Page last updated: August 13, 2026
Page reviewed by: Dr. Cara O’Neill, FAAP
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Trial Summary
“JR-446 is a novel drug developed based on the J-Brain Cargo technology, which has been clinically validated through the approval of IZCARGO for the treatment of MPS II in Japan in 2021. Animal studies have previously confirmed delivery of JR-446 into the Central Nervous System (CNS) and somatic organs and significant reduction of substrate caused by the deficiency in the enzyme that causative for the onset of MPS IIIB. As there is no established standard of care for the treatment of MPS IIIB, JR-446 is believed to have the potential to become a transformative treatment of MPS IIIB,” according to JCR.
JCR’s proprietary J-Brain Cargo technology involves the fusion of enzyme to a transferrin receptor targeting antibody. Transferrin receptors are abundant on the surface of blood vessels that supply brain tissue. The combined enzyme-antibody fusion protein can engage with the transferrin receptor to allow the needed enzyme to cross the blood brain barrier and gain entry into the central nervous system.
A graphic representation of the J-brain cargo technology
Trial Details
*Important note: There are two separate clinical trials for JR-446. Each has different study status, locations, and inclusion and exclusion criteria. Please read carefully to distinguish between the two.
Clinical Trial of JR-446 (Japan)
Study title: An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB (Trial in Japan)
Trial listing: Read the clinical trial in Japan’s information on ClinicalTrials.gov for more details including contact information to reach out to the study sites, full inclusion and exclusion criteria. We encourage you to check the ClinicalTrials.gov link frequently for updates on possible new study sites and changes in enrollment status or criteria.
Study status: Recruiting
Number of participants: 10 patients (estimated) with Type B
Duration: Up to 4 years
Locations:
- Hiroshima University Hospital, Hiroshima, Japan
- University of the Ryukyus Hospital, Okinawa, Japan
- National Center for Child Health and Development, Tokyo, Japan
Qualifications to Participate:
Inclusion Criteria:
- Chronological age of <18 years
- Confirmed diagnosis of MPS IIIB
Exclusion Criteria:
- Prior experience to gene therapy or HSCT with successful engraftment
- Past use of another investigational drug or product in last 4 months or 5 half-lives (whichever is longer) before signing ICF
- Current participation in a clinical trial or past participation (within 30 days of enrolment into this study) in a study involving invasive procedures
- Past use of Genistein or Kineret (anakinra) within 4 months before signing ICF
- Serious drug allergy or hypersensitivity
- Contraindication for lumbar puncture or MRI
- History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following lumbar puncture
Clinical Trial of JR-446 (U.S., Germany, and United Kingdom)
Study title: and A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB) (Trial in U.S., Germany, and United Kingdom)
Trial listing: Read the clinical trial in the U.S., U.K., and Germany’s information on ClinicalTrials.gov for more details including contact information to reach out to the study sites, full inclusion and exclusion criteria. We encourage you to check the ClinicalTrials.gov link frequently for updates on possible new study sites and changes in enrollment status or criteria.
Study status: Some sites are enrolling
Number of participants: 12 patients (estimated) with Type B
Duration: 1 year
Locations:
- Children’s Hospital Oakland Research Institution/UCSF Oakland, Oakland, CA, U.S. – Now enrolling
- UPMC Children’s Hospital of Pittsburgh, Pittsburg, PA, U.S. – Not yet enrolling
- Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, PA, U.S. – Not yet enrolling
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany – Not yet enrolling
- Great Ormond Street Hospital for Children, London, United Kingdom – Not yet enrolling
Qualifications to Participate:
Inclusion Criteria:
- Patients with confirmed MPS IIIB with a phenotype of MPS IIIB that is not classified as slowly progressive (i.e., not attenuated).
- A chronological age <6 years.
- Ability to complete and achieve a Standard score ≥55, using either Bailey Scale of Infant Development-4 (BSID-4) Cognitive domain or Kaufman Assessment Battery for Children-II (KABC-II) Non-Verbal Index, whichever tool is most appropriate for the participant’s chronological age.
Exclusion Criteria:
- Contraindication for lumbar puncture or MRI.
- A participant who has a medical condition or extenuating circumstance that, in the opinion of the principal investigator or sub-investigator, might compromise the participant’s ability to comply with protocol requirements, the participant’s well-being or safety, or the interpretability of the participant’s clinical data.
- A participant who has received any other investigational drug product (including but not limited to, tralesinidase alfa enzyme replacement therapy [TA-ERT], Genistein, KINERET [anakinra], ambroxol, miglustat) within 4 months (or 5 half-lives, whichever is longer) before the time of providing informed consent.
