Plaque PsoriasisPhase 4NCT04537689
Outcomes With Treatment and Withdraw of Ixekizumab in Patients With Plaque Psoriasis
A Phase 4 study testing Ixekizumab, Methotrexate and Cyclosporin A in people with Plaque Psoriasis, run by Singapore General Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 90 years
- Conditions the study is for
- Plaque Psoriasis
- What is being tested?
- Ixekizumab, Methotrexate and Cyclosporin A
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSingapore
- Study dates
- 10 Dec 2020to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 9Show fewer
- And Candidate for phototherapy and/or systemic therapy
- Topical corticosteroid up to moderate potencies are allowed
- Able to provide informed consent.
Who cannot join
- 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.
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- History of inflammatory bowel disease.
- Pregnancy or lactating mothers.
- As treatment regimen is different, participants with evidence of PsA will be excluded
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
Singapore General Hospital
Outram Park, 169608
Ying Ying Leung, MD, +65 63265276, katy.leung.y.y@singhealth.com.sg
Ying Ying Leung, MD
About this study
Official title: Outcomes With Treatment and Withdraw of Ixekizumab in Patients With Plaque Psoriasis Compared to Standard Care --- a Pragmatic Observational Study
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.
Read more
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.
Read the detailed description
First, the investigators hypothesize that a proportion of patients with moderate to severe PsO may sustain reasonable good outcomes when a short course of ixekizumab is withdrawn.
Second, the investigators hypothesize that the investigators 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 theragnostic signatures.
Therefore, the objectives of the 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 patients who stopped a 6-month short course treatment of ixekizumab, till the end of 2-years.
Specific aim 2: To identify the genomic and immunomic signatures in skin biopsies and blood in PsO patients who has good outcomes (PASI 75) at 6 months, comparing treatment vs pragmatic control.
Specific aim 3: To identify the genomic and immunomic signatures in skin biopsies and blood in PsO patients who sustained good outcomes at 1 year after stopping ixekizumab, compared to those relapsed.
- Conditions
- Plaque Psoriasis
- Being tested
- Ixekizumab, Methotrexate, Cyclosporin A, Acitretin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxekizumabBiological
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.
MethotrexateDrug
Oral tablet up to 15mg per week
Cyclosporin ADrug
Oral capsule up to 200mg per day
AcitretinDrug
Oral capsule up to 25mg per day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Methotrexate; Drug: Cyclosporin A; Drug: Acitretin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The investigators will describe the proportion of ixekizumab treated PsO participants free of relapse at 15, 18, and 24 months after ixekizumab withdrawal.
Measured: 15, 18, and 24 months from ixekizumab withdrawal or 21, 24, and 30 months from baseline.
Proportion of participants achieving PASI 50
Psoriasis is assessed by using the Psoriasis Area Severity Index (PASI) that measures the severity (intensity of redness, thickness and scaling is assessed as none (0), mild (1), moderate (2), severe (3) or very severe (4)) and percentage of affected area in four regions of the body (head and neck, upper limbs, trunk, lower limbs, expressed as nil (0), 1-9% (1), 10-29% (2), 30-49% (3), 50-69% (4), 70-89% (5) or 90-100% (6)). The score ranges from 0 (no psoriasis) to 72 (severe psoriasis). Percentage of improvement of PASI at 3 month and 6 month time points will be calculated from baseline. PASI 50 indicates a 50% improvement of PASI scores.
Measured: 3 months and 6 months
Proportion of participants achieving PASI 75
Psoriasis is assessed by using the Psoriasis Area Severity Index (PASI) that measures the severity (intensity of redness, thickness and scaling is assessed as none (0), mild (1), moderate (2), severe (3) or very severe (4)) and percentage of affected area in four regions of the body (head and neck, upper limbs, trunk, lower limbs, expressed as nil (0), 1-9% (1), 10-29% (2), 30-49% (3), 50-69% (4), 70-89% (5) or 90-100% (6)). The score ranges from 0 (no psoriasis) to 72 (severe psoriasis). Percentage of improvement of PASI at 3 month and 6 month time points will be calculated from baseline. PASI 75 indicates a 75% improvement of PASI scores.
Measured: 3 months and 6 months
Proportion of participants achieving PASI 90
Psoriasis is assessed by using the Psoriasis Area Severity Index (PASI) that measures the severity (intensity of redness, thickness and scaling is assessed as none (0), mild (1), moderate (2), severe (3) or very severe (4)) and percentage of affected area in four regions of the body (head and neck, upper limbs, trunk, lower limbs, expressed as nil (0), 1-9% (1), 10-29% (2), 30-49% (3), 50-69% (4), 70-89% (5) or 90-100% (6)). The score ranges from 0 (no psoriasis) to 72 (severe psoriasis). Percentage of improvement of PASI at 3 month and 6 month time points will be calculated from baseline. PASI 90 indicates a 90% improvement of PASI scores.
