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

Study Purpose

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 after. 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 its prescription and many patients may have limited access to these treatments. The best treatment strategy for PsO that takes into account efficacy and cost effectiveness is unknown. For instance, whether some PsO patients can stop biological treatment and be treated 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 of these mechanisms in maintaining remission and relapses will advance the development of biomarkers that eventually guide development of best treatment strategies for PsO. Secukinumab targets interleukin (IL)-17a and is highly efficacious in the treatment of plague PsO with a favorable safety profile. Some patients may have the response maintained after withdrawal of secukinumab. With the proven efficacies, sustainability after withdrawal and safety profile, secukinumab could be a choice of initial treatment for patients with moderate to severe PsO. Secukinumab has been recommended as first line treatment for selected patients with moderate to severe PsO by the American Academy of Dermatology and the European S3 guidelines. However, the use of biologics as first line is limited by cost issue. Overall, real-life data on biologic treatment for moderate to severe PsO is scanty.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 22 Years - 90 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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.

Exclusion Criteria:

  • - 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 excl

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04239859
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Singapore General Hospital
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Ying Ying Leung, MD
Principal Investigator Affiliation Singapore General Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries Singapore
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Plaque Psoriasis
Additional Details

First, the investigators hypothesize that a proportion of participants with moderate to severe PsO may sustain good outcomes when a short course of secukinumab is withdrawn. Second, the investigators hypothesize that they can identify the perturbations in the architecture of the immunome which are pathogenic, and to discriminate such perturbations based on treatment and clinical responses, thus distilling therapeutics and diagnostics signatures. Therefore, the objectives of this study are as follow: Specific aim 1: To describe the clinical course, sustained good outcomes, relapse rate, time to relapse and quality of life in PsO participants who stopped a 6-month short course treatment of secukinumab, till the end of 2-years. Specific aim 2: To identify the genomic and immunomics signatures in skin biopsies and blood in PsO participants who has good outcomes (PASI 75) at 6 months, comparing treatment vs.#46; pragmatic control. Specific aim 3: To identify the genomic and immunomics signatures in skin biopsies and blood in PsO participants who sustained good outcomes at 1 year after stopping secukinumab, compared to those relapsed.

Arms & Interventions

Arms

Experimental: Secukinumab

Participants will be offered secukinumab as first-line systemic treatment for moderate to severe PsO. The indication for secukinumab will be equivalent to current registered indications. Standard dose of subcutaneous secukinumab for moderate to severe PsO will be given at 300 mg at weeks 0, 1, 2, 3, and 4, then monthly thereafter, for a total duration of 6 months. secukinumab will be withdrawn after 6 months. For some participants, there may be relapse of PsO. Relapses will be managed as per standard care.

Active Comparator: Standard Care

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.

Interventions

Biological: - secukinumab

Secukinumab for 6 months, given at weeks 0, 1, 2, 3 and 4, then monthly till 6 months. 300mg per administration, subcutaneously.

Drug: - Methotrexate

Oral tablet up to 15mg per week

Drug: - Cyclosporin A

Oral capsule up to 200mg per day

Drug: - Acitretin

Oral capsule up to 25mg per day

Contact a Trial Team

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International Sites

Singapore General Hospital, Outram Park, Singapore

Status

Address

Singapore General Hospital

Outram Park, , 169608

Site Contact

Ying Ying A/Prof Leung

[email protected]

+65 63265276

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