ACE Reno, Pico Cell Matrix and Its Effect on eGFR in Chronic Kidney Diseases

Study Objectives

Primary Objective:

To evaluate the effect of ACE Reno on urinary albumin-to-creatinine ratio (ACR) after 12 weeks of treatment in patients with nephropathy of diverse etiologies.

Secondary Objectives:

To assess the effect of ACE Reno on estimated glomerular filtration rate (eGFR) slope.

To evaluate changes in proteinuria, blood pressure, and patient-reported outcomes.

To assess safety and tolerability.

Exploratory Objectives:

To explore biomarker changes (e.g., TGF-β, cGMP, NGAL, KIM-1). To assess durability of response up to 6 months in responders. Investigational Product (IP) ACE Reno is a sublingual solution (1 mL four times daily for 12 weeks) containing a standardized panel of low-molecular-weight bioactive peptides and amino acids.

Key peptide domains include:

BMP-7-like sequences countering TGF-β-driven fibrosis. HGF-like fragments supporting epithelial repair. Klotho-like motifs antagonizing profibrotic pathways and RAAS/Wnt activity. Natriuretic-peptide-like domains enhancing cGMP signaling, with anti-fibrotic, vasodilatory, and endothelial-protective effects.

No genetic material is present; formulation is peptide-based only. Study Design Type: Prospective, multicenter, interventional, open-label. Model: Single-arm with within-patient comparisons. Duration: 12 weeks treatment + 4 weeks post-treatment safety follow-up. Visits: Screening, Baseline (Day 0), Week 4, Week 8, Week 12, and Week 16 safety call.

Participants

Inclusion:

Adults (≥18 years) with nephropathy of any degree (microalbuminuria, overt proteinuria, CKD stages 1-5 not on dialysis, or post-transplant with proteinuria). Stable background therapy with ACEi/ARB, SGLT2i, or MRA allowed.

Exclusion:

Dialysis at baseline. Recent kidney transplant (\<12 months). Uncontrolled acute infection or unstable autoimmune disease. Pregnancy or lactation. Known hypersensitivity to study components. Categories (Strata: 17 Subgroups) Diabetic nephropathy - microalbuminuria Diabetic nephropathy - macroalbuminuria Diabetic nephropathy - CKD Stage 3 Diabetic nephropathy - CKD Stage 4-5 (non-dialysis) Hypertensive nephropathy - microalbuminuria Hypertensive nephropathy - proteinuric CKD Hypertensive nephropathy - advanced CKD (3-5) Autoimmune nephropathy - Class II-III Autoimmune nephropathy - Class IV-V Reflux nephropathy - mild/moderate scarring Reflux nephropathy - severe scarring Chronic glomerulonephritis - nephrotic range proteinuria Chronic glomerulonephritis - CKD \<60 mL/min/1.73m² CKD of unknown etiology - Stage 1-2 CKD of unknown etiology - Stage 3-4 ESRD pre-dialysis (eGFR \<15) Post-transplant CKD with proteinuria Sample Size and Rationale

Primary endpoint powering (paired design):

Detect 30% reduction in ACR (δ = ln(0.70) = -0.357), assuming σ = 0.8, r = 0.6 → \~32 analyzable patients needed.

Planned enrollment (pooled cohort, with 17 categories):

\~182 analyzable patients (\~214 enrolled allowing for 15% attrition). Each category will include a minimum of 8-12 patients (more for common etiologies such as diabetic proteinuria).

Total enrollment stratified by prevalence across categories. Endpoints

Primary Endpoint:

Change in urinary ACR from baseline to Week 12 (log-transformed).

Secondary Endpoints:

Change in eGFR slope. Change in 24-h proteinuria (selected patients). Blood pressure change. Patient-reported outcomes (KDQOL-36, EQ-5D). Safety (hyperkalemia, creatinine rise, liver tests, hematology).

Exploratory Endpoints:

Biomarker profiles (TGF-β, cGMP, NGAL, KIM-1). Hospitalization rate. Extended follow-up outcomes at 6 months. Follow-Up Plan

Monthly Visits (Week 4, 8, 12):

Clinical: BP, vitals, weight, adherence. Labs: creatinine/eGFR, electrolytes, liver panel, CBC, urine ACR. Safety: hyperkalemia, creatinine rise. PROs brief (fatigue, QoL).

Final (Week 12):

Primary endpoint assessment (duplicate ACR). PROs full set. Investigator global assessment.

Safety Call (Week 16):

AE/SAE resolution, concomitant therapy updates. Statistical Analysis Primary analysis: Paired t-test and mixed model for repeated measures (MMRM) on log(ACR).

Secondary: eGFR slope via linear mixed model, BP change via ANCOVA, responder rate (≥30% reduction in ACR).

Subgroups: Category-by-time interaction analysis; forest plots for effect estimates.

Multiplicity: Subgroup effects exploratory; overall primary endpoint tested at α=0.05.

• Change in Estimated Glomerular Filtration Rate (eGFR) slope [Time frame: Baseline, Week 4, Week 8, Week 12]
• Change in 24-hour Proteinuria [Time frame: Baseline to Week 12 (subset of participants with baseline nephrotic-range proteinuria)]
• Change in Blood Pressure [Time frame: Baseline, Week 4, Week 8, Week 12]
• Safety and Tolerability [Time frame: Throughout treatment and up to Week 16 follow-up]
• Safety and Tolerability [Time frame: Throughout treatment and up to Week 16 follow-up]
• Safety and Tolerability [Time frame: Throughout treatment and up to Week 16 follow-up]
• Safety and Tolerability [Time frame: Throughout treatment and up to Week 16 follow-up]
• Safety and Tolerability [Time frame: Throughout treatment and up to Week 16 follow-up]
• Safety and Tolerability [Time frame: Throughout treatment and up to Week 16 follow-up]