A Safety and Efficacy Study of Ustekinumab in Patients With Plaque Psoriasis Who Have Had an Inadequate Response to Methotrexate
Information source: Janssen-Cilag International NV
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Psoriasis
Intervention: Ustekinumab (Drug); Methotrexate (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Janssen-Cilag International NV Official(s) and/or principal investigator(s): Janssen-Cilag International NV Clinical Trial, Study Director, Affiliation: Janssen-Cilag International NV
Summary
This purpose of this study is to assess the safety of ustekinumab in psoriasis patients who
receive ustekinumab following an inadequate response to methotrexate therapy. The study
will provide information for doctors on how to manage the transfer from methotrexate to the
biologic agent ustekinumab. The study is designed to compare two methods of transferring
patients from methotrexate to ustekinumab. The two methods being compared are
discontinuation of methotrexate with immediate initiation of ustekinumab versus initiation
of ustekinumab with overlap and gradual dose reduction of methotrexate over 4 weeks.
Clinical Details
Official title: An Exploratory Trial to Assess Naturalistic Safety and Efficacy Outcomes in Patients With Moderate to Severe Plaque Psoriasis Transitiioned to Ustekinumab From Previous Methotrexate Therapy (TRANSIT)
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Number of Patients Experiencing One or More Adverse Events Occurring From Week 0 Through Week 12
Secondary outcome: Rate of Adverse Events (AEs), Serious AEs (SAEs) and Deaths During the Study PeriodRate of Severe AEs, Reasonably Related AEs, and AEs Leading to Discontination During the Study Period Rate of Infections, Severe Infections and Infections Requiring Oral or Parenteral Antimicrobial Treatment During the Study Period Rate of Malignancies and Other Events of Clinical Interest (Tuberculosis, Serious Cardiovascular Events, Anaphylactic/Serum Sickness Reaction) Change in Mean Psoriasis Area-and-severity Index (PASI) Score Compared to Baseline Proportion of Patients Achieving PASI 50 Response Proportion of Patients Achieving PASI 75 Response Proportion of Patients Achieving PASI 90 Response
Detailed description:
Only limited data exist to guide physicians on transitioning patients onto biologic agents
once conventional systemic agents have been found to be inadequate. Most Phase III
regulatory studies for biologics, including ustekinumab, required washout periods of between
one and three months between previous therapies and the start of study agent. Although
advantageous from a methodological perspective, this approach does not appear to mirror
real-world clinical practice, in which clinicians and patients are unwilling to go without
treatment for extended periods. As a result, physicians appear to employ several arbitrary
strategies when transitioning their patients. Two commonly used approaches are: Initiation
of biologic therapy with immediate cessation of previous conventional systemic therapy or
Initiation of biologic therapy with overlap and gradual reduction of previous conventional
systemic therapy. Some physicians opt for the first strategy to minimise the risk of
drug-drug interactions. Others opt for the second strategy to minimise the risk of
symptomatic worsening between cessation of previous treatment and the onset of action of
biologic agents. This study aims to compare safety, efficacy and quality of life outcomes
associated with these two strategies, with follow-up for 52 weeks. The primary objective of
this exploratory trial is to evaluate the comparative safety through week 12 of two
treatment transition strategies in patients with inadequate response to methotrexate:
discontinuation of methotrexate with immediate initiation of ustekinumab versus initiation
of ustekinumab with overlap and gradual dose reduction of methotrexate over 4 weeks.
Secondary objectives of the study include evaluating the safety, efficacy, and quality of
life through Week 52. The focus of the trial is on estimation rather than on hypothesis
testing and, therefore, no formal hypothesis testing is planned. The primary endpoint is
the proportion of patients experiencing one or more treatment-emergent adverse events (AEs)
through Week 12 within each treatment transition arm. All proportions will be accompanied by
an estimated 95% confidence interval. This is a phase IIIB/IV multicentre, open label,
two-arm, randomised study, lasting 56 weeks (including a screening period). The primary
endpoint is assessed after 12 weeks of treatment (Week 12). All treated patients will be
followed for safety and efficacy through Week 52. Patients will be stratified according to
their body weight to ensure a similar distribution of patients >100 kg between the two
treatment arms. Approximately 4 weeks prior to study start, all patients who provide consent
for participation will be screened according to the requirements of the inclusion and
exclusion criteria. Patients who meet all of the inclusion criteria and none of the
exclusion criteria will enter the study. During the Screening Phase, patients will continue
their current treatment schedule and dose for methotrexate, with folic acid if prescribed.
At Week 0, prior to the first dose of ustekinumab, patients will be randomised 1: 1 to one of
the two treatment arms described below. Patients will be stratified according to their
baseline body weight (=<100 kg or >100 kg) to ensure a similar distribution of patients >100
kg between the two treatment arms. Patients eligible for the study will be men and women
aged 18 years or older with moderate to severe plaque psoriasis who have a Psoriasis Area
and Severity Index (PASI) >=10, who have failed or are intolerant to methotrexate therapy.
Patients entering the study must be receiving methotrexate at a dose of 10-25 mg/week, and
should have been receiving methotrexate for at least 8 weeks prior to screening.