- A participant who has received gene therapy treatment or hematopoietic stem cell transplantation (HSCT) with successful engraftment.
- Serious drug allergy or hypersensitivity to any components of JR-446 or medications likely prescribed during the trial.
- A participant has a history of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following lumbar puncture.
- A patient with recurrent epileptic seizures not adequately controlled with anti-seizure medication, and which, in the clinical judgment of the principal investigator, would preclude safe participation in the trial.
- Serology consistent with human immunodeficiency virus (HIV) exposure or consistent with active hepatitis B (HepB) or hepatitis C (HepC) infection.
- A participant/family, who, in the opinion of the investigator, may not be able to comply with protocol requirements and cooperate fully with the trial assessments, procedures, and scheduling for JR-446 IMP dose administrations.
- Study participants for whom informed consent is unable to be provided by a parent or legal guardian; or when applicable for a study participant who is unable to provide assent with respect to study participation in conjunction with parental or legal guardian consent for participation on study.
Trial Updates
June 2026
JCR Pharmaceuticals’ JR-446 enzyme replacement therapy (ERT) for Sanfilippo Syndrome Type B is listed on ClinicalTrials.gov for a trial in the U.S., Germany, and United Kingdom. Please review the listing to learn about specific trial locations and enrollment status. There are three locations listed in the U.S. In addition to the sites, the listing includes this trial’s inclusion and exclusion criteria. Access the U.S. and European listing for JR-446 on ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07640984
September 2025
The Ministry of Health, Labour and Welfare of Japan has granted orphan drug designation to JR-446, an investigational drug for the treatment of mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo syndrome type B). JR-446 was granted orphan drug designation for the treatment of MPS IIIB by the U.S. Food and Drug Administration (FDA) in April 2025,1 and by the European Commission (EC) in June 2025. Read more.
June 2025
JR-446 for the treatment of MPS IIIB has been granted the Orphan Drug Designation (ODD) from the European Commission, following the ODD received from the US FDA in May. Read the statement.
May 2025
MEDIPAL and JCR Pharmaceuticals Co., Ltd. announced on May 9, 2025, that the U.S. Food and Drug Administration granted orphan drug designation to the JR-446 investigational drug for the treatment of mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo syndrome type B). Read the statement.
February 2025
MEDIPAL participated in the 21st Annual WORLDSymposium. In addition to taking in the presentations, especially those regarding the field of gene therapy, MEDIPAL leaders hosted several meetings with others in attendance, including Cure Sanfilippo Foundation.
“Our meeting with the Cure Sanfilippo Foundation facilitated a productive exchange of perspectives on global trends and approaches in drug development, and newborn screening in the United States. This discussion provided us with invaluable insights for future global development,” stated MEDIPAL in a web article. Read the complete article.
December 2024
MEDIPAL and JCR Pharmaceuticals announce “initiation of
the Phase I/II clinical trial of JR-446 in Japan following the dosing of the first individual from the trial. JR-446 is a proprietary blood-brain barrier (BBB)-penetrating α-N-acetylglucosaminidase in development for the treatment of mucopolysaccharidosis type IIIB (Sanfilippo syndrome type B or MPS IIIB).” Read the announcement.
July 4, 2024
“An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB” is listed on ClinicalTrials.gov. The listing includes inclusion and exclusion criteria, as well as the locations of the three trials sites and their contact information. Read the listing.
July 1, 2024
MEDIPAL and JCR Pharmaceuticals announced the completion of the regulatory review by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) for the clinical trial notification for the phase I/II study of JR-446, a blood-brain barrier-penetrating α-N-acetylglucosaminidase, for the treatment of mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome type B). The company plans to start the clinical trial in Japan in the coming months (April-September 2024). Read more.
September 2023
MEDIPAL Holdings Corporation and JCR Pharmaceuticals announced that the Board of Directors of both companies have reached agreement on their partnership to develop JR-446, a blood-brain barrier (BBB) penetrating form of α-N-acetylglucosaminidase that was developed using JCR’s proprietary J-Brain Cargo® technology, for the treatment of Mucopolysaccharidosis Type IIIB (MPS IIIB or Sanfilippo syndrome type B).
Under the ex-Japan licensing agreement, MEDIPAL will acquire an exclusive commercialization right of JR-446 with sublicensing rights, including clinical development, manufacturing, and marketing. As regards to the Japan collaboration agreement, MEDIPAL will support RegardingJCR in the clinical development of JR-446 in Japan, including distribution of investigational drugs, disease awareness and conducting clinical trials. Read more.