Risankizumab vs Adalimumab for Juvenile Psoriatic Arthritis

(KnaPsAck Trial)

Recruiting at30 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Must not be taking: Anti-TNF, IL-23 inhibitors

Disqualifiers: Other autoimmune diseases, Rheumatic diseases, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Psoriatic arthritis (PsA) is a type of arthritis that happens when the body's immune system attacks healthy cells and tissues causing joint pain, stiffness, and swelling. Symptoms can get worse and go away for periods of time. PsA that begins before a patient's 16th birthday is called juvenile PsA (jPsA).This study will evaluate how safe risankizumab is for the treatment of psoriatic arthritis and to assess change in disease symptoms. Risankizumab is being studied for the treatment of jPsA and adalimumab is approved for the treatment of jPsA. Participants are placed in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 4 chance that participants will be assigned to receive adalimumab. Approximately 40 juvenile participants with jPsA will be enrolled at approximately 30 sites worldwide. Participants will receive risankizumab and adalimumab as subcutaneous (SC) injections based on body weight. At the start of Period 1, participants are randomized to receive risankizumab or adalimumab for 24 weeks. Participants who respond to the study treatment received in Period 1, will continue to receive the same treatment in Period 2 for another 100 weeks. Those with worsening jPsA symptoms in Period 2 will be withdrawn from the study. Participants who receive adalimumab are followed for safety for 70 days after the last study treatment. Participants who receive risankizumab are followed for 140 days after the last study treatment. There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have had an inadequate response or intolerance to certain medications, which might imply that you can continue with them if they are not effective. It's best to discuss this with the trial coordinators.

Is Adalimumab safe for children with juvenile arthritis?

Adalimumab has been studied for safety in children with various forms of juvenile arthritis, psoriasis, and Crohn's disease, showing it is generally safe for long-term use in these conditions. ^{1 2 3 4 5}

How does the drug Risankizumab differ from other treatments for juvenile psoriatic arthritis?

Risankizumab is unique because it specifically targets and inhibits interleukin-23 (IL-23), a protein involved in inflammation, which is different from other treatments that may target different pathways. This mechanism of action is novel compared to traditional therapies for psoriatic arthritis. ^{6 7 8 9 10}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for children with juvenile Psoriatic Arthritis (jPsA) who have had it for at least 6 months, are experiencing active disease in three or more joints, and haven't responded well to treatments like methotrexate. Kids can't join if they meet certain medical conditions that the study outlines.

Inclusion Criteria

I have active disease in 3 or more joints.

My previous treatment for at least 2 months did not work.

I have been diagnosed with juvenile psoriatic arthritis for at least 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants are randomized to receive risankizumab or adalimumab for 24 weeks

24 weeks

Regular visits at a hospital or clinic

Treatment Period 2

Participants who respond to the treatment in Period 1 continue the same treatment for another 100 weeks

100 weeks

Regular visits at a hospital or clinic

Follow-up for Adalimumab

Participants who receive adalimumab are followed for safety for 70 days after the last study treatment

10 weeks

Follow-up for Risankizumab

Participants who receive risankizumab are followed for safety for 140 days after the last study treatment

20 weeks

Treatment Details

Interventions

• Adalimumab (Monoclonal Antibodies)
• Risankizumab (Monoclonal Antibodies)

Trial Overview The trial is testing Risankizumab against Adalimumab, both given as injections based on body weight. Participants will be randomly assigned to one of these drugs for an initial period of 24 weeks and may continue up to another 100 weeks depending on their response.

Participant Groups

Group I: Risankizumab Experimental Treatment 1 Intervention

Participants will receive risankizumab for 24 weeks, in Period 1. Participants who respond to the study treatment received in Period 1, will continue to receive the same treatment in Period 2 for another 100 weeks. There will be a 140 day safety follow up after the treatment period.

Group II: Adalimumab Experimental Treatment 1 Intervention

Participants will receive adalimumab for 24 weeks, in Period 1. Participants who respond to the study treatment received in Period 1, will continue to receive the same treatment in Period 2 for another 100 weeks. There will be a 70 day safety follow up after the treatment period.

Adalimumab is already approved in Canada, Japan for the following indications:

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a 24-week study involving 356 patients with juvenile idiopathic arthritis (JIA), adalimumab demonstrated good safety, with an overall adverse drug reaction (ADR) rate of 29.8% and serious ADRs at 3.4%.

The effectiveness of adalimumab was notable, with the remission rate improving from 21.7% at baseline to 74.7% by week 24, indicating significant therapeutic benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of adalimumab in Japanese patients with juvenile idiopathic arthritis: Results from a real-world postmarketing study. Takei, S., Iwata, N., Kobayashi, I., et al.[2022]

Adalimumab demonstrated long-term safety and efficacy in treating juvenile idiopathic arthritis (JIA) over 6 years, with significant clinical responses observed in 66% to 96% of patients achieving various levels of improvement by week 104.

The treatment was well tolerated, with only 12 serious infections reported among 171 patients over 592.8 patient-years, and no severe adverse events like heart failure or malignancies, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate. Lovell, DJ., Brunner, HI., Reiff, AO., et al.[2021]

In a study involving 577 pediatric patients across various conditions, adalimumab was found to have a generally safe profile, with common adverse events including upper respiratory infections and headaches, but no new safety concerns were identified.

Serious infections occurred at a rate of 4.0 events per 100 patient-years, with pneumonia being the most frequent serious adverse event, indicating that while serious infections are a risk, they are relatively infrequent in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. Horneff, G., Seyger, MMB., Arikan, D., et al.[2019]

In a study involving 838 patients with polyarticular-course juvenile idiopathic arthritis, adalimumab (ADA) was found to be well tolerated, with no deaths or malignancies reported over a 7-year period.

Patients starting treatment with ADA ± methotrexate showed a trend towards lower disease activity compared to those on methotrexate alone, suggesting ADA may be more effective in managing symptoms in the first year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Adalimumab in Patients With Polyarticular Course of Juvenile Idiopathic Arthritis: STRIVE Registry Seven-Year Interim Results. Brunner, HI., Nanda, K., Toth, M., et al.[2020]

In juvenile idiopathic arthritis (JIA) patients starting adalimumab therapy, anti-adalimumab antibody (AAA) production significantly increased starting at 3 months, with 34% of patients developing AAA by that time.

Risk factors for developing AAA included being female, having an elevated ESR, and using leflunomide, while the use of methotrexate was found to be protective against AAA development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching. Brunelli, JB., Silva, CA., Pasoto, SG., et al.[2022]

In the phase 3 KEEPsAKE 2 trial involving 444 patients with psoriatic arthritis, risankizumab significantly improved disease outcomes compared to placebo, with 51.3% of patients achieving at least a 20% improvement in their symptoms by week 24.

Risankizumab was well tolerated, with similar rates of serious adverse events (4.0% for risankizumab vs. 5.5% for placebo) and lower rates of serious infections compared to placebo, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Östör, A., Van den Bosch, F., Papp, K., et al.[2022]

Risankizumab is the first targeted interleukin-23 inhibitor approved for moderate-to-severe Crohn's disease, showing promising efficacy and a favorable safety profile in clinical trials involving both treatment-naïve and previously treated patients.

The specific mechanism of action of Risankizumab, which selectively inhibits IL-23, may offer enhanced efficacy and safety compared to broader IL-12/23 inhibitors, with ongoing trials exploring this potential advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab to treat moderately to severely active Crohn's disease in adults: an evaluation of trials and data. Johnson, AM., Loftus, EV.[2023]

Risankizumab-rzaa (Skyrizi®) is an effective treatment for moderate-to-severe psoriasis, as demonstrated in four pivotal Phase III trials involving adult patients, showing both efficacy and safety.

The drug works by targeting interleukin-23p19 (IL-23p19), a key player in the inflammatory process of psoriasis, which helps reduce the symptoms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis. Reddy, V., Yang, EJ., Myers, B., et al.[2020]

Risankizumab is a monoclonal antibody that effectively targets IL-23, showing superior efficacy compared to placebo and other treatments like ustekinumab and adalimumab in pivotal phase III trials involving adults with moderate to severe plaque psoriasis.

In long-term studies, risankizumab demonstrated durable efficacy and improved quality of life for patients, with a favorable safety profile over more than 2.5 years of continuous treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab: A Review in Moderate to Severe Plaque Psoriasis. Blair, HA.[2021]

Risankizumab, a monoclonal antibody targeting IL-23, received its first global approval in March 2019 in Japan for treating various forms of psoriasis, including psoriasis vulgaris and psoriatic arthritis.

The drug is currently approved in multiple regions, including the USA and EU, for moderate-to-severe plaque psoriasis and is undergoing further clinical trials for other conditions like Crohn's disease and ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab: First Global Approval. McKeage, K., Duggan, S.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of adalimumab in Japanese patients with juvenile idiopathic arthritis: Results from a real-world postmarketing study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Adalimumab in Patients With Polyarticular Course of Juvenile Idiopathic Arthritis: STRIVE Registry Seven-Year Interim Results. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Risankizumab to treat moderately to severely active Crohn's disease in adults: an evaluation of trials and data. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Risankizumab: A Review in Moderate to Severe Plaque Psoriasis. [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Risankizumab: First Global Approval. [2020]