Table 1.
Studies of the pharmacokinetics and clinical efficacy of tildrakizumab.
| Study (year) | Study type | Participants | Objectives | Results |
|---|---|---|---|---|
| Zandvliet and colleagues9 | Open-label phase I | Part 1: 53 male and female Japanese, White and Chinese participants without psoriasis ages 18–55 years |
• Assess pharmacokinetics and tolerability of tildrakizumab 50–400 mg SC • Evaluate differences in pharmacokinetics of tildrakizumab among ethnicities |
• Drug exposure over time increased proportionally with increased SC dosing. • Absolute bioavailability for tildrakizumab SC in Japanese patients was 92%. • Dosing with 50–400 mg SC was well-tolerated. • Maximum drug concentration, drug exposure over time, mean drug half-life, and median time to maximum was similar in Japanese, Chinese and White patients treated with tildrakizumab SC. |
| Part 2: 6 male and female Japanese patients without psoriasis ages 18–55 years |
• Assess tolerability of tildrakizumab 10 mg/kg IV | • Dosing with 10 mg/kg IV was well-tolerated. | ||
| Khalilieh and colleagues10 | Randomized, placebo-controlled phase I | Study 1 (P05661): 29 participants without psoriasis ages 18–45 years at a single site in Melbourne, Australia |
• Assess pharmacokinetics and tolerability of ascending tildrakizumab IV doses (0.1–10 mg/kg) | • Drug exposure over time and maximum drug concentration increased proportionally with increased SC and IV dosing concentrations. • Systemic clearance of drug following IV and SC dosing was slow, and half-life was long (ranging from 26.8 to 32.4 days). • Half-life significantly decreased (to 10.1 and 13.5 days) in 2 of 6 patients who tested positive for ADAs to tildrakizumab. • Bioavailability for 50 mg SC and 200 mg SC were 80% and 73%, respectively. • All SC and IV doses tested were well-tolerated. |
| Study 2 (P05776): 37 participants without psoriasis ages 18–45 years at a single site in Melbourne, Australia |
• Assess pharmacokinetics and tolerability of ascending tildrakizumab SC doses (50–200 mg) • Determine the relative bioavailability of ascending tildrakizumab SC doses |
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| Kopp and colleagues12 | Randomized, placebo-controlled phase I proof-of-concept | 77 male and female patients with moderate-to-severe plaque psoriasis ages 18–65 years at nine sites | • Assess pharmacokinetics of tildrakizumab 0.05–10 mg/kg IV • Evaluate clinical efficacy of tildrakizumab 0.05–10 mg/kg IV versus placebo through PASI reduction outcomes |
• Half-life of IV dosing was long, ranging from 20.6 to 26.9 days. • Dosing with 3 mg/kg and 10 mg/kg led to achievement of PASI-75 in the majority of patients between 16 and 28 weeks following initiation of treatment. • Following drug discontinuation at 28 weeks, clinically meaningful PASI score reduction persisted through 36 weeks. |
| Papp and colleagues11 | Randomized, placebo-controlled, parallel group phase IIb | 355 male and female patients with moderate-to-severe plaque psoriasis ages 18–82 years at 64 sites in USA, Canada, Japan, and Europe | • Evaluate clinical efficacy of tildrakizumab 5–200 mg SC versus placebo through PASI reduction and PGA improvement outcomes | • Increasing SC dosing correlated with improvements in PASI scores and PGA scores versus placebo. • The majority of patients treated with 100 mg or 200 mg for 52 weeks (dosing at week 0, week 4, and then every 12 weeks) showed maintained PASI-75 response at 16 weeks following drug discontinuation. • Increased serum tildrakizumab levels correlated with a greater likelihood of achieving PASI-75. In patients receiving 200 mg dosing, serum levels were similar in clinically responsive and nonresponsive patients. |
| Reich and colleagues16 | Randomized, placebo-controlled, parallel group phase III | Study 1 (reSURFACE1): 772 male and female patients with moderate-to-severe plaque psoriasis ages 18 years and older at 118 sites in Australia, Canada, Japan, the UK, and USA |
• Evaluate clinical efficacy of tildrakizumab 100 mg and 200 mg SC versus placebo through PASI reduction, PGA improvement, and DLQI improvement outcomes | • Compared with patients treated with placebo, those treated with 100 mg and 200 mg tildrakizumab SC had significantly greater achievement of PASI-75 and dramatic decreases in PGA and DLQI scores after 12 weeks of treatment. • Dosing with 100 mg and 200 mg tildrakizumab SC has similar clinical efficacy with respect to percent of patients who attain PASI-75 by 28 weeks. • Compared with patients treated with etanercept 50 mg, those treated with 200 mg tildrakizumab SC had significantly higher rate of attainment of PASI-75 by week 12, PGA responses of 0 or 1 by week 12, and DLQI responses of 0 or 1 by week 28. This was not observed in patients treated with tildrakizumab 100 mg SC. |
| Study 2 (reSURFACE2): 777 male and female patients with moderate-to-severe plaque psoriasis ages 18 years and older at 132 sites in Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Italy, Israel, Netherlands, Poland, and USA |
• Evaluate clinical efficacy of tildrakizumab 100 mg and 200 mg SC versus placebo and etanercept 50 mg through PASI reduction, PGA improvement, and DLQI improvement outcomes |
ADA, antidrug antibody; DLQI, Dermatology Quality of Life Index; IV, intravenous; PASI, Psoriasis Area and Severity Index; PGA, Physician’s Global Assessment; SC, subcutaneous.