CompletedPhase 1/2

Open-label Study of Anakinra in MPS III

United States24 participantsStarted 2020-01-30

Plain-language 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. 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.

Who can participate

Age range

4 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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 Exclusion Criteria: * 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. * 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 di…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

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

Timeframe: up to 8 weeks of treatment

Trial details

NCT IDNCT04018755

SponsorLynda E Polgreen

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2022-07-17

View on ClinicalTrials.gov More Mucopolysaccharidosis III trials