Clinical Trials

Date: 2017-06-14

Type of information: Presentation of results at a congress

phase: 2b

Announcement: presentation of results at the annual European Congress of Rheumatology (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. Vobarilizumab (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. As part of the agreement, Ablynx is responsible for Phase II clinical development of ALX-0061 in both RA and systemic lupus erythematosus (SLE). If phase 2b 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.

Disease: moderate to severe rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Georgia, USA

Trial details:

• The purpose of this study is to assess the efficacy and safety of dose regimens of ALX-0061 administered subcutaneously (s.c.) in combination with methotrexate (MTX) to subjects with active RA despite MTX therapy, compared with placebo. The study will also assess the effects of ALX-0061 on quality of life, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061. Finally the trial aims to define the optimal dose regimen for ALX-0061, based on safety and efficacy, for further clinical development.
• The study enrolled 345 subjects in Europe, Latin America and the United States, who were randomly assigned to placebo plus MTX or one of the four dose groups of vobarilizumab administered subcutaneously plus MTX. Subjects were evaluated for efficacy up to and including week 24 and for safety up to and including week 34. Following completion of the 24-week study, eligible subjects were then invited to enroll in an open-label extension study, with 94% accepting. The primary endpoint is the ACR20 response at week 12. In accordance with the study protocol, any subject who did not achieve a 20% improvement from baseline in both swollen and tender joint count at any of the visits at week 12, 16 or 20 had to discontinue from the trial – this was an unusual requirement brought about by the desire to carry out a 24-week study with sc vobarilizumab for which there was only limited supporting data available. The secondary endpoints include higher levels of response assessments, documentation of efficacy over time, as well as the effects on the improvement in physical function and health-related quality of life. Other planned assessments include the determination of serum levels of vobarilizumab, biomarkers, safety, tolerability and immunogenicity. (NCT02309359)

Latest news:

• • On June 14, 2017, Ablynx announced that it 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). The impact of treatment with vobarilizumab on remission and maintenance of efficacy in patients with moderate-to-severe RA despite treatment with methotrexate has been presented during an oral session (OP0098).
• • On August 9, 2016,  Ablynx announced compelling topline results from a second Phase IIb RA study with vobarilizumab, which showed that treatment with vobarilizumab strongly decreased signs and symptoms of rheumatoid arthritis in patients with moderate to severe disease already being treated with methotrexate (MTX). The double-blind study enrolled 345 subjects in Europe, Latin America and the United States, who were randomly assigned to one of the four dose groups of subcutaneously (sc) administered vobarilizumab plus methotrexate [75 mg every 4 weeks (Q4W), 150 mg Q4W, 150 mg Q2W, 225 mg Q2W] or placebo plus methotrexate.
• At week 12, a 20% improvement in American College of Rheumatology scores (ACR20), the primary endpoint of the study, was seen in up to 81% of vobarilizumab-treated patients. From week 12 to week 24, vobarilizumab induced continued improvement in higher level responses with ACR50 and ACR70 scores of up to 59% and 43% respectively at week 24. Moreover, the results demonstrate that vobarilizumab has a rapid and strong impact on disease activity with up to 49% of vobarilizumab-treated patients achieving clinical remission at week 24 compared to 17% of patients receiving placebo.
• The interim safety results through week 24 confirm vobarilizumab’s excellent safety profile which offers the potential for a clear competitive advantage over other anti-IL-6/IL-6R drugs. Treatment-emergent adverse events that led to study drug discontinuation were reported in 6.5% of all vobarilizumab treated patients compared to 4.3% for placebo. Treatment-related serious adverse events were reported in only 1.8% of all vobarilizumab treated patients compared to 2.9% for placebo and there was no observed dose dependency. Clinically meaningful abnormalities in liver function and neutrophil counts were infrequent across the study. Moreover, no grade 3 decreases in absolute platelet counts4 were observed and vobarilizumab had no effect on the mean LDL/HDL cholesterol ratio across all doses tested.
• • On March 17, 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 in combination with methotrexate (MTX) in adult patients with active RA, despite MTX therapy. The study aims to identify the optimum dose and frequency of administration of ALX-0061 for the next phases of development. The current Phase IIb study is a multi-centre, randomised, double-blind, placebo-controlled dose-range finding study of ALX-0061, administered subcutaneously in combination with MTX agent for patients with RA), in subjects with moderate to severe RA, despite MTX therapy. The study is expected to enrol 330 subjects in the United States, Europe and South America, who will be randomly assigned to placebo or four different dose groups of ALX-0061 administered subcutaneously. Administration will be performed every 2 weeks or every 4 weeks. Subjects will be followed for efficacy up to and including week 24 and for safety up to and including week 34. Following completion of the 24-week study, eligible subjects will be invited to participate in an open-label extension study.
• The primary endpoint is the ACR20 response at week 12, a broadly accepted clinical response measure to demonstrate reduction in RA signs and symptoms. The secondary endpoints include higher level of response assessments, documentation of efficacy of ALX-0061 over time, as well as of the effects of ALX-0061 on the improvement in physical function and health-related quality of life. Other planned assessments include the determination of ALX-0061 levels, biomarkers, safety, tolerability and immunogenicity. Ablynx expects top line results from the study before the end of 2016.

Is general: Yes