Clinical Trials

Date: 2017-09-11

Type of information: Results

phase: 2

Announcement: results

Company: Abbvie (USA - IL)

Product: upadacitinib (ABT-494)

Action mechanism:

• JAK inhibitor/tyrosine kinase inhibitor. Upadacitinib is an investigational oral agent engineered to selectively inhibit JAK1, which plays an important role in the pathophysiology of immune-mediated disorders. It has been discovered and developed by AbbVie.

Disease: rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Argentina, Brazil, Bulgaria, Colombia, Czech Republic Denmark,Hong Kong,Italy,Norway,Slovenia

Trial details:

• SELECT-BEYOND is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of two once-daily doses (15 mg and 30 mg) of upadacitinib in adult patients with moderate to severe rheumatoid arthritis who are on a stable dose of conventional synthetic DMARDs (csDMARDs) and have had an inadequate response or intolerance to bDMARDs. The primary endpoints included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 12 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50 and ACR70 response at week 12. More information on this trial can be found at www.clinicaltrials.gov (NCT02706847). The  SELECT Phase 3 RA program evaluates more than 4,000 patients with moderate to severe rheumatoid arthritis in six studies. The studies include assessments of efficacy, safety and tolerability across multiple rheumatoid arthritis patient populations. Key measures of efficacy evaluated include ACR responses, disease activity and inhibition of radiographic progression. (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951, NCT02675426).

Latest news:

• • On September 11, 2017, AbbVie announced positive top-line results from the Phase 3 SELECT-BEYOND clinical trial evaluating upadacitinib (ABT-494) in patients with moderate to severe rheumatoid arthritis (RA) who did not adequately respond or were intolerant to treatment with biologic DMARDs (bDMARDs). Results showed that after 12 weeks of treatment, both once-daily doses of upadacitinib (15 mg and 30 mg) met the study's primary endpoints of ACR20* and low disease activity (LDA). All ranked secondary endpoints were also achieved with both doses.
• Results at week 12 showed that of patients receiving an oral once-daily dose of 15 mg or 30 mg upadacitinib, ACR20/50/70* response was achieved in 65/34/12 percent of patients with the 15 mg dose, respectively, and 56/36/23 percent with the 30 mg dose, respectively, compared to 28/12/7 percent in the placebo group.1 These results were statistically significant compared to placebo (p<0.001) for all comparisons except ACR70 for the 15 mg dose.1
• Additionally, a significantly higher proportion of upadacitinib patients in both doses achieved LDA and clinical remission targets at week 12 compared to patients receiving placebo (p<0.001).1 Low disease activity was achieved by 43 percent and 42 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 14 percent of patients receiving placebo.1 Clinical remission was achieved by 29 percent and 24 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 10 percent of patients receiving placebo.1
• Results continued to be encouraging through week 24.1 Of patients treated with upadacitinib from study entry, ACR20/50/70* response was achieved in 62/43/22 percent of patients with the 15 mg dose and 59/43/24 percent with the 30 mg dose at week 24. Low disease activity was achieved by 52 percent of patients receiving either dose of upadacitinib. Clinical remission was achieved by 32 percent and 35 percent of patients in the 15 mg and 30 mg groups, respectively.1Comparisons to placebo cannot be made at week 24, since all placebo patients received either upadacitinib 15 mg or 30 mg beginning at week 12.

• 		Week 12		Week 24
  	Placebo  (PBO)  (n=169)	Upadacitinib  15 mg (n=164)	Upadacitinib  30 mg (n=165)	Upadacitinib  15 mg (n=164)	Upadacitinib  30 mg (n=165)
  ACR20*	28%	65%	56%	62%	59%
  ACR50*	12%	34%	36%	43%	43%
  ACR70*	7%	12%	23%	22%	24%
  LDA**	14%	43%	42%	52%	52%
  Clinical  Remission***	10%	29%	24%	32%	35%

  All week 12 endpoints shown in the table achieved p-values of <0.001 versus placebo for both doses except for the 15 mg ACR70 value. ACR50 and ACR70 were not ranked secondary endpoints. Not all ranked and non-ranked secondary endpoints shown. Statistical comparisons to placebo were not conducted for week 24 values since no patients received placebo beyond week 12. Data for week 24 only shown for patients treated with upadacitinib from study entry.

  *ACR20/50/70 is defined as American College of Rheumatology 20 percent/50 percent/70 percent improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.

  **LDA was defined by a clinical response Disease Activity Score with 28 joint counts (C-reactive protein) (DAS28 [CRP]) less than or equal to 3.2

  ***Clinical remission was based on DAS28 (CRP) less than 2.6.

• All week 12 endpoints shown in the table achieved p-values of <0.001 versus placebo for both doses except for the 15 mg ACR70 value. ACR50 and ACR70 were not ranked secondary endpoints. Not all ranked and non-ranked secondary endpoints shown. Statistical comparisons to placebo were not conducted for week 24 values since no patients received placebo beyond week 12. Data for week 24 only shown for patients treated with upadacitinib from study entry.
• *ACR20/50/70 is defined as American College of Rheumatology 20 percent/50 percent/70 percent improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.
• **LDA was defined by a clinical response Disease Activity Score with 28 joint counts (C-reactive protein) (DAS28 [CRP]) less than or equal to 3.2
• ***Clinical remission was based on DAS28 (CRP) less than 2.6.
• In this study, the safety profile of upadacitinib was consistent with previously reported Phase 2 trials and the Phase 3 SELECT-NEXT clinical trial. No new safety signals were detected. During the placebo-controlled period, serious adverse events occurred in 5/7/0 percent of patients in the 15 mg/30 mg/placebo groups, respectively. There were two deaths reported during the study.1One was a patient in the 15 mg dose group with cause of death unknown. The second was a patient in the 30 mg dose group who presented with fever and diarrhea, subsequent heart failure and presumed pulmonary embolism (PE) during hospitalization. Inclusive of the case mentioned above, a total of two cases of PE and no deep vein thrombosis (DVT) were reported during the placebo-controlled period. In the previously reported Phase 3 SELECT-NEXT trial, no cases of DVT or PE occurred.15 Across the SELECT RA program, including both, the placebo-controlled and extension periods, the rate of DVT and PE remains consistent with the background rate for the RA patient population.

 

Is general: Yes