Measured: 3 months and 6 months
Proportion of participants achieving clearance
Psoriasis is assessed by using the Psoriasis Area Severity Index (PASI) that measures the severity (intensity of redness, thickness and scaling is assessed as none (0), mild (1), moderate (2), severe (3) or very severe (4)) and percentage of affected area in four regions of the body (head and neck, upper limbs, trunk, lower limbs, expressed as nil (0), 1-9% (1), 10-29% (2), 30-49% (3), 50-69% (4), 70-89% (5) or 90-100% (6)). The score ranges from 0 (no psoriasis) to 72 (severe psoriasis). Percentage of improvement of PASI at 3 month and 6 month time points will be calculated from baseline. Clearance indicates a 100% improvement of PASI scores.
Measured: 3 months and 6 months
Quality of life 1 (EuroQoL-5D-5L)
In all participants (both ixekizumab treated and standard care) the investigators will describe the following:
Every 3-6 monthly till end of 30 months, investigators will evaluate the change scores of Quality of Life (EQ5D-5L). It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions. Each dimension is measured on a scale of 1-5, with '1' indicating no problem, '2' indicating slight problems, '3' indicating moderate problems, '4' indicating severe problems, and '5' indicating unable to/extreme problems. The highest and the lowest scores for both EQ-5D-5L indices were 1.00 (best imaginable health) and -0.769 respectively; where negative values are valued as worse than dead.
EQ VAS records the patient's self-rated health on a vertical visual analogue scale from 0-100 with '0' indicating worst health one can imagine and '100' indicating best health one can imagine.
Measured: 3, 6, 9, 12, 15, 18, 24 and 30 months
Quality of life 2 (Dermatology Life Quality Index - DLQI)
In all participants (both ixekizumab treated and standard care) the investigators will describe the following:
- Questionnaires on health status and quality of life every 3-6 monthly till end of 30 months.
The investigators will evaluate the change scores of Dermatology Life Quality Index (DLQI) at various time points from baseline. DLQI is measured on a scale of 0-3 or not relevant, with '0' indicating not relevant or not at all, '1' indicating a little, '2' indicating a lot, '3' indicating very much. The final score ranges from 0 (minimal effect on quality of life) to 30 (maximum effect on quality of life).
Measured: 3, 6, 9, 12, 15, 18, 24 and 30 months
Quality of life 3 (Hospital Anxiety and Depression Scale - HADS)
n all participants (both ixekizumab treated and standard care) the investigators will describe the following:
- Questionnaires on health status and quality of life every 3-6 monthly till end of 30 months.
The investigators will evaluate the change scores of Hospital Anxiety and Depression Scale (HADS) at various time points from baseline. HADS is a 14 item scale with 7 of the items related to anxiety and the other 7 related to depression. Each item on the questionnaire is scored from 0-3, resulting in anxiety and depression scores each of 0 (no anxiety/depression) to 21 (severe anxiety/depression).
Measured: 3, 6, 9, 12, 15, 18, 24 and 30 months
Patient Global Assessment
In all participants (both ixekizumab treated and standard care) the investigators will describe the following:
- Questionnaires on health status and quality of life every 3-6 monthly till end of 30 months.
The investigators will evaluate the change scores of Patient Global Assessment (0-10) at various time points from baseline, with higher scores meaning worse outcome.
Measured: 3, 6, 9, 12, 15, 18, 24 and 30 months
Patient Acceptable Symptom State (PASS)
In all participants (both ixekizumab treated and standard care) the investigators will describe the following:
- Questionnaires on health status and quality of life every 3-6 monthly till end of 30 months.
The investigators will evaluate the proportion of patient defined acceptable state (acceptable/unacceptable) and whether the symptoms are worse than usual (yes/no) at various time points from baseline.
