A Study to Determine the Optimal Dose of Tildrakizumab (SCH 900222/MK-3222) for the Treatment of Moderate-to-severe Chronic Plaque Psoriasis (P05495) (MK-3222-003)
18 januari 2019 uppdaterad av: Merck Sharp & Dohme LLC
Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Dose-Range Finding Study of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Study P05495)
This is a response-driven study of tildrakuzumab for the treatment of moderate to severe chronic plaque psoriasis.
The primary study hypothesis is that one or more doses of tildrakizumab will be superior to placebo for the treatment of psoriasis.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Each participant will be enrolled in the trial for approximately 72-76 weeks.
Each participant will receive assigned treatment at Weeks 0 and 4 in Part I.
At Week 16, the dosage of treatment the patient is assigned to may be adjusted based on the Psoriasis Area and Severity Index (PASI) 75 response (responder vs non-responder).
Participants will receive study medication once every 12 weeks during Part 2 (Weeks 16 to 52); no participants will receive placebo in Part 2. Part 3 is an observational period and each subject will continue to be monitored on a monthly basis through Week 72.
Subjects will not receive any study medication during Part 3.
Studietyp
Interventionell
Inskrivning (Faktisk)
355
Fas
- Fas 2
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Adult participants (≥18 years of age) with a diagnosis of moderate-to-severe chronic plaque psoriasis (defined by ≥10% body surface area [BSA] involvement, "moderate" or greater score on the Physician's Global Assessment [PGA] scale, and PASI score ≥12 at Baseline)
- Participants must have a diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by interview and confirmation of diagnosis through physical examination by investigator) and be considered candidates for phototherapy or systemic therapy. Participants with psoriatic arthritis may be included in the study
Exclusion Criteria:
- Nonplaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis
- Participants who will require oral or injectable corticosteroids during the trial
- Presence of any infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or serious infection (eg, pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with intravenous antibiotics within 8 weeks prior to Screening
- Participants with evidence of active or untreated latent tuberculosis (TB) according to Screening criteria specified in the protocol. (Prophylactic treatment for latent TB as per local guidelines must be initiated at least 4 weeks prior to treatment with study medication)
- Previous exposure to any agents targeting interleukin-12 (IL-12) and/or Interleukin-23 (IL-23)
- Participants with prior exposure to two or more tumor necrosis factor (TNF) antagonists with discontinuation due to lack of efficacy.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: Part 1: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Experimentell: Part 1: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Experimentell: Part 1: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Experimentell: Part 1: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Placebo-jämförare: Part 1: Placebo
Participants receive placebo, SC, at Weeks 0 and 4
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SC administration of Placebo
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Experimentell: Part 2: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Experimentell: Part 2: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Experimentell: Part 2: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Experimentell: Part 2: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Andra namn:
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Inget ingripande: Part 3: Tildrakizumab 5 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Inget ingripande: Part 3: Tildrakizumab 25 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Inget ingripande: Part 3: Tildrakizumab 100 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Inget ingripande: Part 3: Tildrakizumab 200 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Inget ingripande: Part 3: Placebo Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
Tidsram: Week 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.
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Week 16
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Number of Participants Experiencing Adverse Events
Tidsram: Up to 72 weeks
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An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
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Up to 72 weeks
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Number of Particpants Discontinuing Study Treatment Due to Adverse Events
Tidsram: Up to 52 weeks
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An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Participants may be discontinued from study drug due to adverse events, but remain on the study.
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Up to 52 weeks
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Percentage of Participants With a PASI 75 Response at Week 12
Tidsram: Week 12
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.
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Week 12
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Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at Week 16
Tidsram: Week 16
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The PGA is used to determine the overall severity of a subject's psoriasis lesions at a given time point.
Overall lesions will be graded for induration, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score.
PGA is assessed as: 0= Cleared, except for residual discoloration.
1= Minimal, majority of lesions have individual scores that average .
2 =Mild, majority of lesions have individual scores that average 2. 3= Modreate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5.
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Week 16
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Percentage of Participants With PASI 90 Response at Week 16
Tidsram: Week 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 90 response was defined as >=90 % improvement in PASI score when compared to the baseline score.
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Week 16
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Percentage of Participants With PASI 100 Response at Week 16
Tidsram: Week 16
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The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 100 response was defined as 100 % improvement in PASI score when compared to the baseline score.
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Week 16
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PASI 75 Response Rate by Time
Tidsram: Up to 16 Weeks
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score at Week 2, 4, 6, 8, 12, or 16.
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Up to 16 Weeks
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Mean Change From Baseline in PASI Score at Weeks 12 and 16
Tidsram: Baseline and Weeks 12 and 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
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Baseline and Weeks 12 and 16
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Percentage of Participants With PASI 50 Response at Week 16
Tidsram: Week 16
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The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 50 response was defined as >=50 % improvement in PASI score when compared to the baseline score.
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Week 16
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Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Tidsram: Week 16
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The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life.
