November 17, 2006
American Society of Nephrology (ASN) Renal Week 2006, San Diego, CA
Abstract TH-PO239

Dose-escalation phase I study of FG-3019, anti-CTGF monoclonal antibody, in patients with type 1/2 diabetes mellitus and microalbuminuria. Adler SG ¹, Schwartz S ², Williams ME ³, Arauz-Pacheco C ⁴, Bolton WK ⁵, Lee T ⁶, Coker G ⁶, Sewell KL ⁶.

1 LABiomed Res Instit Torrance CA, 2 Diabetes & Glandular Dis. San Antonio TX, 3 Joslin Clinic Boston MA, 4 Radiant Research Dallas TX, 5 U. VA Charlottesville VA, 6 FibroGen So. San Francisco CA.

Abstract: Blood, urine and glomerular CTGF levels correlate with progression of diabetic nephropathy (DN). FG-3019 is a fully human IgG₁ kappa neutralizing CTGF mAb effective in animal DN models.

Subjects were ≥21 yrs with type 1 or 2 DM, BMI ≤32 kg/m², SCr ≤1.1 (women) or ≤1.5 mg/dL (men), with microalbuminuria (MalbU) by first AM urine albumin/Cr ratio (ACR) of 30-300 mg/g. Ten subjects each received 3 or 10 mg/kg on Days 0, 14, 28 and 42, with 1 yr follow-up. The 3 mg/kg cohort is completed. The 10 mg/kg cohort is in progress; only demographic/adverse event (AE) data are included. Enrolled subjects (N=20; 60% male; 20% type I; 50% on insulin; 95% on ACEi and/or ARB) had a mean (±SD) age of 58 (±11), 17 (±7) yrs DM, SCr 0.9 (±0.2) mg/dL, eGFR (MDRD) 84 (±21) mL/min/1.73m², and average MAP 114 (±11) mm Hg. One 3 mg/kg subject withdrew after 1 dose. 8/12 subjects with AE data reported an infusion day AE (flushing, dizzy, headache (HA), anxiety). 5/12 reported a non-infusion day possibly drug-related AE (HA, ↓Na, ↑LFT, paronychia, anemia). There was 1 unrelated SAE (day 343; gastroenteritis) and no severe AEs. For 3 mg/kg cohort: PK on Days 1/42 showed Tmax=2.25/4.12 hrs; Cmax=73/76 ug/mL; clearance=0.42/0.38 mL/hr/kg; T_1/2=3.0/4.3 days. 0/9 pts developed anti-human antibodies. Day 0 ACR and albumin excretion rate (AER) were 48 (±27) mg/g and 80 (±77) mg/d. Day 56 mean ACR=29 (±15), a Δ of -19 (±25) mg/g, and AER was 41 (±22), a Δ of -36 (±68) mg/day. ACR decreased ≥50% in 3/9 pts (57-91 to 23-36 mg/g) and 3/9 pts (1 unique) decreased AER ≥50% (53-205 to 22-83 mg/day). Mean eGFR was stable (Δ= 3.6 ±15 mL/min/1.73m²); mean ΔMAP was -5 (±14) mm Hg.

FG-3019 at 3 or 10 mg/kg was safely dosed over 42 days in DN pts with MalbU. PK showed 1 compartment distribution and saturable clearance. Urine ACR improved ≥50% in 33% of 3mg/kg pts. Anti-CTGF mAb may synergize with ACEi/ARBs.

See also November 17, 2006 press release