Mucopolysaccharidosis IIIPhase 1/2NCT04018755
Open-label Study of Anakinra in MPS III
A Phase 1/2 study testing anakinra in people with Mucopolysaccharidosis III, run by Lynda E Polgreen at 1 site in United States.
Trial summary
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disorder of metabolism, associated with insufficient production of a lysosomal enzyme needed for normal cell function. As a consequence of the cellular dysfunction, patients with this disorder develop progressive, irreversible neurodegeneration. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Mucopolysaccharidosis III
- What is being tested?
- anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2020to 8 Mar 2023
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- MPS III
- ≥ 4 years of age
- Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided when cognitively possible.
- If on Genistein, must have been on a stable dose for 6 months prior to enrollment
- If on melatonin or other sleep medications, must have been on stable doses for the past 3 months
Who cannot join
- Currently enrolled in another ongoing clinical treatment trial
- Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.
- Use of the following therapies prior to enrollment:
- Narcotic analgesics within 24 hours prior to enrollment.
- Tocilizumab, dapsone or mycophenolate mofetil within 3 weeks prior to enrollment.
- Etanercept, leflunomide, thalidomide, or cyclosporine or intraarticular, intramuscular, intravenous, or oral administration of glucocorticoids within 4 weeks prior to enrollment.
Show all 23Show fewer
- Intravenous immunoglobulin (IVIG), adalimumab, or methotrexate within 8 weeks prior to enrollment.
- Infliximab, 6-mercaptopurine, azathioprine, cyclophosphamide or chlorambucil within 12 weeks prior to enrollment.
- Rituximab within 26 weeks prior to enrollment
- Live vaccines within 1 month prior to enrollment.
- Known presence or suspicion of active, chronic or recurrent serious bacterial, fungal or viral infections, including tuberculosis, HIV infection or hepatitis B or C infection.
- Clinical evidence of liver disease or liver injury as indicated by presence of abnormal liver tests:
- AST or ALT > 5 x ULN, or
- AST or ALT > 3 x ULN accompanied by elevated bilirubin >2 x ULN.
- Presence of severe renal function impairment (estimated creatinine clearance < 30 mL/min/1.73m2).
- Presence of neutropenia.
- History of malignancy.
- Known hypersensitivity to E coli-derived proteins, or any components of Kineret® (anakinra).
- Pregnant or lactating women.
- Current active infection;
- History of serious opportunistic infection (e.g., bacterial [Legionella and Listeria]; tuberculosis [TB]; invasive fungal infections; or viral, parasitic, and other opportunistic infections);
- Positive TB skin test, positive Quantiferon-TB Gold TB test, positive chest X-ray, or a recent exposure to TB
- Requirement for live vaccine exposure that would be expected to occur during the time frame of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
The Lundquist Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: Open-label Pilot Study of the Effects of Anakinra in Mucopolysaccharidosis (MPS) III
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disorder of metabolism, associated with insufficient production of a lysosomal enzyme needed for normal cell function. As a consequence of the cellular dysfunction, patients with this disorder develop progressive, irreversible neurodegeneration. Sadly, to date no evidence-based treatments are available.
Inflammation has been connected with disease pathogenesis in the MPS disorders. Therapies aimed at decreasing inflammation are currently being studied in many MPS disorders and benefits in both brain and other parts of the body have been reported.Decreasing interleukin-1 (IL-1) in an animal model of MPS III showed benefits in brain disease and behavior. Thus, we think that anakinra (Kineret), which decreases IL-1 levels in the body, will improve behavioral and other problems in children with MPS III.
Read more
Anakinra is approved by the FDA for treatment of rheumatoid arthritis (RA) and neonatal-onset multisystem inflammatory disease (NOMID). It is not approved for any MPS disorder.
The design of this study is an open-label, single center, pilot study of 20 participants with MPS III. There will be an initial screening visit, followed by an 8-week observational period, then a 36-week treatment period, and finally another 8-week observational period to determine any effects of withdrawal from the treatment.
During visits the participants will undergo a medical history, a physical examination, and anthropometric measurements. Blood, urine, and stool will be collected for biomarker levels and safety laboratory studies. Questionnaires will be completed with questions related to behavior, stooling, sleep, and activities of daily living. Seizure and movement disorders will be monitored as well.
