Impact of Clinical Remission on Physical Function in

FRI0329
Impact of Clinical Remission on Physical Function in Patients with Rheumatoid
Arthritis Treated with ALX-0061: Post-hoc Analysis of Phase I/II Data
Katrien Van Beneden1, Katrien Verschueren1, Wouter Willems1, Heidi Wouters1, Joke D’Artois1, Katelijne De Swert1, Gerhard Arold2, Steven De Bruyn1
1Clinical Development, Ablynx nv, Zwijnaarde, Belgium, 2PRA International GmbH, Berlin, Germany
Camelidae family has both forms
CH2
Ablynx’s Nanobody®
•
•
•
•
•
•
•
VH
VL
CH3
CH3
Highly potent, robust and stable
Broad target applicability
Multiple administration routes
Ease of manufacture
Speed of discovery
Heavy-chain antibody
• Only heavy chains
• Full antigen binding
capacity and very stable
Conventional antibody
• Heavy and light chains
• Both chains required for antigen
binding and stability
• Large size and relatively low
formatting flexibility
ALX-0061
(26 kDa)
Anti-HSA
 ALX-0061 product description
• monovalent interaction eliminates IL-6R cross-linking Anti-IL-6R
• no induction of Antibody-dependent cell-mediated cytotoxicity or complementdependent cytotoxicity due to lack of Fc
• half-life extension by binding to Human Serum Albumin (HSA)
Objectives and Methods
• During the first 12 weeks of the multiple ascending dose period, 37 patients
ALX-0061 dose increased or switched from PBO to ALX-0061. 24 patients
continued on their originally-assigned ALX-0061 IV dose (8 patients in 1 mg/kg
arm, 8 patients in 3 mg/kg arm, and 8 patients in 6 mg/kg arm), 4 patients
changed their dosing regimen, and 3 patients switched from PBO to ALX-0061.
 This post-hoc analysis utilised data from patients whose originally assigned ALX-0061
ALX-0061 was assessed in a Phase I/II study in patients with active RA on stable MTX
therapy (1).
Study Design of the Phase I/II Clinical Trial
Phase I – Single ascending dose
ALX-0061 0.3mg/kg
treatment with ALX-0061 was also assessed.
Methods
 Clinical remission was defined by both DAS28 (CRP) <2.6 and the ACR/EULAR
Boolean-based definitions.
 Maintenance of remission was defined as being in remission at consecutive time
points (i.e. at weeks 16, 20, and 24 , or at weeks 12, 16, 20, and 24 ).
 Patient functional status was assessed using the Health Assessment Questionnaire
(HAQ) with HAQ < 0.5 defining normal physical function. An improvement in HAQ
score > 0.25 was considered to be clinically meaningful.
Patient
population:
patients
with
active RA
on stable
MTX regimen
Randomisation (n=28)
purpose of this post-hoc analysis was to assess the induction and maintenance of
remission during ALX-0061 treatment.
 In addition, the impact of disease remission on physical function following 24-week
ALX-0061 1mg/kg
ALX-0061 3mg/kg
ALX-0061 6mg/kg
Placebo
50
40
29,2
25
20
80
60
47.1
40
22,2
20
0
0
DAS28(CRP) <2.6
DAS28 (CRP) <2.6
Boolean
 At week 12 and 24, 50% (12/24) and 62.5% (15/24) of patients treated with ALX-0061

achieved DAS28(CRP)<2.6 remission, respectively.
Remission using the more stringent Boolean criteria was observed in 25% (6/24) and in
29.2% (7/24) of the patients at weeks 12 and 24, respectively.
ALX-0061 IV Induces Sustained Remission in Patients with RA
ALX-0061 1mg/kg Q4W
unmodified (8)
ALX-0061 3mg/kg Q4W
modified (1)
ALX-0061 3mg/kg
Q4W
ALX-0061 3mg/kg Q4W
unmodified (8)
ALX-0061 6mg/kg Q4W
modified (2)
ALX-0061 6mg/kg Q8W
Remission at Wk 16, 20 and 24
unmodified (8)
ALX-0061 6mg/kg Q4W
modified (1)
Placebo
placebo (3)
Placebo
ALX-0061 3mg/kg Q4W
Modification for patients with insufficient EULAR
response
No Remission
 More patients in DAS28 (CRP) remission at week 24 achieved normal physical function

(86.7% vs. 22.2%) compared to patients not in remission.
Moreover, normal physical function was observed in 100% (7/7) of patients in Boolean
remission at week 24.
Conclusions
 This post-hoc analysis showed that in patients with established RA, ALX-0061
100
ALX-0061 1mg/kg
Q4W
ALX-0061 6mg/kg
Q8W
Boolean
Maintenace of Remission at Consecutive Time Points
Phase II – Multiple ascending dose
24/28 of patients continued their original assigned ALX-0061 IV dose
Nanobody® is a registered trademark of Ablynx nv
62,5
60
100
86,7
Remission
 The safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of
 Since remission is the recommended treatment target in the management of RA, the
Week 24
80
dose remained unmodified.
Objectives
100
Week 12
• In the second 12 weeks period, patients with insufficient EULAR response had the
Small (1/10 size of a mAb)
Flexible formatting
controlled, dose escalation, Phase I/II study (1).
received PBO (n=6) or ALX-0061 IV (n=31) at 1 or 3 mg/kg Q4W, or 6 mg/kg Q8W.
Patients received stable doses of MTX ranging from 10-25 mg/week.
CH2
Normal Physical Function in Patients with or without Remission at Week 24
100
Percentage of Patients
VHH
CH1
CL
Normal Physical Function is Regained after Controlling Disease Activity
Remission at Week 12 & Week 24
Percentage of Patients
VHH
 Data were obtained from the multi-center, randomised, double-blind, placebo (PBO)
Randomisation (n=37)
 Ablynx’s Nanobodies
ALX-0061 Induces Remission in Patients with RA
Percentage of Patients
Methods (cont’d)
Background: ALX-0061: IL-6R targeting Nanobody
80
Remission at Wk 12, 16, 20 and 24
 Maintenance of remission during the last 3 (at weeks 16, 20, and 24) and even the
60
last 4 (at weeks 12, 16, 20, and 24) consecutive time points is possible.
40
37,5
 Control of disease activity, as determined by remission, is also important in regaining
29,2
20,8
20
16,7
DAS28 (CRP) <2.6
Boolean
 Looking at maintenance of remission, approximately one third, i.e. 37.5% and 29.2%, of

patients treated with ALX-0061 remained in DAS28 remission during the last 3 (at weeks
16, 20, and 24) and last 4 (at weeks 12, 16, 20, and 24) consecutive time points, resp.
Maintenance of remission based on the Boolean criteria was also observed, being 20.8%
and 16.7% of the patients for the last 3 or 4 successive time points.
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normal physical function.
 These results are indicative of a strong potential for disease modifying activity of
0
switched (3)
induced and maintained remission as assessed by both DAS28 (CRP) and the more
stringent Boolean remission definition.
ALX-0061 supporting treat-to-target management of RA as reflected in the EULAR
recommendations.
(1) Ann Rheum Dis 2013;72(Suppl3):64
Technologiepark 21, 9052 Zwijnaarde, Belgium

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