Background/Purpose: NNC0109-0012 (anti-IL-20 mAb) is a novel human monoclonal IgG₄ antibody which binds to and neutralizes the activity of IL-20. Data from a phase 1 single-dose trial in healthy volunteers and RA patients, and a multiple-dose trial in RA patients, did not raise any safety concerns. NNC0109-0012 has linear pharmacokinetics in the investigated dose range (1-3 mg/kg) and signs of reduced disease activity were shown in RA patients. Objectives of this phase 2a trial were to evaluate changes in disease activity in RA patients with active disease using the following endpoints: DAS28-CRP, ACR20/50/70, and the patient-reported outcomes physical function (HAQ-DI), pain (Pain VAS) and global disease activity (PtGA VAS) after 12 weeks of treatment and during a 13-week follow up period.

Methods: A total of 67 RA patients (51 females:16 males) with active disease (DAS28 (CRP) >4.5, ≥5 swollen and ≥5 tender joints) were randomized in a 2:1 ratio (45 NNC0109-0012: 22 placebo) in a multicenter, double-blind, placebo-controlled, parallel group trial. Patients were dosed once-weekly s.c. with 3 mg/kg NNC0109-0012 or placebo for 12 weeks and followed for an additional 13 weeks. Patients were 18 to 75 years old with active RA and on stable methotrexate (MTX) treatment (>7.5 to <25 mg/week for at least 4 weeks). The primary endpoint was change in DAS28 (CRP) at Week 12.

Results: DAS28 (CRP) was significantly decreased compared to placebo at Weeks 12 and 16, and through Weeks 12 – 25 for seropositive (RF and anti-CCP positive) patients (n=29 and 14; 3 mg/kg and placebo, respectively). Significantly more NNC0109-0012 treated seropositive patients compared to placebo achieved ACR20/50 at Week 12 and ACR70 at Weeks 12, 16 and 20. Physical function, pain and global disease activity were significantly improved compared to placebo for seropositive patients for Weeks 12 – 25. Similar trends in NNC0109-0012 effects on most of the secondary endpoints for disease activity were observed in all randomized patients, although not all changes were significant. No deaths, serious adverse events or dose limiting toxicities were reported.

 

	Week 12	Week 16	Week 20	Week 25
DAS28 (CRP)a	-0.88*	-0.72*	-0.51	-0.60
DAS28 (CRP), S+	-1.66†	-1.55†	-1.26**	-1.24**
ACR20 (%), S+	58.6/21.4*	62.1/35.7	58.6/28.6*	58.6/35.7
ACR50 (%), S+	48.3/14.3*	44.8/14.3	44.8/21.4	44.8/21.4
ACR70 (%), S+	34.5/0*	34.5/0*	31.0/0*	31.0/7.1
HAQ-DI, S+	-0.45*	-0.32	-0.42*	-0.47*
Pain (VAS), S+	-30†	-28**	-25**	-29†
PtGA (VAS), S+	-28†	-29†	-25**	-28†
DAS28 (CRP), HAQ-DI, pain (VAS), PtGA (VAS) shown as mean difference for NNC0109-0012 ˗ placebo; Proportion with ACR20/50/70 for NNC or placebo shown as NNC/placebo.             VAS = visual analogue scale (mm).  aAll randomized patients ;                                  S+=seropositive ; * = p<0.05, ** = p<0.01,†= p<0.001

 Conclusion: This phase 2a trial investigating NNC0109-0012 (anti-IL-20 mAb) in patients with RA met its primary endpoint, showing significant improvement in DAS28 (CRP) after 12 weeks. For the sub-group of RF/anti-CCP-positive patients, the treatment effects of NNC0109-0012 on all disease parameters were significantly larger than for all randomized patients at week 12 and were sustained during the 13 weeks after stopping study drug administration. Treatment with NNC0109-0012 revealed no safety concerns. The data from this trial support further clinical development of NNC0109-0012 (anti-IL-20 mAb) in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-responses-and-patient-reported-outcomes-to-nnc0109-0012-anti-il-20-mab-in-rheumatoid-arthritis-ra-patients-following-12-weeks-dosing-and-13-weeks-follow-up-results-from-a-phase-2a/