Responses range from 0=Not at all to 3=Very much.
The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3).
DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30.
For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
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Week 16
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Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16
Tidsram: Week 16
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The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life.
Responses range from 0=Not at all to 3=Very much.
The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3).
DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30.
For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
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Week 16
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Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16
Tidsram: Week 16
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The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life.
Responses range from 0=Not at all to 3=Very much.
The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3).
DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30.
For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
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Week 16
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Kerbusch T, Li H, Wada R, Jauslin PM, Wenning L. Exposure-response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials. Br J Clin Pharmacol. 2020 Sep;86(9):1795-1806. doi: 10.1111/bcp.14280. Epub 2020 Mar 25.
- Jauslin P, Kulkarni P, Li H, Vatakuti S, Hussain A, Wenning L, Kerbusch T. Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis. Clin Pharmacokinet. 2019 Aug;58(8):1059-1068. doi: 10.1007/s40262-019-00743-7.
- Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. doi: 10.1111/bjd.13932. Epub 2015 Oct 15. Erratum In: Br J Dermatol. 2016 Jun;174(6):1426.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
25 oktober 2010
Primärt slutförande (Faktisk)
4 november 2011
Avslutad studie (Faktisk)
24 oktober 2012
Studieregistreringsdatum
Först inskickad
7 oktober 2010
Först inskickad som uppfyllde QC-kriterierna
20 oktober 2010
Första postat (Uppskatta)
21 oktober 2010
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
5 februari 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
18 januari 2019
Senast verifierad
1 januari 2019
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- P05495
- 2009-017272-24 (EudraCT-nummer)
- MK-3222-003 (Annan identifierare: Merck Research Laboratories)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Studiedata/dokument
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Psoriasis
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ProgenaBiomeRekryteringPsoriasis | Psoriasis Vulgaris | Psoriasis i hårbotten | Psoriasisplack | Psoriasis Universalis | Psoriasis ansikte | Psoriasis Nagel | Psoriasis Diffusa | Psoriasis Punctata | Psoriasis Palmaris | Psoriasis Circinata | Psoriasis Annularis | Psoriasis Genital | Psoriasis GeographicaFörenta staterna
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Clin4allRekryteringPsoriasis i hårbotten | Psoriasis Nagel | Psoriasis Palmaris | Psoriasis Genital | Psoriasis PlantarisFrankrike
-
AmgenAvslutadPsoriasis-Psoriasis | Psoriasis av placktypFörenta staterna
-
Centre of Evidence of the French Society of DermatologyRekryteringPsoriasis | Psoriasis Vulgaris | Psoriasis i hårbotten | Psoriasisplack | Psoriasis Universalis | Psoriasis Palmaris | Psoriatisk erytrodermi | Psoriasisnagel | Psoriasis Guttate | Psoriasis invers | Psoriasis PustulösFrankrike
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UCB Biopharma S.P.R.L.AvslutadMåttlig till svår psoriasis | Generaliserad pustulös psoriasis och erytrodermisk psoriasisJapan
-
Janssen Pharmaceutical K.K.RekryteringGeneraliserad pustulös psoriasis | Erytrodermisk psoriasisJapan
-
Eli Lilly and CompanyAvslutadGeneraliserad pustulös psoriasis | Erytrodermisk psoriasisJapan
-
Innovaderm Research Inc.AvslutadPsoriasis i hårbotten | Pustulös Palmo-plantar Psoriasis | Icke-pustulös Palmo-plantar Psoriasis | Armbågspsoriasis | Psoriasis i underbenetKanada
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TakedaRekryteringGeneraliserad pustulös psoriasis | Erytrodermisk psoriasisJapan
-
PfizerAvslutadPsoriasis Vulgaris | Pustulös psoriasis | Psoriasis Arthropathica | Erytrodermisk psoriasisJapan
Kliniska prövningar på tildrakizumab
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Almirall, S.A.Aktiv, inte rekryterandePlack PsoriasisTyskland, Österrike, Italien, Nederländerna
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University of California, San FranciscoSun Pharmaceutical Industries LimitedAvslutad
-
Almirall, S.A.RekryteringGenital PsoriasisÖsterrike
-
Sun Pharmaceutical Industries LimitedAvslutad
-
Marcelo F. Di Carli, MD, FACCRekrytering
-
Sun Pharmaceutical Industries LimitedAktiv, inte rekryterandeKronisk plackpsoriasis | Måttlig till svår nagelpsoriasisFörenta staterna, Australien
-
Almirall, S.A.Rekrytering
-
Almirall, S.A.AvslutadPlack PsoriasisPolen
-
Medical College of WisconsinAktiv, inte rekryterandeHematologiska maligniteterFörenta staterna
-
Premier Specialists, AustraliaAktiv, inte rekryterandeHudsjukdomar | Vitiligo | Hypopigmentering | Hud- och bindvävssjukdomar | Pigmentationsstörning | BiologiskAustralien