The most common risks of receiving anakinra, based on RA and NOMID experience, include local injection site reactions, headache, nausea, vomiting, arthralgia, and flu-like symptoms. The most serious potential risk is a serious infection and neutropenia. However, because so few people with MPS have been treated with anakinra, all the risks related to MPS patients receiving anakinra are not currently known. Additional risks related to taking part in the study include some pain, bruising, and/or bleeding due to blood draws/peripheral IV placement, and discomfort with completing some of the questionnaires.
The expected potential direct benefits include, but are not limited to, improved behavior, sleep, stooling, communication, mood, and gait; as well as decreased seizure frequency, disordered movement and fatigue. However, there is no guarantee that participants will get any benefit from being in this study.
- Conditions
- Mucopolysaccharidosis III
- Being tested
- anakinra
- Medical subject headings
- Mucopolysaccharidosis III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anakinraBiological
Also called Kineret
anakinra single-use prefilled glass syringes
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | anakinra 100 mg subcutaneous once daily Receives: Biological: anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percent of participants who required an increase in anakinra dose from 100 mg SC daily to 200 mg SC daily at Week 8 or Week 16
Need for dose escalation was determined by within individual change over an 8-week treatment period compared to change over the 8-week pre-treatment observational period in the 2 most bothersome symptoms for each enrolled patient chosen by their caregiver and selected from 6 suverys included in the Multi-domian Responder Index (MDRI). These surveys were:
- Sanfilippo Behavior Rating Scale (SBRS)
- Child Sleep Health Questionnaire (CSHQ)
- Autism Parenting Stress Index (APSI)
- PROMIS Fatigue - Parent Proxy Custom Short Form
- Movement disorder - parent reported frequency, duration, and severity (7-day log)
- Non-communicating Children's Pain Checklist-Revised (NCCPC-R)
Measured: up to 8 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start30 Jan 2020
- Primary completion17 Jul 2022
- Study completion8 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis IIIStudies 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lynda E Polgreen
- Sponsor type
- University, hospital or other
- Collaborators
- Cure Sanfilippo Foundation, Swedish Orphan Biovitrum
- Responsible party
- Sponsor-investigator, Lynda E Polgreen, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Investigators
- Lynda Polgreen, MD, MS, Principal investigator, The Lundquist Institute at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04018755
- Sponsor's protocol ID
- 31834-01
- Status last verified
- Oct 2024
- First submitted
- 1 Jul 2019
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Polgreen LE, Chen AH, Pak Y, Luzzi A, Morales Garval A, Acevedo J, Bitan G, Iacovino M, O'Neill C, Eisengart JB. Anakinra in Sanfilippo syndrome: a phase 1/2 trial. Nat Med. 2024 Sep;30(9):2473-2479. doi: 10.1038/s41591-024-03079-3. Epub 2024 Jun 21.
PubMed 38907160
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Pilot Study of the Effects of Anakinra in Mucopolysaccharidosis (MPS) III
- ClinicalTrials.gov ID
- NCT04018755
- Acronym / sponsor ID
- 31834-01
- Conditions
- Mucopolysaccharidosis III
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Lynda E PolgreenUniversity, hospital or other
- Collaborators
- Cure Sanfilippo Foundation, Swedish Orphan Biovitrum
- Study start
- 30 Jan 2020 (actual)
- Primary completion
- 17 Jul 2022 (actual)
- Study completion
- 8 Mar 2023 (actual)
- First posted
- 12 Jul 2019 (actual)
- 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.
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disorder of metabolism, associated with insufficient production of a lysosomal enzyme needed for normal cell function. As a consequence of the cellular dysfunction, patients with this disorder develop progressive, irreversible neurodegeneration. Sadly, to date no evidence-based treatments are available.
Inflammation has been connected with disease pathogenesis in the MPS disorders. Therapies aimed at decreasing inflammation are currently being studied in many MPS disorders and benefits in both brain and other parts of the body have been reported.Decreasing interleukin-1 (IL-1) in an animal model of MPS III showed benefits in brain disease and behavior. Thus, we think that anakinra (Kineret), which decreases IL-1 levels in the body, will improve behavioral and other problems in children with MPS III.
