First-in-human Study of UX016 in GNEM

Official title

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

Overview

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).

Interventions

• Drug UX016
  Tablets for oral use
• Other Placebo
  Tablets for oral use. Tablets will match the UX016 tablets, but contain no active ingredients

Primary outcome measures

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to Week 104]
• Upper Extremity Composite (UEC) Score Change From Baseline [Time frame: Baseline, 48 Weeks]

Secondary outcome measures (4)

• Free and Total Sialic Acid (SA) in Muscle (Quadriceps) Change From Baseline [Time frame: Baseline, 12 Weeks]
• Lower Extremity Composite (LEC) Score Change From Baseline [Time frame: Baseline, 48 Weeks]
• 6-Minute Walk Test (6MWT) Change From Baseline [Time frame: Baseline, 48 Weeks]
• GNEM Functional Activities Scale (GNEM-FAS) Change From Baseline [Time frame: Baseline, 48 Weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• Clinical Trial Site — Orange
• Clinical Trial Site — Iselin

Identifiers

NCT: NCT07511556 · UX016-CL210

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