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Table 3 Overview of results obtained in the CIA study in rhesus monkeys

From: The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis

Compound Animal ID Day of CRP >50 mg/mLa CRP maximumb (mg/ml) Day with Clinical score = 5c Day of sacrificed Early responder Neutralizing or clearing ADAs (based on PK and sIL-6R) Body weight at day of sacrifice or day 70 Swelling score at day of sacrifice or day 70
Placebo 95020 24 547.5 NA 39 No NA -23 % 8
Placebo R05029 21 191.5 NA 44 No NA -20 % 12.5
Placebo R05053 24 535.6 NA 52 No NA -25 % 37
Placebo R05058 17 547.2 NA 38 No NA -25 % 14
Placebo R05073 14 643.1 28 29 Yes (CRP) NA   
7.5 mg/kg ALX-0061 R00060 17 151.6 21 22 Yes (Cl Sc) No   
7.5 mg/kg ALX-0061 R01016 35 101.9 35 34 No Yes (Day 34)   
7.5 mg/kg ALX-0061 R02055 NA <50 NA 70 No No -10 % 0
7.5 mg/kg ALX-0061 R03014 17 128.1 NA 49 No Yes (Day 28)   
7.5 mg/kg ALX-0061 R05012 21 188.9 NA 44 No Yes (Day 34)   
7.5 mg/kg ALX-0061 R05042 NA <50 NA 70 No No -15 % 2
7.5 mg/kg ALX-0061 R06003 17 50.6 17 17 Yes (Cl Sc) No   
10 mg/kg tocilizumab 95031 NA <50 NA 70 No No +4 % 0
10 mg/kg tocilizumab BB226 24 367.3 28 28 No Yes (Day 28)   
10 mg/kg tocilizumab R04042 28 448.1 31 31 No Yes (Day 28)   
10 mg/kg tocilizumab R05059 NA <50 NA 70 No No +6 % 0
10 mg/kg tocilizumab R05061 21 453.0 31 31 No Yes (Day 24)   
10 mg/kg tocilizumab R05089 28 161.7 NA 70 No Yes (Day 28)   
10 mg/kg tocilizumab R05090 21 171.1 21 21 Yes (Cl Sc) Yes (Day 21)   
  1. Treatment was started seven days after sensitization with chicken collagen type II. Animals were administered weekly for six consecutive weeks by intravenous bolus injection. ALX-0061 was given at 7.5 mg/kg, and TCZ at 10 mg/kg. Data were processed as follows: body weight was normalized to pre-dose weight (day 0); Body weight and swelling score are not included for early responders and animals which showed a clearing and/or neutralizing ADA response. Early responders were identified via CRP or clinical score. Animals which had active exposure throughout the study (that is, no neutralizing and/or clearing ADA) are highlighted in bold
  2. aStudy day that a CRP level of more than 50 mg/ml was measured for the first time, starting after day 10 (subsiding of the acute CFA response); increasing CRP levels after day 10 are interpretable as a sign of disease severity
  3. bMaximum CRP values measurable for the given animal after day 10; these concentrations are interpretable as a measure of disease severity
  4. cStudy day on which a maximum clinical score of five was reported; this is interpretable as a measure of disease severity, with early onset being a hard-to-treat disease course
  5. dAnimals with high discomfort scores had to be euthanized during the study period
  6. ADA: anti-drug antibodies; CFA: complete freund’s adjuvant; CIA: collagen-induced arthritis; Cl Sc: clinical score; CRP: C-reactive protein; ID: identification; NA: not applicable; PK: pharmacokinetics; sIL-6R: soluble interleukin-6 receptor; TCZ: tocilizumab