Clinical pharmacokinetics of the anti-interleukin-20 monoclonal antibody NNC0109-0012 in healthy volunteers and patients with psoriasis or rheumatoid arthritis.
BACKGROUND
NNC0109-0012, a novel human monoclonal antibody that binds to and neutralizes the activity of interleukin-20, was investigated as a potential treatment for inflammatory diseases. Pharmacokinetic (PK) modeling was performed using data from four completed clinical phase 1/2 trials to better understand the clinical PK of NNC0109-0012.


METHODS
The populations included were patients with rheumatoid arthritis (RA), chronic plaque psoriasis, and healthy volunteers. NNC0109-0012 was administered subcutaneously at various dose levels (0.01-3 mg/kg) as single dose, once weekly, or multiple doses every second week for up to 12 doses. Noncompartmental methods were used to describe the PK parameters. Population PK was analyzed using nonlinear mixed-effects modeling, with body weight as the main covariate and gender, age, and population as additional covariates.


RESULTS
Across studies (N = 116), mean age and body weight ranged from 38 to 58 years and 72 to 96 kg, respectively. NNC0109-0012 displays linear PK. Time to maximum plasma concentration occurred at approximately 1 week, and the terminal half-life was approximately 3 weeks. Clearance and volume of distribution increased proportionally to body weight. No difference in clearance or volume of distribution was observed between gender or different age groups; however, clearance was slightly lower in healthy volunteers than in patients with RA.


CONCLUSIONS
The PK profile of NNC0109-0012 is similar to other monoclonal antibodies directed against soluble targets.
Novo Nordisk A/S, Søborg, Denmark, mslu@novonordisk.com.
Mia Sandberg
MS
Lundblad
Rune Viig
RV
Overgaard
Marie
M
Göthberg
Marianne Scheel
MS
Fjording
Estelle
E
Watson
D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001835:Body Weight; D000080908:Broadly Neutralizing Antibodies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; C000600094:Fletikumab