Anakinra is approved by the FDA for treatment of rheumatoid arthritis (RA) and neonatal-onset multisystem inflammatory disease (NOMID). It is not approved for any MPS disorder.
The design of this study is an open-label, single center, pilot study of 20 participants with MPS III. There will be an initial screening visit, followed by an 8-week observational period, then a 36-week treatment period, and finally another 8-week observational period to determine any effects of withdrawal from the treatment.
During visits the participants will undergo a medical history, a physical examination, and anthropometric measurements. Blood, urine, and stool will be collected for biomarker levels and safety laboratory studies. Questionnaires will be completed with questions related to behavior, stooling, sleep, and activities of daily living. Seizure and movement disorders will be monitored as well.
The most common risks of receiving anakinra, based on RA and NOMID experience, include local injection site reactions, headache, nausea, vomiting, arthralgia, and flu-like symptoms. The most serious potential risk is a serious infection and neutropenia. However, because so few people with MPS have been treated with anakinra, all the risks related to MPS patients receiving anakinra are not currently known. Additional risks related to taking part in the study include some pain, bruising, and/or bleeding due to blood draws/peripheral IV placement, and discomfort with completing some of the questionnaires.
The expected potential direct benefits include, but are not limited to, improved behavior, sleep, stooling, communication, mood, and gait; as well as decreased seizure frequency, disordered movement and fatigue. However, there is no guarantee that participants will get any benefit from being in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Biological: anakinraanakinra 100 mg subcutaneous once daily |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- MPS III
- ≥ 4 years of age
- Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided when cognitively possible.
- If on Genistein, must have been on a stable dose for 6 months prior to enrollment
- If on melatonin or other sleep medications, must have been on stable doses for the past 3 months
Key exclusion criteria (23 listed)
- Currently enrolled in another ongoing clinical treatment trial
- Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.
- Use of the following therapies prior to enrollment:
- Live vaccines within 1 month prior to enrollment.
- Known presence or suspicion of active, chronic or recurrent serious bacterial, fungal or viral infections, including tuberculosis, HIV infection or hepatitis B or C infection.
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 |
|---|---|---|
| anakinraAlso: Kineretanakinra single-use prefilled glass syringes | Biological | treatment |
Primary outcome
The percent of participants who required an increase in anakinra dose from 100 mg SC daily to 200 mg SC daily at Week 8 or Week 16
Time frame: up to 8 weeks of treatment
Need for dose escalation was determined by within individual change over an 8-week treatment period compared to change over the 8-week pre-treatment observational period in the 2 most bothersome symptoms for each enrolled patient chosen by their caregiver and selected from 6 suverys included in the Multi-domian Responder Index (MDRI). These surveys were: * Sanfilippo Behavior Rating Scale (SBRS) * Child Sleep Health Questionnaire (CSHQ) * Autism Parenting Stress Index (APSI) * PROMIS Fatigue - Parent Proxy Custom Short Form * Movement disorder - parent reported frequency, duration, and severity (7-day log) * Non-communicating Children's Pain Checklist-Revised (NCCPC-R)
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 22 Oct 2024.
- Derived from this study: PubMed 38907160Polgreen LE, Chen AH, Pak Y, Luzzi A, Morales Garval A, Acevedo J, Bitan G, Iacovino M, O'Neill C, Eisengart JB. Anakinra in Sanfilippo syndrome: a phase 1/2 trial. Nat Med. 2024 Sep;30(9):2473-2479. doi: 10.1038/s41591-024-03079-3. Epub 2024 Jun 21.
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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.
Lynda Polgreen, MD, MS principal investigator
The Lundquist Institute at Harbor-UCLA Medical Center
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 anakinra in people with Mucopolysaccharidosis III, run by Lynda E Polgreen 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 23 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 22 Oct 2024. 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 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?
The percent of participants who required an increase in anakinra dose from 100 mg SC daily to 200 mg SC daily at Week 8 or Week 16 (time frame: up to 8 weeks of treatment). 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 NCT04018755, which also lists 1 linked publication.
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 22 Oct 2024.