First-in-human Study of UX016 in GNEM

A Phase 1/2, First-in-human, Double-blind, Placebo-controlled Study to Assess Dose, Safety, and Efficacy of UX016 (Sialic Acid-C16 Prodrug) in Adults With GNE Myopathy

The goal of this study is to assess the safety and dose of UX016 and its impact on muscle strength in adults with GNE Myopathy (GNEM).

Study Overview

• Status: Recruiting
• Conditions: GNE Myopathy
• Intervention / Treatment: Drug: UX016; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Patient Contact: Trial Recruitment; Phone Number: 1-888-756-8657; Email: TrialRecruitment@ultragenyx.com
• Study Contact Backup: Name: HCP Contact: Medical Information; Phone Number: 1-888-756-8657; Email: medinfo@ultragenyx.com

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Not yet recruiting
      • Clinical Trial Site
  • New Jersey
    • Iselin, New Jersey, United States, 08830
      • Recruiting
      • Rare Disease Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A confirmed diagnosis of GNEM (also known as distal myopathy with rimmed vacuoles [DMRV], hereditary inclusion body myopathy [HIBM], inclusion body myopathy 2 [IBM2], and Nonaka myopathy in Japan) by Clinical Laboratory Improvement Amendments (CLIA)-certified genetic testing with identification of a disease-associated variant in the gene encoding the GNE/MNK enzyme. Genotyping will not be conducted in this protocol
• Ability to walk a minimum of 20 m independently during Screening. The use of assistive devices and orthotics is allowed.
• Has ≤ 80% of normal biceps strength (dominant side) assessed by hand-held dynamometry (HHD) associated with a clinical pattern of weakening in the upper extremity and ability to provide reproducible force in unilateral elbow flexors (dominant side) during HHD testing (unilateral between test variability of ≤ 15%) during Screening.
• Willing and able to comply with all study procedures including needle muscle biopsies of the quadriceps muscle.
• From informed consent to after the last dose of study drug, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant and willing to have additional pregnancy testing during the study. Females considered not of childbearing potential include those who have been in menopause for at least 2 years, have had tubal ligation at least 1 year prior to Screening, or who have had a total hysterectomy. If male, agree not to father a child or donate sperm.
• Provide informed consent after the nature of the study has been explained and prior to any research-related procedures.

Exclusion Criteria:

• Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites, including 6-sialyllactose; intravenous immune globulin; supplements; or anything that can be metabolized to produce significant amounts of SA in the body for the prior 60 days through the end of the study.
• Any changes in diet or exercise routine in the prior 30 days. Subjects are strongly discouraged from making any changes to their diet and exercise routines following enrollment.
• Receiving concomitant oral medications that are substrates for CYP2B6, P-glycoprotein (P-gp) transporters, or breast cancer resistance protein (BCRP) transporters.
• Known hypersensitivity to SA or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.

• Any of the following laboratory abnormalities at Screening:

  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or glutamate dehydrogenase (GLDH) > 3 × upper limit of normal (ULN)
  • Total bilirubin > 2 × ULN
• Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 based on cystatin C.
• Men with a Fridericia-corrected QT interval (QTcF) > 450 msec and women with a QTcF > 460 msec at Screening.
• Presence or history of any condition, laboratory abnormality, or infection that, in the Investigator's judgment, would interfere with participation, pose undue safety risk, or confound interpretation of study results.
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
• Use of any investigational product or investigational medical device within 30 days prior to Screening or requirement for any investigational agent prior to completion of all scheduled study assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1g UX016 -> Extension Period; Participants will be randomized 3:1 to receive UX016 or placebo. Depending on sub-cohort assignment, participants may receive two single doses of UX016 (0.5g and 1g) or one single dose (1g) before starting daily dosing, or they may proceed directly to daily dosing at the assigned 1g dose level. After completing 48 weeks of daily dosing, participants will be eligible to enter the Extension Period, during which all participants will receive UX016.	Drug: UX016; Tablets for oral use
Experimental: 2g UX016 -> Extension Period; Participants will be randomized 3:1 to receive UX016 or placebo. Depending on sub-cohort assignment, participants may receive a single dose of UX016 (2g) before starting daily dosing, or they may proceed directly to daily dosing at the assigned 2g dose level. After 48 weeks of daily dosing, participants will be eligible to enter the Extension Period, during which all participants will receive UX016.	Drug: UX016; Tablets for oral use
Placebo Comparator: Placebo -> Extension Period; Participants will be randomized 3:1 to receive UX016 or placebo. Depending on sub-cohort assignment, participants may receive one or more single doses of placebo before starting daily dosing or they may proceed directly to daily dosing of placebo at the assigned dose level. After 48 weeks of daily dosing of placebo, participants will be eligible to enter the Extension Period, during which all participants will receive UX016.	Drug: UX016; Tablets for oral use; Other: Placebo; Tablets for oral use. Tablets will match the UX016 tablets, but contain no active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Upper Extremity Composite (UEC) Score Change From Baseline	Baseline, 48 Weeks
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to Week 96 (Double Blind and Extension Periods)

Secondary Outcome Measures

Outcome Measure	Time Frame
Lower Extremity Composite (LEC) Score Change From Baseline	Baseline, 48 Weeks
6-Minute Walk Test (6MWT) Change From Baseline	Baseline, 48 Weeks
GNEM Functional Activities Scale (GNEM-FAS) Change From Baseline	Baseline, 48 Weeks
Plasma Area Under the Curve (AUC) of UX016 and Free Sialic Acid (SA)	Baseline, 12 Weeks
Plasma Maximum Concentration (Cmax) of UX016 and SA	Baseline, 12 Weeks
Excretion in Urine of UX016 and SA	Baseline, 12 Weeks
Free, Total, and Calculated Bound Sialic Acid (SA) in Muscle (Quadriceps) Change From Baseline	Baseline, 12 Weeks

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Ultragenyx Transparency Commitment

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Hereditary Inclusion Body Myopathy (HIBM); Distal Myopathy with Rimmed Vacuoles (DMRV); Nonaka Myopathy; GNEM; Inclusion Body Myopathy 2 (IBM2)
• Additional Relevant MeSH Terms: Distal myopathy, Nonaka type
• Other Study ID Numbers: UX016-CL210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No