Why carry out this study?
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Optimal management of psoriasis should include strategies for both the initial, rapid relief of symptoms and the long-term prevention of disease relapse; however, long-term use of potent and super-potent steroids as monotherapy is associated with safety concerns |
We sought to determine if the use of twice-weekly Cal/BD aerosol foam in a novel, proactive treatment regimen for up to 52 weeks could prevent or delay disease relapse in patients with psoriasis vulgaris while minimizing local and systemic adverse events |
The PSO-LONG trial is the first randomized, double-blind, long-term study of its kind to use a topical treatment to maintain psoriasis status as “clear” or “almost clear” for up to 1 year using a patient-friendly approach with just twice-weekly application of a single, fixed-combination product |
What was learned from the study?
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We hypothesized that the time to first relapse in patients with previously cleared skin would be prolonged in those who received proactive therapy with twice-weekly Cal/BD foam as compared with the outcome for patients treated with a conventional, as-needed, reactive approach in which active drug was only administered after relapse occurred |
Superior efficacy of the proactive management with Cal/BD foam was anticipated to be evidenced by a greater number of relapse-free days and fewer relapses compared with controls; a favorable long-term safety profile was also projected |
The outcomes of this novel study will provide valuable insights into the ability of Cal/BD foam to provide a solution for the long-term management of psoriasis in patients with all disease severities and thereby advance the treatment options that can maintain clear skin for patients with this chronic, recurring disease |
Digital Features
Introduction
Background on Psoriasis
Epidemiology
Current Treatment Strategies
Long-Term Clinical Studies of Topical Agents for Treatment of Psoriasis
Calcipotriene Plus Betamethasone Dipropionate (Cal/BD) Foam as a Treatment Option for Psoriasis Vulgaris
Trial Rationale
Methods
Study Design
Screening | Open-label phase, 4 weeks | Maintenance phase | Follow-up phase | |||||||
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SVa | Visit 1b baseline | Visit 2 randomization | V3 to V14 | V15 | UNS/relapse FU visitp | Early withdrawal | FU1q,s | FU2r,s | FU3t | |
Frequency | Every 4 weeks (from V1-baseline to V15) relative to V2 | As needed | ||||||||
Visit window | ± 4 days (from V1-baseline to V15) | No more than 7 days after subject calls in | ± 2 days | ± 4 days | ≤ 7 days after call | |||||
Informed consent for all tests and proceduresc | X | |||||||||
Inc/exclusion criteria | X | X | ||||||||
Baseline demographics, disease characteristics, and medical/psoriasis history and therapy | X | |||||||||
Vital signs (BP, pulse) | X | X | X | X | ||||||
Physical examination | X | X | X | X | ||||||
Concomitant medication and procedures | X | X | X | X | X | X | X | X | X | |
Pregnancy testd | X | X | X | X | X | |||||
Randomization | X | |||||||||
Adverse evente | X | X | X | X | X | X | X | X | X | Xu |
Laboratory biochemistry and urinalysis | X | Xf | Xg | Xg | X | |||||
Laboratory: 25-OH vitamin D | X | |||||||||
Laboratory: ACTH challenge test (assigned sites only)h | X | X | Xi | X | X | X | ||||
Frequency | Every 4 weeks (from V1-baseline to V15) relative to V2 | As needed | ||||||||
Visit window | ± 4 days (from V1-baseline to V15) | No more than 7 days after subject calls in | ± 2 days | ± 4 days | ≤ 7 days after call | |||||
Sampling for biomarkersj | X | Xi | Xk | Xk | ||||||
Subject’s global assessment of disease severity and local safety and tolerability assessment | X | X | X | X | X | X | ||||
Physician’s Global Assessment of disease severity | X | X | X | X | X | X | X | X | ||
Selection of target lesion/location | X | |||||||||
Investigator’s assessment of the severity of the target lesion/location and local safety and tolerability assessment | X | X | X | X | X | X | X | |||
Photographs of the target lesion/locationj,l | X | X | X | X | X | X | ||||
Frequency | Every 4 weeks (from V1-baseline to V15) relative to V2 | As needed | ||||||||
Visit window | ± 4 days (from V1-baseline to V15) | No more than 7 days after subject calls in | ± 2 days | ± 4 days | ≤ 7 days after call | |||||
m-PASI and BSA | X | X | X | X | X | X | X | |||
DLQI and EQ-5D-5L | X | X | X | X | X | X | ||||
WPAI:PSO | X | X | X | X | X | |||||
Psoriasis symptom inventory | Daily during the open-label phase Weekly during the first 28 weeks of the maintenance phase and the last 2 weeks of the maintenance phase (for completers only) | |||||||||
Compliance checkm—eDiary | Daily during the open-label phase Weekly during the maintenance phase (including relapse treatment) | |||||||||
Subject treatment instructions | X | X | X | |||||||