Measured: 3, 6, 9, 12, 15, 18, 24 and 30 months
Proportion of participants in ixekizumab treatment arm maintaining PASI 50 after ixekizumab withdrawal
For participants in the ixekizumab treatment arm, the investigators describe the following in additional:
- The proportion of participants maintaining PASI 50 at 3, 6, 12, 18 and 24 months after stopping ixekizumab treatment
Measured: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm maintaining PASI 75 after ixekizumab withdrawal
For participants in the ixekizumab treatment arm, the investigators describe the following in additional:
- The proportion of participants maintaining PASI 75 at 3, 6, 12, 18 and 24 months after stopping ixekizumab treatment
Measured: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm maintaining PASI 90 after ixekizumab withdrawal
For participants in the ixekizumab treatment arm, the investigators describe the following in additional:
- The proportion of participants maintaining PASI 90 at 3, 6, 12, 18 and 24 months after stopping ixekizumab treatment
Measured: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm maintaining clearance after ixekizumab withdrawal
For participants in the ixekizumab treatment arm, the investigators describe the following in additional:
- The proportion of participants maintaining PASI clearance at 3, 6, 12, 18 and 24 months after stopping ixekizumab treatment
Measured: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm flaring after ixekizumab withdrawal
For participants in the ixekizumab treatment arm, the investigators describe the following in additional:
- The proportion of participants who flare (defined as losing the PASI50 response) at 3, 6, 12, 18 and 24 months after stopping ixekizumab treatment
Measured: 9, 12, 18, 24 and 30 months from baseline
Histological changes in the skin biopsies of participants in ixekizumab treatment arm who relapsed after ixekizumab withdrawal (or at 18 months if no relapse)
For participants in the ixekizumab treatment arm, the investigators will evaluate the following outcomes at relapse (or at 12 months after stopping ixekizumab if no relapse):
- Histological sections of morphologically psoriasis (lesional) and morphologically no psoriasis (nonlesional) skin biopsies. Skin biopsies at relapse will be scored for the degree of histological improvement compared to that participant's disease at 6 months on a five point scale; -1 (worse) to +3 (excellent).
Measured: Baseline, 6 months, at relapse (or 18 months if no relapse)
Skin genomic profiles in the skin biopsies of participants in ixekizumab treatment arm who relapsed after ixekizumab withdrawal (or at 18 months if no relapse)
For participants in the ixekizumab treatment arm, the investigators will evaluate the following outcomes at relapse (or at 12 months after stopping ixekizumab if no relapse):
- Whole RNA genome transcriptome of the skin biopsies will be studied. The change in transcriptomes at relapse compared to 6-month will be evaluated.
Measured: Baseline, 6 months, at relapse (or 18 months if no relapse)
Peripheral blood immunome profiles of participants in ixekizumab treatment arm who relapsed after ixekizumab withdrawal (or at 18 months if no relapse)
For participants in the ixekizumab treatment arm, the investigators will evaluate the following outcomes at relapse (or at 12 months after stopping ixekizumab if no relapse):
- The B-cell and T-cell subtypes in the peripheral blood will be evaluated using mass cytometry, and compared to that of baseline and 6 months.
- The investigators will evaluate the change in B-cell and T-cell Subtypes at relapse compared to baseline and 6 months.
Measured: Baseline, 6 months, at relapse (or 18 months if no relapse)
Histological changes in the skin biopsies
In all participants, the investigators will evaluate the skin genomic profiles that differentiate between ixekizumab versus standard care control arms.
- Histological sections of morphologically psoriasis (lesional) and morphologically no psoriasis (non lesional) skin biopsies at baseline and 6 months will be examined. Skin biopsies at 6 month will be scored for the degree of histological improvement compared to that participant's baseline disease on a five point scale; -1 (worse) to +3 (excellent).
Measured: Baseline and 6 months
Skin genomic profiles
In all participants, the investigators will evaluate the skin genomic profiles that differentiate between ixekizumab versus standard care control arms.
- Whole RNA genome transcriptome of the skin biopsies will be studied. The change in transcriptomes at 6 months compared to baseline will be evaluated.
Measured: Baseline and 6 months
Peripheral blood immunome profiles
In all participants, the investigators will evaluate the blood immunome profiles that differentiate between ixekizumab versus standard care control arms.
- The B-cell and T-cell subtypes in the peripheral blood of participants in both ixekizumab and standard care arms will be evaluated using mass cytometry. - The investigators will evaluate the change in B-cell and T-cell subtypes at 6 months from baseline for all participants
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start10 Dec 2020
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plaque PsoriasisStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Immunology Institute
- Responsible party
- Sponsor
- Investigators
- Ying Ying Leung, MD, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04537689
- Sponsor's protocol ID
- PsO_IXE
- Status last verified
- Nov 2022
- First submitted
- 28 Aug 2020
- Last updated
- 25 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Outcomes With Treatment and Withdraw of Ixekizumab in Patients With Plaque Psoriasis Compared to Standard Care --- a Pragmatic Observational Study
- ClinicalTrials.gov ID
- NCT04537689
- Acronym / sponsor ID
- PsO_IXE
- Conditions
- Plaque Psoriasis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- Translational Immunology Institute
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 3 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
First, the investigators hypothesize that a proportion of patients with moderate to severe PsO may sustain reasonable good outcomes when a short course of ixekizumab is withdrawn.
