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. januar 2019 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
355
Fase
- Fase 2
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Part 1: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Eksperimentel: Part 1: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Eksperimentel: Part 1: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
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Eksperimentel: Part 1: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Placebo komparator: Part 1: Placebo
Participants receive placebo, SC, at Weeks 0 and 4
|
SC administration of Placebo
|
|
Eksperimentel: Part 2: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Eksperimentel: Part 2: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Eksperimentel: Part 2: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Eksperimentel: Part 2: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks
|
SC administration of tildrakizumab at assigned dose
Andre navne:
|
|
Ingen indgriben: 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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Ingen indgriben: 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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Ingen indgriben: 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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Ingen indgriben: 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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Ingen indgriben: Part 3: Placebo Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
Tidsramme: 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.
|
Week 16
|
|
Number of Participants Experiencing Adverse Events
Tidsramme: Up to 72 weeks
|
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.
|
Up to 72 weeks
|
|
Number of Particpants Discontinuing Study Treatment Due to Adverse Events
Tidsramme: Up to 52 weeks
|
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.
|
Up to 52 weeks
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of Participants With a PASI 75 Response at Week 12
Tidsramme: 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.
|
Week 12
|
|
Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at Week 16
Tidsramme: Week 16
|
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.
|
Week 16
|
|
Percentage of Participants With PASI 90 Response at Week 16
Tidsramme: 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.
|
Week 16
|
|
Percentage of Participants With PASI 100 Response at Week 16
Tidsramme: 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 100 response was defined as 100 % improvement in PASI score when compared to the baseline score.
|
Week 16
|
|
PASI 75 Response Rate by Time
Tidsramme: 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.
|
Up to 16 Weeks
|
|
Mean Change From Baseline in PASI Score at Weeks 12 and 16
Tidsramme: 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).
|
Baseline and Weeks 12 and 16
|
|
Percentage of Participants With PASI 50 Response at Week 16
Tidsramme: 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 50 response was defined as >=50 % improvement in PASI score when compared to the baseline score.
|
Week 16
|
|
Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Tidsramme: Week 16
|
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.
|
Week 16
|
|
Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16
Tidsramme: Week 16
|
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.
|
Week 16
|
|
Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16
Tidsramme: Week 16
|
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.
|
Week 16
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
25. oktober 2010
Primær færdiggørelse (Faktiske)
4. november 2011
Studieafslutning (Faktiske)
24. oktober 2012
Datoer for studieregistrering
Først indsendt
7. oktober 2010
Først indsendt, der opfyldte QC-kriterier
20. oktober 2010
Først opslået (Skøn)
21. oktober 2010
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
5. februar 2019
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
18. januar 2019
Sidst verificeret
1. januar 2019
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- P05495
- 2009-017272-24 (EudraCT nummer)
- MK-3222-003 (Anden identifikator: Merck Research Laboratories)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
JA
IPD-planbeskrivelse
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Studiedata/dokumenter
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .