Outcomes With Treatment and Withdraw of Ixekizumab in Patients With Plaque Psoriasis

NCT04537689 | Recruiting Phase 4 DMC

• 1 other identifier: PsO_IXE
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Psoriasis (PsO) is a systemic immune disease that affect 2-4% of the population worldwide. PsO causes tremendous burden in terms of quality of life, psychological impact, disability and work productivity of affected individuals. PsO is associated with an increased risk of cardiovascular morbidities and mortality in the long term. Up to 30% of PsO patients develop psoriatic arthritis (PsA) over time causing joint deformities and further disabilities. Majority of patients with PsA developed PsO first, and arthritis develop 5-10 years afterwards. PsA and PsO are increasingly recognized as two entities under the umbrella of psoriatic diseases. Advances in biological treatments have greatly improved the prognosis of patients with PsO. Remarkable efficacies have been demonstrated for patients with moderate to severe PsO in randomized controlled trials (RCTs). However, the high cost of biological treatment is one of the major barriers to prescription of biological treatment and many patients may have limited access to these treatments. The best strategy of treatment for PsO that takes into account efficacy and cost effectiveness is unknown. For instance, whether some PsO patients can stop biological treatment and be retreated with non-biologic medications upon relapse, which may enhance cost effectiveness of treatment. Preliminary studies have shown that some PsO patients were able to maintain good control of disease without medications after biologics withdrawal. The patho-immunological mechanisms behind long term remission after drug withdrawal is poorly understood. Better understanding on patho-immunological mechanisms on maintenance of remission and relapses will advance the development of biomarkers that eventually guide development of best treatment strategies for PsO. Ixekizumab is a humanized immunoglobulin G4 (IgG4 kappa) monoclonal antibody targeting interleukin (IL)-17A. It is highly efficacious in the treatment of plague PsO with and favorable safety profile as shown in randomized controlled trials, and is an approved treatment for moderate-to-severe PsO by the U.S. Food and Drug Administration and Health Sciences Authority. With the proven efficacies, ixekizumab could be a choice of first-line treatment for patients with moderate to severe PsO. The 2013 American Academy of Dermatology position statement have stated that the old paradigm of stepwise-therapy starting first with phototherapy and oral systemic therapies before biologic treatment is not required for patients with moderate to severe PsO. In the recent 2017 update of the European S3 guidelines also recommend the use of IL-17 inhibitors as either a first- or second-line agent. In a RCT that evaluated relapses after withdrawal of ixekizumab among patients who achieved a clearance of PsO, loss of PsO clearance were seen after a median of 20 weeks. Response can be successfully recaptured in over 80% of patients with retreatment with ixekizumab, suggesting that the treatment regimen could be interrupted in some patients. However, real-life data on biologic treatment or withdrawal for moderate to severe PsO is scatty.

Conditions

Plaque Psoriasis

Outcome Measures

Primary Outcomes (1)

• Proportion of ixekizumab treated PsO participants free of relapse after ixekizumab withdrawal

  The investigators will describe the proportion of ixekizumab treated PsO participants free of relapse at 12 months after ixekizumab withdrawal.

  12 months from ixekizumab withdrawal or 18 months from baseline.

Secondary Outcomes (21)

• Proportion of ixekizumab treated PsO participants free of relapse after ixekizumab withdrawal

  15, 18, and 24 months from ixekizumab withdrawal or 21, 24, and 30 months from baseline.

• Proportion of participants achieving PASI 50

  3 months and 6 months

• Proportion of participants achieving PASI 75

  3 months and 6 months

• Proportion of participants achieving PASI 90

  3 months and 6 months

• Proportion of participants achieving clearance

  3 months and 6 months

Study Arms (2)

Ixekizumab

EXPERIMENTAL

Participants will be offered ixekizumab as first-line systemic treatment for moderate to severe PsO. The indication for ixekizumab will be equivalent to current registered indications. Standard dose of subcutaneous ixekizumab for moderate to severe PsO will be given at 160 mg at week 0, followed by ixekizumab 80mg at weeks 2, 4, 6, 8, 10 and 12, then 4 weekly thereafter, for a total duration of 6 months. Ixekizumab will be withdrawn after 6 months. For some participants, there may be relapse of PsO. Relapses will be managed as per standard care.

