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OP0043 Twenty-Four Weeks of Treatment with a Novel Anti-IL-6 Receptor Nanobody® (ALX-0061) Resulted in 84% ACR20 Improvement and 58% DAS28 Remission in a Phase I/Ii Study in RA
  1. J.-B. Holz1,
  2. L. Sargentini-Maier2,
  3. S. De Bruyn1,
  4. B. Gachályi3,
  5. I. Udvaros4,
  6. B. Rojkovich5,
  7. S. Bruk6,
  8. P. Sramek7,
  9. M. Korkosz8,
  10. K. Krause9,
  11. P. Schoen10,
  12. J. D’Artois1,
  13. K. Verschueren1,
  14. W. Willems1,
  15. K. De Swert1,
  16. G. Arold11
  1. 1Clinical Development
  2. 2Pharmacology, Ablynx nv, Zwijnaarde, Belgium
  3. 3Fázis I-es Klinikai Farmakológiai Vizsgálóhely, Péterfy Sándor Utcai Kórház
  4. 4PRA International
  5. 5II. sz. Reumatológiai Osztály, Budai Irgalmasrendi Kórház Kht., Budapest, Hungary
  6. 6Interni oddeleni, Nemocnice Trinec, Trinec
  7. 7Pharmaceutical Research Associates CZ, Praha, Czech Republic
  8. 8Profil Reumatologiczny, Malopolskie Centrum Medyczne, Krakow
  9. 9Wojewodzki Szpital, Wroclaw, Poland
  10. 10PM, Ablynx nv, Zwijnaarde, Belgium
  11. 11Medical Affairs, PRA International GmbH, Berlin, Germany

Abstract

Background ALX-0061 is a monovalent IL-6R targeting Nanobody. It inhibits signalling via soluble and membrane IL-6R. PK/PD modelling resulted in a condensed study design, combining single ascending dose (SAD), multiple ascending dose (MAD) and clinical proof-of-concept using PK, biomarker and clinical readouts as decision tools.

Objectives MAD: To determine the efficacy and safety of 24 weeks of dosing in patients with RA and to investigate the tolerance, PK, PD and immunogenicity after multiple dosing with ALX-0061.

Methods Multicentre, randomised, double-blind, placebo controlled, dose escalation, Phase I/II study in patients with active RA on stable MTX therapy. MAD: In the first 12 weeks patients received placebo or ALX-0061 IV infusion at 1 or 3 mg/kg Q4W, or 6 mg/kg Q8W. In the second 12 weeks, patients with insufficient EULAR response were allowed to rollover (placebo) or to intensify dosing to enrich the safety and efficacy population.

Results Thirty-seven patients with active RA from 6 sites in CEE started at 1 mg/kg (10 patients), 3 mg/kg (11 patients), 6 mg/kg (10 patients) or placebo (6 patients). 31 patients continued on ALX-0061 in the 2nd 12 weeks with only 4 changing their dosing regimen and 3 rolling over from placebo. The patients initiated on ALX-0061 had a median duration of disease of 5.7 years, median age of 53 years and median BMI of 26 kg/m2 and moderate-to-severe disease activity (median DAS28 score 4.7; median VAS patient score 49).

ALX-0061 was well tolerated for up to 24 weeks. Clinically relevant neutropenia was absent as well as serious infections. Clinically significant signals in lipids were not observed. No anti-drug antibodies were detected.

After 24 weeks of treatment, a total of 18 patients (58%) on ALX-0061 achieved DAS28 remission, of which 8 achieved Boolean remission. All DAS28 components contributed evenly and onset of remission occurred as early as week 2 for certain patients. Clinically meaningful improvements for bone oedema were observed and the global RAMRIS scores showed no worsening after 24 weeks.

Conclusions The use of modelling enabled a rational study design with 3 biologically effective dose levels. In patients with active RA, rapid and strong effects on the IL-6 pathway were observed and associated with a strong clinical response. Clinically significant improvement of disease activity occurred fast and almost 60% of patients achieved state of remission at the end of 24 weeks. The treatment was well tolerated at all doses and the improvement of signs and symptoms was accompanied by a reduction in bone oedema and absence of radiographic disease progression.

Disclosure of Interest J.-B. Holz Shareholder of: Ablynx, Employee of: Ablynx, L. Sargentini-Maier Shareholder of: Ablynx, Employee of: Ablynx, S. De Bruyn Shareholder of: Ablynx, Employee of: Ablynx, B. Gachályi: None Declared, I. Udvaros: None Declared, B. Rojkovich: None Declared, S. Bruk: None Declared, P. Sramek: None Declared, M. Korkosz: None Declared, K. Krause: None Declared, P. Schoen Shareholder of: Ablynx, Employee of: Ablynx, J. D’Artois Shareholder of: Ablynx, Employee of: Ablynx, K. Verschueren Shareholder of: Ablynx, Employee of: Ablynx, W. Willems Shareholder of: Ablynx, Employee of: Ablynx, K. De Swert Shareholder of: Ablynx, Employee of: Ablynx, G. Arold: None Declared

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