Second, the investigators hypothesize that the investigators 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 theragnostic signatures.
Therefore, the objectives of the 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 patients who stopped a 6-month short course treatment of ixekizumab, till the end of 2-years.
Specific aim 2: To identify the genomic and immunomic signatures in skin biopsies and blood in PsO patients who has good outcomes (PASI 75) at 6 months, comparing treatment vs pragmatic control.
Specific aim 3: To identify the genomic and immunomic signatures in skin biopsies and blood in PsO patients who sustained good outcomes at 1 year after stopping ixekizumab, compared to those relapsed.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ixekizumab | Experimental | Biological: IxekizumabParticipants 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. |
| Standard Care | Active comparator | Drug: Methotrexate, Drug: Cyclosporin A, Drug: AcitretinThe 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. |
Who may qualify
- Ages
- 22 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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,
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IxekizumabIxekizumab 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. | Biological | Ixekizumab |
| MethotrexateOral tablet up to 15mg per week | Drug | Standard Care |
| Cyclosporin AOral capsule up to 200mg per day | Drug | Standard Care |
| AcitretinOral capsule up to 25mg per day | Drug | Standard Care |
Primary outcome
Proportion of ixekizumab treated PsO participants free of relapse after ixekizumab withdrawal
Time frame: 12 months from ixekizumab withdrawal or 18 months from baseline.
The investigators will describe the proportion of ixekizumab treated PsO participants free of relapse at 12 months after ixekizumab withdrawal.
21 secondary outcomes
Proportion of ixekizumab treated PsO participants free of relapse after ixekizumab withdrawal
Time frame: 15, 18, and 24 months from ixekizumab withdrawal or 21, 24, and 30 months from baseline.
Proportion of participants achieving PASI 50
Time frame: 3 months and 6 months
Proportion of participants achieving PASI 75
Time frame: 3 months and 6 months
Proportion of participants achieving PASI 90
Time frame: 3 months and 6 months
Proportion of participants achieving clearance
Time frame: 3 months and 6 months
Quality of life 1 (EuroQoL-5D-5L)
Time frame: 3, 6, 9, 12, 15, 18, 24 and 30 months
Quality of life 2 (Dermatology Life Quality Index - DLQI)
Time frame: 3, 6, 9, 12, 15, 18, 24 and 30 months
Quality of life 3 (Hospital Anxiety and Depression Scale - HADS)
Time frame: 3, 6, 9, 12, 15, 18, 24 and 30 months
Patient Global Assessment
Time frame: 3, 6, 9, 12, 15, 18, 24 and 30 months
Patient Acceptable Symptom State (PASS)
Time frame: 3, 6, 9, 12, 15, 18, 24 and 30 months
Proportion of participants in ixekizumab treatment arm maintaining PASI 50 after ixekizumab withdrawal
Time frame: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm maintaining PASI 75 after ixekizumab withdrawal
Time frame: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm maintaining PASI 90 after ixekizumab withdrawal
Time frame: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm maintaining clearance after ixekizumab withdrawal
Time frame: 9, 12, 18, 24 and 30 months from baseline
Proportion of participants in ixekizumab treatment arm flaring after ixekizumab withdrawal
Time frame: 9, 12, 18, 24 and 30 months from baseline
Histological changes in the skin biopsies of participants in ixekizumab treatment arm who relapsed after ixekizumab withdrawal (or at 18 months if no relapse)
Time frame: Baseline, 6 months, at relapse (or 18 months if no relapse)
Skin genomic profiles in the skin biopsies of participants in ixekizumab treatment arm who relapsed after ixekizumab withdrawal (or at 18 months if no relapse)
Time frame: Baseline, 6 months, at relapse (or 18 months if no relapse)
Peripheral blood immunome profiles of participants in ixekizumab treatment arm who relapsed after ixekizumab withdrawal (or at 18 months if no relapse)
Time frame: Baseline, 6 months, at relapse (or 18 months if no relapse)
Histological changes in the skin biopsies
Time frame: Baseline and 6 months
Skin genomic profiles
Time frame: Baseline and 6 months
Peripheral blood immunome profiles
Time frame: Baseline and 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ying Ying Leung, MD principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ixekizumab, Methotrexate and Cyclosporin A in people with Plaque Psoriasis, run by Singapore General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ying Ying Leung, MD (+65 63265276, katy.leung.y.y@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of ixekizumab treated PsO participants free of relapse after ixekizumab withdrawal (time frame: 12 months from ixekizumab withdrawal or 18 months from baseline.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2022.