate test(s) (enzyme and/or mutation analysis) before study entry. Patients must not be eligible for myeloablative chemotherapy as a preparative regimen for transplant due to age, co-morbidities or organ dysfunction.
- Inborn errors of metabolism / Inherited Metabolic Disorders (IMD) eligible for this study include the following:
- Patients must have adequate function of other organ systems as measured by:
- Patient must have a related donor (identical or mismatched for 1, 2 or 3 Human Leukocyte Antigen (HLA)-A, -B or -DR loci).
- Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines.
Key exclusion criteria (11 listed)
- Patients with uncontrolled seizures, apnea, evidence of recurrent or uncontrolled aspiration, or need for chronic mechanical ventilation.
- Patients with allogeneic stem cell transplant with cytoreductive therapy in the past 6 months.
- Subjects must not have had previous radiation therapy that would preclude total body irradiation (TBI) (as determined by radiation therapist)
- Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate reduced intensity transplantation.
- Subjects with a positive human immunodeficiency virus (HIV) antibody test result
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 |
|---|---|---|
| hematopoietic stem cell infusionEnriched hematopoetic stem cell infusion | Biological | Inherited Metabolic Disorder Patients |
Primary outcome
Production of missing enzyme at levels greater than or equal to 10% of normal
Time frame: Day 180 post transplant to three years
1 secondary outcome
Enriched Hematopoetic Stem Cell Engraftment
Time frame: One month to three years
Results and safety
The study was stopped early (reason given: company did not pursue this indication). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Hurler Syndrome (MPS I)
Active, not recruitingObservational study
Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.
Hematopoietic Cell Transplantation, Mucopolysaccharidosis Type I
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
RecruitingPhase 1
ISP-001: Sleeping Beauty Transposon-Engineered B Cells for MPS I
Mucopolysaccharidosis IH/S, Mucopolysaccharidosis IS
Active, not recruitingPhase 1/2
Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant
Mucopolysaccharidosis IH
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.
Suzanne T Ildstad, MD study director
Talaris Therapeutics Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing hematopoietic stem cell infusion in people with Hurler Syndrome (MPS I) and Hurler-Scheie Syndrome, run by Talaris Therapeutics Inc. 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 24 inclusion and 11 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 12 Apr 2023. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: company did not pursue this indication). 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?
Production of missing enzyme at levels greater than or equal to 10% of normal (time frame: Day 180 post transplant to three years). 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 12 Apr 2023.