NCT04018755

Open-label Study of Anakinra in MPS III

Completed Phase 1, PHASE2 Last updated 22 October 2024

What this trial tests

Phase 1, PHASE2 trial testing anakinra in Mucopolysaccharidosis III in 24 participants. Completed in 8 March 2023.

Timeline

30 January 2020

Primary endpoint
17 July 2022

8 March 2023

Quick facts

Lead sponsor	Lynda E Polgreen
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	24
Start date	30 January 2020
Primary completion	17 July 2022
Estimated completion	8 March 2023
Sites	1 location across United States

Drugs / interventions tested

• anakinra (ANAKINRA) — full drug profile →

Conditions studied

• Mucopolysaccharidosis III — all drugs for Mucopolysaccharidosis III →

Sponsor

Lynda E Polgreen

Who can join

4 and older, any sex, with Mucopolysaccharidosis III. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Novel therapies for mucopolysaccharidosis type III.
   Seker Yilmaz B, Davison J, Jones SA, Baruteau J. · · 2021 · cited 39× · PMID 32944950 · DOI 10.1002/jimd.12316
2. Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets.
   Leal AF, Benincore-Flórez E, Rintz E, Herreño-Pachón AM, et al · · 2022 · cited 35× · PMID 36613919 · DOI 10.3390/ijms24010477
3. The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy.
   Wiesinger AM, Bigger B, Giugliani R, Scarpa M, et al · · 2022 · cited 20× · PMID 35645812 · DOI 10.3389/fphar.2022.863667
4. Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.
   Ago Y, Rintz E, Musini KS, Ma Z, et al · · 2024 · cited 18× · PMID 38256186 · DOI 10.3390/ijms25021113
5. Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.
   Pan X, Taherzadeh M, Bose P, Heon-Roberts R, et al · · 2022 · cited 18× · PMID 35704026 · DOI 10.1084/jem.20211860
6. An Engineered <i>sgsh</i> Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA.
   Douek AM, Amiri Khabooshan M, Henry J, Stamatis SA, et al · · 2021 · cited 12× · PMID 34073041 · DOI 10.3390/ijms22115948
7. Anakinra in Sanfilippo syndrome: a phase 1/2 trial.
   Polgreen LE, Chen AH, Pak Y, Luzzi A, et al · · 2024 · cited 5× · PMID 38907160 · DOI 10.1038/s41591-024-03079-3
8. Is the eye a window to the brain in Sanfilippo syndrome?
   Beard H, Chidlow G, Neumann D, Nazri N, et al · · 2020 · cited 5× · PMID 33203474 · DOI 10.1186/s40478-020-01070-w