NCT02639260

A Phase 1 Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ManNAc in Subjects With Primary Podocyte Diseases

Completed Phase 1 Last updated 24 February 2023

What this trial tests

Phase 1 trial testing N-acetyl D-mannosamine in Kidney Disease in 10 participants. Completed in 5 June 2018.

Timeline

7 July 2016

Primary endpoint
5 June 2018

5 June 2018

Quick facts

Lead sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	7 July 2016
Primary completion	5 June 2018
Estimated completion	5 June 2018
Sites	1 location across United States

Drugs / interventions tested

• N-acetyl D-mannosamine — full drug profile →

Conditions studied

• Kidney Disease — all drugs for Kidney Disease →

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Who can join

18 and older, any sex, with Kidney Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Three kidney diseases that affect both children and adults are minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN). These diseases are characterized by proteinuria (protein in the urine) and in the cases of FSGS and membranous nephropathy, a tendency to progressive scarring of the glomerulus (the filtering units of the kidneys) that leads to end-stage kidney disease. Several therapies are available for these diseases, but these therapies do not provide lasting reduction in proteinuria for many subjects. In the current study, carried out at the NIH Clinical Center, we are testing a new therapy, ManNAc. ManNAc is a naturally occurring uncharged sugar that cells use to produce negatively charged sialic acid. Kidney cells attach sugars such as sialic acids to proteins and lipids (resulting in glycans), and these assist in cell function. Mouse models of the inherited muscle disease GNE myopathy, which is due to sialic acid deficiency on muscle glycans, responded favorably to oral ManNAc therapy and a clinical trial of ManNAc is ongoing in GNE myopathy subjects. There is evidence that some subjects with MCD, FSGS or MN do not put enough sialic acids on glomerular proteins and so ManNAc therapy may increase sialic acid production and sialylation of glomerular proteins in these subjects. For the present study, we will recruit 12 subjects who have MCD, FSGS or MN. Each subject will stay at the NIH Clinical Center for 11 days to receive oral ManNAc. The primary purposes of the study are to determine: 1) the safety of ManNAc in subject s with kidney disease; and 2) the ManNAc and sialic acid metabolism related to ManNAc in subjects with kidney disease. Concentrations of ManNAc and sialic acid will be measured in plasma at various times before and after dosing. If this study suggests that ManNAc is safe in subject with kidney disease, the results will be used to plan a longer-term study to determine whether it is effective at reducing proteinuria....

Publications & conference data

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

1. Podocytopathies.
   Kopp JB, Anders HJ, Susztak K, Podestà MA, et al · · 2020 · cited 427× · PMID 32792490 · DOI 10.1038/s41572-020-0196-7
2. Rationale and Design for a Phase 1 Study of <i>N</i>-Acetylmannosamine for Primary Glomerular Diseases.
   Huizing M, Yardeni T, Fuentes F, Malicdan MCV, et al · · 2019 · cited 14× · PMID 31701055 · DOI 10.1016/j.ekir.2019.06.012
3. Elevated plasma free sialic acid levels in individuals with reduced glomerular filtration rates.
   Fuentes F, Carrillo N, Wilkins KJ, Blake J, et al · · 2020 · cited 4× · PMID 33969317 · DOI 10.34067/kid.0002122020
4. Perhaps a wee bit of sugar would help.
   Freeze HH. · · 2016 · cited 3× · PMID 27350601 · DOI 10.1038/ng.3600
5. Phase 1 Study of Oral N-Acetylmannosamine in Primary Podocytopathies.
   Huizing M, Ganguli A, Bolaños J, Leoyklang P, et al · · 2026 · PMID 41630898 · DOI 10.1016/j.ekir.2025.103758