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 main goal of this study is to evaluate the safety of UX016 and to evaluate the impact of UX016 on muscle strength in adults with GNE Myopathy (GNEM).

Study Overview

• Status: Not yet 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
      • Clinical Trial Site
  • New Jersey
    • Iselin, New Jersey, United States, 08830
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• A confirmed diagnosis of GNEM (also known as hereditary inclusion body myopathy [HIBM], distal myopathy with rimmed vacuoles [DMRV], 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.

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 (GFR) < 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: Lower Dose UX016 -> Extension Period; Participants will be randomized 3:1. Those randomized to lower dose will receive UX016 daily following up to two single dose administrations. After 48 weeks of daily dosing, participants will be eligible to enter the extension period.	Drug: UX016; Tablets for oral use
Experimental: Higher Dose UX016 -> Extension Period; Participants will be randomized 3:1. Those randomized to higher dose will receive UX016 daily following a single dose administration. After 48 weeks of daily dosing, participants will be eligible to enter the extension period.	Drug: UX016; Tablets for oral use
Placebo Comparator: Placebo -> Extension Period; Participants will be randomized 3:1. Those randomized to placebo will receive placebo per the same Lower or Higher Dose UX016 cohorts. After 48 weeks of daily dosing, participants will be eligible to enter the extension period and receive UX016 at the cohort assigned dose level.	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
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to Week 104
Upper Extremity Composite (UEC) Score Change From Baseline	Baseline, 48 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Free and Total Sialic Acid (SA) in Muscle (Quadriceps) Change From Baseline	Baseline, 12 Weeks
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

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): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 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