Biological: Ixekizumab

Standard Care

ACTIVE COMPARATOR

The management of PsO in the control arm will be the same as that in the standard care. The standard care for moderate to severe PsO in Singapore is to start either phototherapy, methotrexate, acitretin or cyclosporin A.

Drug: Methotrexate; Drug: Cyclosporin A; Drug: Acitretin

Interventions

Ixekizumab BIOLOGICAL

Ixekizumab for 6 months, given 160mg at weeks 0, followed by 80mg at 2, 4, 6, 8, 10 and 12, then 4 weekly till 6 months. Given subcutaneously.

Ixekizumab

Methotrexate DRUG

Oral tablet up to 15mg per week

Standard Care

Cyclosporin A DRUG

Oral capsule up to 200mg per day

Standard Care

Acitretin DRUG

Oral capsule up to 25mg per day

Standard Care

Eligibility Criteria

• Age: 22 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (\>21-year-old).
• Diagnosed by dermatologist as plague-type PsO.
• Having moderate to severe plague-type PsO as defined by the following:
• Psoriasis Area and Severity Index (PASI) ≥12/72,
• And, investigator Global Assessment Score (IGA) ≥3,
• And, PsO involving body surface area involvement (BSA) ≥10%
• And Candidate for phototherapy and/or systemic therapy
• Topical corticosteroid up to moderate potencies are allowed
• Able to provide informed consent.

You may not qualify if:

• Forms of PsO other than plaque-type.
• Evidence of skin conditions at the time of the screening visit (e.g. eczema) that would interfere with evaluation of the effect of the investigational product on PsO.
• Evidence of active tuberculosis or other active infections (like Hepatitis C/B), malignancy; active or known use of other immunosuppressive drugs (eg. AIDS, rheumatoid arthritis, organ rejection etc) at the screening visit.
• Previous exposure to any systemic immunosuppressants (eg. methotrexate) or phototherapy
• History or current signs of a severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances.
• Having current or history of malignancy, except non-melanoma skin cancer, within the previous 5 years that have been adequately treated.
• History of inflammatory bowel disease.
• Pregnancy or lactating mothers.
• As treatment regimen is different, participants with evidence of PsA will be excluded

Sponsors & Collaborators

• Singapore General Hospital: lead
• Translational Immunology Institute: collaborator

Study Sites (1)

Singapore General Hospital

Outram Park, 169608, Singapore

RECRUITING

MeSH Terms

Interventions

ixekizumab; Methotrexate; Cyclosporine; Acitretin

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Ying Ying Leung, MD

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Ying Leung, MD

CONTACT

+65 63265276; katy.leung.y.y@singhealth.com.sg

Cynthia Ong, Bachelor

CONTACT

+65 65762609; cynthia.ong.s.q@sgh.com.sg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To evaluate the real-life effectiveness of ixekizumab as first-line systemic treatment in participants with moderate to severe PsO, the investigators would recruit a pragmatic control arm. ⦁ Intervention arm: Eligible participants will be offered ixekizumab as first-line systemic treatment for PsO. Standard dose of subcutaneous ixekizumab for moderate to severe PsO will be given at 160 mg at week 0, followed by ixekizumab 80mg at weeks 2, 4, 6, 8, 10 and 12, then 4 weekly thereafter, for a total duration of 6 months. Ixekizumab will be withdrawn after 6 months. For some participants, there may be relapse of PsO. Relapses will be managed as per standard care. ⦁ Pragmatic control arm Eligible participants will be recruited to pragmatic control arm in these circumstances: * Patient disagree to ixekizumab for personal reasons. * The quota for ixekizumab is exhausted. * The management of PsO in this pragmatic control arm will be the same as that in the standard care.

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 3, 2020
• Study Start: December 10, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 25, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)