Trial Information

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)

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.