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. ledna 2019 aktualizováno: 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.
Přehled studie
Detailní popis
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.
Typ studie
Intervenční
Zápis (Aktuální)
355
Fáze
- Fáze 2
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Part 1: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Ostatní jména:
|
|
Experimentální: Part 1: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Ostatní jména:
|
|
Experimentální: Part 1: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Ostatní jména:
|
|
Experimentální: Part 1: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4
|
SC administration of tildrakizumab at assigned dose
Ostatní jména:
|
|
Komparátor placeba: Part 1: Placebo
Participants receive placebo, SC, at Weeks 0 and 4
|
SC administration of Placebo
|
|
Experimentální: 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
Ostatní jména:
|
|
Experimentální: 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
Ostatní jména:
|
|
Experimentální: 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
Ostatní jména:
|
|
Experimentální: 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
Ostatní jména:
|
|
Žádný zásah: Part 3: Tildrakizumab 5 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
|
|
|
Žádný zásah: Part 3: Tildrakizumab 25 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
|
|
|
Žádný zásah: Part 3: Tildrakizumab 100 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
|
|
|
Žádný zásah: Part 3: Tildrakizumab 200 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
|
|
|
Žádný zásah: Part 3: Placebo Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Percentage of Participants With a PASI 75 Response at Week 12
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- 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.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
25. října 2010
Primární dokončení (Aktuální)
4. listopadu 2011
Dokončení studie (Aktuální)
24. října 2012
Termíny zápisu do studia
První předloženo
7. října 2010
První předloženo, které splnilo kritéria kontroly kvality
20. října 2010
První zveřejněno (Odhad)
21. října 2010
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
5. února 2019
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
18. ledna 2019
Naposledy ověřeno
1. ledna 2019
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- P05495
- 2009-017272-24 (Číslo EudraCT)
- MK-3222-003 (Jiný identifikátor: Merck Research Laboratories)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Studijní data/dokumenty
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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