close

Clinical Trials

Date: 2017-06-14

Type of information: Presentation of results at a congress

phase: 2b

Announcement: presentation of results at the European League Against Rheumatism Annual Congress (EULAR)

Company: Ablynx (Belgium)

Product: vobarilizumab (ALX-0061)

Action mechanism: antibody/nanobody. IL-6 and its receptor IL-6R are involved in the pathogenesis of various inflammatory and auto-immune diseases, including RA. ALX-0061 is a Nanobody binding to the interleukin-6 receptor (IL-6R). It has been developed for the treatment of RA and possibly systemic lupus erythematosus (SLE). IL-6 is a pro-inflammatory cytokine that plays a role in T-cell activation, production of acute phase proteins in response to inflammation, induction of immunoglobulin production, and stimulation of osteoclast differentiation and activation. ALX-0061 (26kD) has a very strong affinity for the soluble IL-6R and contains an anti-IL-6R Nanobody linked to an anti-human serum albumin (HSA) Nanobody, thereby increasing the in vivo serum half-life. Phase I/II proof-of-concept results with ALX-0061 were published in February 2013, followed by the signing of a global exclusive licensing deal with AbbVie in September 2013 for the development and commercialisation of ALX-0061.

Disease: moderate to severe rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Hungary, USA

Trial details:

  • This Phase IIb study is a multi-centre, randomised study consisting of two parallel treatment groups: a double-blind part to assess the efficacy and safety of ALX-0061 sc and an open-label part (with a blinded independent joint-assessor) with tocilizumab sc, which is not used as an active comparator but to provide parallel efficacy and safety data for sc tocilizumab in the same RA patient population.  The secondary objectives of this study are:
  • To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX 0061 and to explore potential dose regimens for ALX 0061 monotherapy, based on safety and efficacy, for further clinical development.
  • To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.
  • The study is expected to enrol 228 subjects in the United States, Europe and South America, who will be randomly assigned to three different dose groups of ALX-0061 sc or one dose group of tocilizumab sc. Administration of ALX-0061 will be performed every 2 weeks or every 4 weeks for 12 weeks. Subjects will be followed for efficacy up to week 12 and for safety until 12 weeks after last dosing. Following completion of the 12-week dosing, eligible subjects will be invited to participate in an open-label extension study. (NCT02287922)

Latest news:

  • • On June 14, 2017, Ablynx has presented additional data from a Phase IIb study in rheumatoid arthritis (RA) with its anti-IL-6R Nanobody®, vobarilizumab, at the annual European Congress of Rheumatology (EULAR), being held from 14-17 June 2017 in Madrid (Spain).
  • • On July 7, 2016, Ablynx announced that its anti-IL-6R Nanobody®, vobarilizumab (ALX-0061), successfully completed a 12 week treatment and assessment period in a Phase IIb monotherapy study in patients with moderately to severely active rheumatoid arthritis (RA) who are intolerant to methotrexate or for whom continued methotrexate treatment is inappropriate. The objective of the study was to explore the efficacy and safety of various dose regimens for vobarilizumab monotherapy to guide further clinical development, and to obtain parallel descriptive information for tocilizumab in the same clinical trial RA population. The study enrolled 251 subjects in the United States, Europe and South America, who were randomly assigned to one of the three blinded dose groups of subcutaneously (sc) administered vobarilizumab [150 mg every 4 weeks (Q4W), 150 mg every 2 weeks (Q2W), 225 mg every 2 weeks (Q2W)] or open-label sc tocilizumab, with the vast majority (94%) receiving weekly tocilizumab dosing. Subjects were evaluated for efficacy and safety up to week 12 and eligible subjects on vobarilizumab were then invited to enroll in an open-label extension study, with 91% accepting. Subjects who were not eligible to roll over or who did not elect to do so were followed for safety for an additional 12 weeks after the last dosing. Evaluation is ongoing for a minority of these subjects.
  • The topline ACR efficacy results demonstrate that vobarilizumab appears to be very effective with less frequent administration than tocilizumab. In addition, based on the change from baseline in the health assessment questionnaire disability score (HAQ-DI), vobarilizumab seems to have a rapid positive impact on patients’ physical function. Importantly, vobarilizumab induces either clinical remission or low disease activity (based on DAS28CRP) in up to 60% of patients at week 12.
  • Subjects received tocilizumab [(Ro)Actemra®, an anti-IL-6R monoclonal antibody marketed by Roche/Chugai] according to the following dosing regimen: 1) US: 162 mg every 2 weeks (subjects weighing < 100kg) or every week (for subjects weighing ? 100 kg). 2) EU/South-America: 162 mg every week for all subjects ACR criteria measure improvement in tender and swollen joint counts and improvement in three of five other disease-activity measures; ACR20 measures % of patients with 20% improvement; ACR50 measures % of patients with 50% improvement and ACR70 measures % of patients with 70% improvement
  • The interim safety results through week 12 confirmed the favourable safety profile of vobarilizumab at all doses tested and its side effect profile did not change with increased dose. Treatment-emergent adverse events were similar across the different groups and only 2.1% of vobarilizumab treated patients discontinued study drug due to adverse events compared with 6.3% for the tocilizumab group. Serious treatment-related adverse events occurred in 0.5% of vobarilizumab treated patients as compared to 3.1% for the tocilizumab group. Liver function abnormalities were not frequent across the study and no grade 3 decreases in absolute platelet counts were observed. While infrequent, study drug discontinuations due to a decrease in absolute neutrophil count were less commonly observed with vobarilizumab than with tocilizumab. At week 12, there were no meaningful changes from baseline in the mean LDL/HDL cholesterol ratio across all groups.
  • • On April 7, 2015, Ablynx announced that it has administered the first dose in the Phase IIb study to evaluate the efficacy and safety of its anti-IL-6R Nanobody®, ALX-0061, administered subcutaneously (sc) as a monotherapy in adult patients with active RA who are intolerant to methotrexate (MTX), or for whom MTX is inappropriate. The study also aims to obtain parallel descriptive information concerning the efficacy and safety of administration of sc tocilizumab (Actemra®, RoActemra®) in the same RA population. The first Phase IIb study with ALX-0061 in combination with MTX in patients with active RA started on 17 March 2015.
  • Ablynx expects top line results from the two Phase IIb studies in RA before the end of 2016. If the results meet pre-defined success criteria, AbbVie will exercise its right to in-license ALX-0061 and be responsible for subsequent Phase III clinical development and commercialisation.

Is general: Yes