An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis
- Registration Number
- NCT06664814
- Lead Sponsor
- National Human Genome Research Institute (NHGRI)
- Brief Summary
Background:
Focal segmental glomerulosclerosis (FSGS) is a disease that causes scarring in parts of the kidneys that filter waste. This can lead to protein loss in the urine, which can worsen kidney function. The kidneys may fail over time, and dialysis or a kidney transplant may be needed. Other treatments for this disease do not always work and often have adverse effects. Better treatments for FSGS are needed.
Objective:
To test a study drug (ManNAc) in people with FSGS.
Eligibility:
People aged 18 years and older with FSGS.
Design:
Participants will have 6 to 7 clinic visits over 14 weeks. Two of the visits will require overnight stays for 2 or 3 nights.
ManNAc is a white powder that comes in a sachet. It is dissolved in water and taken twice a day by mouth. Participants will take their first dose at the clinic. They will learn how to store ManNAc and prepare each dose. They will record their doses in a diary. They will also write down any adverse effects or troubles they have using the drug at home.
During clinic visits, participants will have physical exams with blood and urine tests. They will complete questionnaires about their health, sleep habits, and fatigue symptoms.
During overnight visits, participants will also have 24-hour urine collection.
A study team member will call participants 1 week after the first dose to check on their health. Follow-up phone calls will then be every 2 weeks after each clinic visit.
Participants may meet with a dietitian to discuss nutrition while taking the ManNAc.
Participants may choose to have genetic tests.
- Detailed Description
Study Description:
Phase 2, open-label, single-arm, single-center study of ManNAc 2,000 mg oral (PO) twice daily (BID) for 12 weeks in 15 subjects with primary focal segmental glomerulosclerosis (FSGS). The study will characterize the long-term safety, tolerability, pharmacokinetics, and efficacy of ManNAc for proteinuria reduction in subjects with primary FSGS. We hypothesize that ManNAc will be safe and well-tolerated and will reduce proteinuria in subjects with primary FSGS.
Objectives:
Primary Efficacy Objective:
Determine the efficacy of ManNAc therapy in reducing proteinuria in subjects with primary FSGS.
Primary Safety Objective:
Assess the long-term safety and tolerability of orally administered ManNAc to subjects with primary FSGS.
Secondary Objectives:
* Evaluate the long-term pharmacokinetic characteristics of ManNAc 2,000 mg PO BID administered to subjects with eGFR \>=45ml/min/1.73msq.
* Evaluate the percent of subjects achieving partial or complete remission.
Exploratory Objectives:
* Evaluate the impact of ManNAc on symptom burden and functional status using patient-reported outcomes measures (PROMs).
* Evaluate the effect of ManNAc on clinical measures of renal function other than proteinuria.
* Evaluate the change in proteinuria as assessed by 24-hr urine collection.
* Assess variations in the clinical response to ManNAc therapy depending on whether glomerular hyposialylation is present or absent in pre-study renal biopsy samples.
* Assess variations in the clinical response to ManNAc therapy based on the presence of genetic variants in APOL1 in study subjects.
Endpoints:
Primary Endpoint:
Percentage reduction in proteinuria as assessed with urine protein/creatinine ratio (UPCR) from baseline through 12 weeks of ManNAc therapy.
Primary Safety Endpoint:
Demonstrate safety and tolerability by assessing the frequency of adverse events (AEs) in subjects as obtained from in-person assessments, clinical laboratory tests, vital signs, electronic diaries, and physical examinations.
Secondary Endpoints:
* To characterize plasma pharmacokinetics of ManNAc 2,000mg PO BID in subjects with eGFR \>=45ml/min/1.73m\^2.
* Proportion of FSGS patients meeting the FSGS Partial Remission of Proteinuria Endpoint (FPRE), defined as \>40% UPCR reduction from baseline value and with an absolute value \<1.5 g/g at the end of 12 weeks of therapy.
* Proportion of FSGS patients achieving complete remission (CR) defined as absolute value of UPCR \<0.3 g/g at the end of 12 weeks of treatment.
Exploratory Endpoints:
* Change in PROMs as measured using the generic questionnaire Patient Reported Measurement Information System (PROMIS), from baseline to 12 weeks of ManNAc therapy.
* Change in eGFR slope of a linear regression line from baseline through 12 weeks.
* Proportion of FSGS patients with at least a 27% (geometric mean) reduction in urine albumin/creatinine ratio (UACR) from baseline values at end of 12 weeks of therapy.
* Reduction in 24-hr urine protein excretion from baseline after completion of ManNAc therapy at 12 weeks.
* Assess differences in endpoints based on the extent of glomerular hyposialylation in pre-study renal biopsy samples.
* Assess differences in endpoints based on presence of APOL1 genetic variants.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description open label, single arm ManNAc -
- Primary Outcome Measures
Name Time Method Assess the long-term safety and tolerability of orally administered ManNAc to subjects with primary FSGS. 12-weeks. Determine the efficacy of ManNAc therapy in reducing proteinuria in subjects with primary FSGS. 12-weeks.
- Secondary Outcome Measures
Name Time Method Evaluate the long-term pharmacokinetic characteristics of ManNAc. 8-months. Evaluate the percent of subjects achieving partial or complete remission. 8-months.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States