Approximately 576 patients will be included in the study from approximately 100 sites in 20
countries. In both treatment arms, Patients weighing ≤ 100 kg will receive ustekinumab 45 mg
at Weeks 0, 4 and 16. Patients who achieve a PASI 75 response at Week 28 and 40 will
continue receiving ustekinumab 45 mg at Week 28 and 40. Patients who fail to achieve PASI 75
response at Week 28 will receive ustekinumab 90 mg at Week 28 and 40. Patients who achieve a
PASI 75 response at Week 28, but fail to achieve PASI 75 response at Week 40 will receive
ustekinumab 90 mg at Week 40. Patients > 100 kg will receive ustekinumab 90 mg at Weeks 0,
4, 16, 28 and 40, regardless of achievement of PASI 75 response. Consideration will be given
to discontinuing treatment in these patients if they show no response at Week 28. At Week 0,
all eligible patients will be randomised to one of the following treatment regimens. The
methotrexate dose reduction regime will depend on the dose of methotrexate at screening. All
patients will stop methotrexate regardless of the final dose after 4 overlapping weeks
(Weeks 0, 1, 2 and 3). The last dose of methotrexate will be given within the 7 day period
before the second dose of ustekinumab. Safety evaluations will include physical examination,
body weight and waist circumference, pregnancy testing, vital signs, clinical laboratory
testing with full blood analysis and biochemistry, skin assessment for suspicious malignant
lesions, Tuberculosis (TB) assessment, adverse events review and collection. Efficacy
evaluations, including Psoriasis Area Severity Index (PASI), Nail Psoriasis Severity Index
(NAPSI) and Physician's Global Assessment (PGA), will be carried out. Evaluations to assess
changes in quality of life, including the Dermatology Life Quality Index (DLQI), Hospital
Anxiety Depression Score (HADS), EuroQol-5 dimensional questionnaire (EQ-5D) and Patient
Benefit Index (PBI), will be carried out.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients should have diagnosis of plaque-type psoriasis for at least 6 months prior
to first administration of study agent (patients with concurrent psoriatic arthritis
may be enrolled)
- Moderate-to-severe psoriasis scored as PASI >= 10 at screening and at the time of
first administration of ustekinumab
- Should currently receive (and have been receiving for at least 8 weeks directly prior
to screening) systemic therapy with methotrexate at a dose of at least 10 mg/week but
not exceeding 25 mg/week, with an inadequate response to this treatment (due to
either efficacy or tolerability) and, in the judgment of the treating physician and
patient, a treatment change is needed
- Women should take adequate birth control measures throughout the study and must agree
to continue to use such birth control measures and not to become pregnant or plan to
become pregnant for at least 15 weeks after the last dose of ustekinumab and for at
least 6 months after the last dose of methotrexate
- Men must be using adequate birth control measures whilst receiving methotrexate and
for 6 months after the last dose of methotrexate
Exclusion Criteria:
- Patients should not have non-plaque forms of psoriasis (eg, erythrodermic, guttate,
or pustular)
- Should currently (and within 12 months) not receive ciclosporin, fumarates, PUVA,
etanercept, efalizumab, infliximab, adalimumab or alefacept or other biologic or
systemic therapy (and other therapy as indicated in the protocol)
- Women who are pregnant, breastfeeding, or planning pregnancy (both men and women)
while enrolled in the study
- Have previously failed treatment with any therapeutic agent directly targeted at
reducing IL-12 or IL-23, including, but not limited to, ustekinumab and ABT-874
- Active or latent Tuberculosis or other chronic or recurrent infectious disease
- Known history of lymphoproliferative disease
- Known malignancy or history of malignancy
Locations and Contacts
Wien, Austria
Brussels, Belgium
Gent, Belgium
Liège, Belgium
Pleven, Bulgaria
Sofia, Bulgaria
Aarhus, Denmark
Roskilde N/A, Denmark
Tampere, Finland
Turku, Finland
Chambray-Lès-Tours, France
Creil, France
Jarez, France
Lille Cedex, France
Marseille, France
Montpellier N/A, France
Nantes Cedex 01 N/A, France
Nantes Cedex 1, France
Nice Cedex 3, France
Paris, France
Pessac, France
Pierre Benite, France
Poitiers, France
Rouen, France
Toulouse, France
Berlin, Germany
Dresden, Germany
Erlangen, Germany
Essen, Germany
Frankfurt, Germany
Gottingen, Germany
Hamburg, Germany
Kiel, Germany
Landau, Germany
Leipzig, Germany
Mahlow, Germany
Marburg, Germany
Munster, Germany
München, Germany
Tÿbingen, Germany
Witten, Germany
Athens, Greece
Thessaloniki, Greece
Debrecen, Hungary
Szeged, Hungary
Petah-Tikva, Israel
Tel-Aviv, Israel
Kaunas, Lithuania
Vilnius, Lithuania
Nijmegen, Netherlands
Rotterdam, Netherlands
Oslo N/A, Norway
Stavanger, Norway
Poznan, Poland
Wrocław, Poland
Łódź, Poland
Lisboa, Portugal
Porto, Portugal
Bratislava, Slovakia
Alicante, Spain
Badalona, Spain
Barcelona, Spain
Cordoba, Spain
La Coruÿa N/A, Spain
Madrid, Spain
Göteborg, Sweden
Malmö, Sweden
Solna, Sweden
Uppsala, Sweden
Aberdeen, United Kingdom
Cardiff, United Kingdom
Craigavon, United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Nottingham, United Kingdom
Salford, United Kingdom
Additional Information
Starting date: October 2009
Last updated: November 13, 2014
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