Dispensing of IP | X | X | X | Xn | ||||||
Return of IP | X | X | X | Xo | X | |||||
Drug compliance form | X | X | X | X | X | |||||
End-of-trial form | X | X |
Screening/Washout Phase
Inclusion criteria |
1. Signed and dated informed consent obtained prior to any trial-related activities (including washout period) 2. Age 18 years or above 3. A clinical diagnosis of psoriasis vulgaris for at least 6 months involving the trunk and/or limbs, amenable to treatment with a maximum of 100 g of trial medication per week 4. Psoriasis vulgaris on the trunk and/or limbs (excluding psoriasis on the genitals and skin folds) involving 2–30% BSA 5. PGA of at least “mild” on trunk and limbs at visit 1 6. m-PASI score of at least 2 at visit 1 7. A target lesion/target location of at least 3 cm at its longest axis located on the body (i.e., not on the scalp, face, or intertriginous areas), scoring at least 1 (mild) for each of redness, thickness, and scaliness, and scoring at least 4 in total by the investigator’s assessment of severity of the target lesion/location 8. Women of childbearing potential must have a negative urine pregnancy test at visit 1 9. Women of childbearing potential must agree to use a highly effective method of birth control during the triala 10. Able to communicate with the investigator and understand and comply with the requirements of the trial Additional inclusion criteria for subjects undergoing HPA axis test (assigned sites only) 11. Signed and dated informed consent obtained for having ACTH challenge tests performed 12. An extent of psoriasis vulgaris on trunk and/or limbs of disease severity (PGA) of at least “moderate” affecting between 10% and 30% BSA, excluding psoriatic lesions of the genitals and skin folds, at visit 1 13. At visit 1, a normal HPA axis function, including a serum cortisol concentration > 5 μg/dL before ACTH challenge and > 18 μg/dL at 30 min after ACTH challenge |
Exclusion criteria |
1. Systemic treatment with biologic therapies, whether marketed or not, with a possible effect on psoriasis vulgaris within the following time periods prior to visit 1 Etanercept—within 4 weeks Adalimumab, infliximab—within 8 weeks Ustekinumab—within 16 weeks Secukinumab—within 12 weeks Other products—within 4 weeks or 5 half-lives (whichever is longer) 2. Treatment with any of the following therapies within the following time periods prior to visit 1 Systemic treatment with all other therapies with a possible effect on psoriasis vulgaris—within 4 weeks Systemic treatment with apremilast—within 4 weeks Treatment with any nonmarketed drug substance—within 4 weeks or 5 half-lives (whichever is longer) Psoralen combined with ultraviolet A (PUVA) therapy—within 4 weeks Ultraviolet B (UVB) therapy—within 2 weeks Topical anti-psoriatic treatment on the trunk and/or limbs (except for emollients)—within 2 weeks Topical treatment on the face, scalp, and skin folds with corticosteroids or vitamin D analogues—within 2 weeks 3. Severe and/or extensive scalp psoriasis, which, in the opinion of the investigator, requires treatment with potent or super-potent corticosteroids, which will be prohibited during the trial 4. Preexisting overt atrophy or telangiectasia in treatment areas 5. Planned initiation of, or changes to, concomitant medication that could affect psoriasis vulgaris (e.g., beta blockers, antimalarial drugs, lithium, ACE inhibitors) during the trial 6. Current diagnosis of guttate, erythrodermic, exfoliative, or pustular psoriasis 7. Subjects with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers, and wounds 8. Other inflammatory skin disorders (e.g., seborrheic dermatitis or contact dermatitis) on the treatment area that may confound the evaluation of psoriasis 9. Planned excessive exposure of area(s) to be treated with trial medication to either natural or artificial sunlight (including tanning booths, sun lamps, etc.) during the trial 10. Known or suspected disorders of calcium metabolism associated with hypercalcemia 11. Known or suspected hypersensitivity to component(s) of the investigational products 12. Current participation in any other interventional clinical trial 13. Previously screened in this trial 14. In the opinion of the investigator, the subject is unlikely to comply with the clinical trial protocol (e.g., due to alcoholism, drug addiction, or psychotic state) 15. Women who are pregnant, wishing to become pregnant during the trial, or breastfeeding 16. Subjects in close affiliation with the trial personnel (e.g., immediate family member or subordinate) or a member of the clinical trial personnel; subjects who are an employee of the sponsor or a contract research organization (CRO) involved in the trial 17. Subjects who are institutionalized by court order or by local authority Additional exclusion criteria for subjects undergoing HPA axis test (assigned sites only) 18. A history of allergic asthma, serious allergy, or serious allergic skin rash 19. Known or suspected hypersensitivity to component(s) of Cortrosyn™ (including cosyntropin/tetracosactide) (in the USA) or Synacthen® (including tetracosactide) (in Europe) 20. The use of inhaled corticosteroids in the 4 weeks prior to visit 1 or during the trial 21. Systemic corticosteroid treatment in the 12 weeks prior to visit 1 or during the trial 22. Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to visit 1 or during the trial 23. Systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to visit 1 or during the trial. Topical ketoconazole within 2 weeks prior to visit 1 24. Hypoglycemic sulfonamides within 4 weeks prior to visit 1 or during the trial 25. Antidepressant medications within 4 weeks prior to visit 1 or during the trial. Estrogen therapy (including contraceptives), antidepressant medications, and any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to baseline 26. Not following nocturnal sleep patterns 27. Any of the following conditions, whether known or suspected Depression and endocrine disorders (e.g., Cushing’s disease, Addison’s disease, diabetes mellitus) known to affect cortisol levels or HPA axis integrity Cardiac disorders associated with abnormal QT intervals or rhythm disturbances including clinically significant bradycardia or tachycardia Severe renal insufficiency Severe haptic disorders |
Prohibited medication, including nondrug therapies and procedures | Location | Exclusion period restrictions |
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Systemic treatment with biologic therapies (marketed and nonmarketed), with a possible effect on psoriasis vulgaris | Not applicable | Etanercept: within 4 weeks prior to visit 1 Adalimumab, infliximab: within 8 weeks prior to visit 1 Ustekinumab: within 16 weeks prior to visit 1 Secukinumab: within 12 weeks prior to visit 1 Other products: within 4 weeks or 5 half-lives prior to visit 1 (whichever is longer) and any time during the trial treatment phase |
Systemic treatment with therapies other than biologics, with a possible effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, methotrexate, cyclosporine, and other immunosuppressants) | Not applicable | Within 4 weeks prior to visit 1 and any time during the trial treatment phase |
Systemic treatment with apremilast | Not applicable | Within 4 weeks prior to visit 1 and any time during the trial treatment phase |
Use of nonmarketed or other IPs | Body and scalp | Within 4 weeks or 5 half-lives (whichever is longer) prior to visit 1 and any time during the trial treatment phase |
PUVA | Body and scalp | Within 4 weeks prior to visit 1 and any time during the trial treatment phase |
UVB therapy | Body and scalp | Within 2 weeks prior to visit 1 and any time during the trial treatment phase |
Any topical treatment on the body or scalp, including corticosteroids (except for emollients, nonsteroidal medicated shampoos, and low-potency corticosteroids on sensitive areas) | Body and scalp | Within 2 weeks prior to visit 1 and any time during the trial treatment phase. On areas treated with IP, emollients should not be used on days when IP is being applied |
Initiation of, or changes to, concomitant medication that could affect psoriasis vulgaris (e.g., beta blockers, lithium, antimalaria drugs, ACE inhibitors) | Not applicable | Any time during the trial treatment phase |
Vitamin D supplements > 400 IU/day (note: stable dose of vitamin D supplements ≤ 400 IU/day is permitted) | Not applicable | Any time during the trial treatment phase |
Excessive exposure of treated areas to either natural or artificial sunlight that may affect psoriasis vulgaris (i.e., normal lifestyle outdoor activities are permitted, but deliberate exposure to sunlight or artificial ultraviolet light, as in tanning booths, should be avoided) | Body and scalp | Any time during the trial treatment phase |
Prohibited medications, including nondrug therapies and procedures | Location | Exclusion period restrictions |
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Systemic treatment with corticosteroids | Not applicable | Within 12 weeks prior to visit 1 and any time during the trial treatment phase |
Inhaled corticosteroids | Not applicable | Within 4 weeks prior to visit 1 and any time during the trial treatment phase |
Estrogen therapy (including contraceptives) or any other medication known to affect cortisol levels or HPA axis integrity | Not applicable | Within 4 weeks prior to visit 1 and any time during the trial treatment phase |
Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin), systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole, metronidazole), hypoglycemic sulfonamides, antidepressive medications | Body and scalp | Within 4 weeks prior to visit 1 and any time during the trial treatment phase |
Topical ketoconazole | Body and scalp | Within 2 weeks prior to visit 1 and any time during the trial treatment phase |