ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1202

A Phase 2A, Placebo-Controlled, Randomized Study of ABT-981, an Anti-Interleukin-1Alpha and -1Beta Dual Variable Domain Immunoglobulin, to Treat Erosive Hand Osteoarthritis

Margreet Kloppenburg1, Charles Peterfy2, Ida K. Haugen3, Féline Kroon4, Su Chen5, Li Wang5, Wei Liu5, Gwen Levy5, Roy Fleischmann6, Francis Berenbaum7, Désirée van der Heijde4, Jeroen K. Medema5 and Marc C. Levesque5, 1Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 2Spire Sciences, Inc., Boca Raton, FL, 3Diakonhjemmet Hospital, Oslo, Norway, 4Leiden University Medical Center, Leiden, Netherlands, 5AbbVie Inc., North Chicago, IL, 6University of Texas Southwestern Medical Center at Dallas, Metroplex Clinical Research Center, Dallas, TX, 7University Pierre & Marie Curie and Inserm, DHU i2B, APHP, Hospital Saint-Antoine, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords:

Session Information

Date: Monday, November 6, 2017

Title: Osteoarthritis – Clinical Aspects Poster I: Clinical Trials and Interventions

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: No approved OA therapies reduce pain and slow joint damage. Mouse data suggested that inhibiting IL-1α and -1β with ABT-981 would reduce pain and slow structural progression in EHOA. This study tested the efficacy and safety of ABT-981 in EHOA.

Methods: Subjects with HOA per ACR criteria, ≥3 inflamed IP joints (tender, swollen, or both), hand pain ≥6 (scale 0–10), and ≥1 erosive IP joint on X-ray (Verbruggen-Veys) were randomized to placebo (PBO) or ABT-981 200 mg SC every 2 wk for 26 wk. The primary outcome was AUSCAN hand pain at 16 wk. Subjects had radiographs of both hands and MRI of the index hand at baseline and 26 wk. Both radiographs (Verbruggen-Veys, GUSS™, OARSI, Kellgren-Lawrence [KL]) and MRIs (HOAMRIS) were read by 2 independent central readers. A modified intent-to-treat population (ie, randomized and treated) was analyzed. Continuous efficacy endpoints were assessed using ANCOVA models with treatment and country as main factors and baseline measurements as covariates with LOCF imputation for the primary endpoint.

Results: Of 131 treated subjects (85% women; mean age 66 y), 61/67 randomized to PBO and 49/64 to ABT-981 completed the study; subject characteristics were well matched. AUSCAN pain was not significantly different vs PBO at wk 16 (P=.39; Table 1, Figure); X-ray data and other endpoints also were not statistically different vs PBO (Table 1). ABT-981 significantly decreased hsCRP, neutrophils, IL-1α, and IL-1β. Immunogenicity had no impact on ABT-981 pharmacokinetics. Besides injection site reactions and neutropenia, ABT-981 was well tolerated and safety was similar vs PBO, with no serious infections (Table 2).

Conclusion: Despite adequate pharmacodynamics results, targeting IL-1 may be ineffective in EHOA, as ABT-981 did not improve outcomes.

 

Table 1

 

PBO

ABT-981

PBO

ABT-981

P

1° Endpoint

Baseline, Mean±SD

LS Mean Change±SE at Wk 16

AUSCAN pain (0–50)

39±7

38±6

−10.7±2.4

−9.2±2.3

.39

2° Endpoints

Baseline, Mean±SD

LS Mean Change±SE at Wk 26

AUSCAN function (0–90)

69±15

71±13

−14.3±4.2

−16.4±4.0

.49

Tender joints (0–30)

12±6

12±7

−4.7±1.2

−5.8±1.2

.32

Swollen joints (0–30)

6±6

6±5

−1.8±0.8

−2.2±0.9

.64

X-ray erosive joints (0–16)

2±2*

3±2*

0.26±0.08†

0.18±0.08†

.33

KL score (0–80)

41±13

46±13

0.13±0.19

0.10±0.19

.87

OARSI JSN (0–58)

28±10

32±9

0.14±0.19

0.03±0.19

.51

OARSI osteophytes (0–58)

23±11

26±10

0.25±0.15

0.14±0.16

.45

HOAMRIS synovitis (sum score; 0–52.5)

11±4

10±4

0.92±0.48

0.85±0.51

.89

HOAMRIS erosive damage (sum score; 0–105)

18±9

17±10

0.26±0.64

0.10±0.67

.80

HOAMRIS BML (sum score, 0–105)

7±5

5±4

0.11±0.64

0.44±0.66

.60

*Verbruggen-Veys, erosive phase (E) + erosive with remodeling (E/R) or †new E or E/R or R.

 

Table 2

PBO (n=67)

ABT-981 (n=64)

Any AE/serious AE, %

88/3

91/3

Death, %

0

0

Infection/serious infection, %

51/0

41/0

Injection site reaction, %

16

36

Neutropenia by NCI CTCAE grade, n

 

 

     G2 (1000 to <1500/mm3)

0

9

     G3 (500 to <1000/mm3)

0

3

     G4 (<500/mm3)

0

0

 

Disclosure: M. Kloppenburg, Pfizer, 2,AbbVie, GlaxoSmithKline, Merck, Levicept, 5; C. Peterfy, Spire Sciences, Inc, 1,Spire Sciences, Inc, 3,Amgen, 8; I. K. Haugen, Abbvie, 5; F. Kroon, None; S. Chen, Abbvie, 1,Abbvie, 3; L. Wang, AbbVie Inc., 1,AbbVie Inc., 3; W. Liu, AbbVie Inc., 3,AbbVie Inc., 1; G. Levy, AbbVie Inc., 1,AbbVie Inc., 3; R. Fleischmann, AbbVie Inc., 2,AbbVie Inc., 5; F. Berenbaum, AbbVie, Pfizer, Regeneron, 5; D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, 5,Director of Imaging Rheumatology bv., 3; J. K. Medema, AbbVie Inc., 1,AbbVie Inc., 3; M. C. Levesque, AbbVie Inc., 1,AbbVie Inc., 3.

To cite this abstract in AMA style:

Kloppenburg M, Peterfy C, Haugen IK, Kroon F, Chen S, Wang L, Liu W, Levy G, Fleischmann R, Berenbaum F, van der Heijde D, Medema JK, Levesque MC. A Phase 2A, Placebo-Controlled, Randomized Study of ABT-981, an Anti-Interleukin-1Alpha and -1Beta Dual Variable Domain Immunoglobulin, to Treat Erosive Hand Osteoarthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/a-phase-2a-placebo-controlled-randomized-study-of-abt-981-an-anti-interleukin-1alpha-and-1beta-dual-variable-domain-immunoglobulin-to-treat-erosive-hand-osteoarthritis/. Accessed .

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