Psoriasis
Conditions
Keywords
Psoriasis, Infliximab, Remicade
Brief summary
The purpose of this study is to determine the superiority and efficacy of infliximab induction therapy in chinese participants with moderate to severe plaque-type psoriasis (scaly skin rash) compared with placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial).
Detailed description
This is a double-blind (neither physician nor participant knows the treatment that the participant receives), multicenter (when more than one hospital or medical school team work on a medical research study) and placebo-controlled study of infliximab in participants with moderate to severe plaque-type psoriasis. All the eligible participants will be randomly assigned to infliximab and placebo groups. The infliximab group will receive 5 milligram per kilogram (mg/kg) infliximab infusions (a fluid or a medicine delivered into a vein by way of a needle) intravenously (into a vein) at Week 0, 2 and 6 in the induction treatment phase followed by maintenance regimen of the intervention every 8 weeks up to 26 weeks. Placebo infusions will also be given at Week 10, 12 and 16. The placebo group will receive placebo infusion at Week 0, 2, 6, 14 and 22. At Week 10, participants in placebo group will then receive infliximab induction therapy. Efficacy of the participants will primarily be evaluated by percentage of participants who achieve a Psoriasis Area and Severity Index 75 (PASI) response at Week 10. Participants' safety will be monitored throughout the study.
Interventions
DRUGPlacebo
Placebo matched to infliximab given at Weeks 10, 12 and 16 in Infliximab arm and at Weeks 0, 2 and 6 in Placebo arm
DRUGInfliximab
5 mg/kg infusion given intravenously at Week 0,2,6 (induction treatment phase) and at Week 14 and 22 in maintenance phase in infliximab arm and at Week 12 and 16 in Placebo arm.
Sponsors
Xian-Janssen Pharmaceutical Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The body weight should be less than or equal to 80 kilogram * Participants who had a diagnosis of plaque-type psoriasis (scaly skin rash) greater than or equal to 6 months before Screening (participants with concurrent psoriatic arthritis \[joint pain\] may be enrolled) * Participants who had plaque-type psoriasis covering greater than or equal to 10 percent of total body surface area, Psoriasis Area Severity Index (PASI) score greater than or equal to 12 at Screening and at the Baseline * Participants who are candidates for systemic treatment of psoriasis * Females of childbearing potential and all men must be using adequate birth control measures and agree to use these measures and should not become pregnant (carrying an unborn baby) or plan to become pregnant up to 6 months after receiving last infusion of study drug
Exclusion criteria
* Participants who have nonplaque forms of psoriasis ( for example, erythrodermic, guttate, or pustular), or have current drug-induced psoriasis (for example, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium) * Participants who are pregnant, nursing or planning to become pregnant within one year while enrolled in the study * Participants who had previous treatment with infliximab * Participants who have received agents targeted at reducing tumour necrosis factor or any biologic treatment within the previous 3 months * Participants who have used any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Greater Than Equal to 75 Percent Response in Psoriasis Area and Severity Index (PASI) | Week 10 | The PASI score is based on the assessment of the erythema (e), induration (I), scaling (S), and the body is divided into 4 regions head, trunk, upper extremities, lower extremities. The assessment was done on 4-point scale (where, 0 = none, 1 = slight, 2 = moderate, 3 = severe, and 4 = very severe). The total possible score ranges from 0 (no disease) to 72 (maximal disease). Participants with no less than 75 percent relative Baseline improvement in the PASI scores are considered to be PASI 75 responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 10 | Baseline and Week 10 | The DLQI is a dermatology-specific quality of life (QOL) instrument designed to assess impact of disease on a participants QOL. It is a 10-item questionnaire that, in addition to evaluating overall, QOL can be used to assess 6 different aspects: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships and treatment. Questions scored on a 4-point Likert scale: 0 (not relevant), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual items (0-3) were added to yield a total score (0-30); higher score = greater impairment of participants QOL. |
| Percentage of Participants With Static Physician Global Assessment (PGA) Score Less Than Equal to 1 at Week 10 | Week 10 | The Static physician global assessment (PGA) determines psoriasis lesions overall at given time point. Overall lesions graded for I (0= no evidence of plaque elevation to 5= severe plaque elevation), E (0 = no evidence of E, hyperpigmentation may be present to 5=dusky to deep red coloration), S (0 = no evidence of S to 5 = severe; very thick tenacious scale predominates). Sum of 3 scales divided by 3 gives final PGA score. Range for final score is 0 = cleared, except for residual discoloration, 1 = minimal, 2 = mild, 3=moderate, 4= marked and 5= severe; Scores should be rounded to the nearest whole number. If total ≤1.49, score = 1; if total≥ 1.50, score = 2. Percentage of participants with static PGA score \<= 1 at week 10 were reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 26 | Baseline and Week 26 | The DLQI is a dermatology-specific QOL instrument designed to assess impact of disease on a participants QOL. It is a 10-item questionnaire that, in addition to evaluating overall, QOL can be used to assess 6 different aspects: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships and treatment. Questions scored on a 4-point Likert scale: 0 (not relevant), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual items (0-3) were added to yield a total score (0-30); higher score = greater impairment of participants QOL. |
| Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | Baseline up to end of study (Week 26) | The AE is defined as any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); significant disability; congenital (occurred before birth, due to parent's genetic input) anomaly. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infliximab 5 milligram per kilogram (mg/kg) infusion (a fluid or a medicine delivered into a vein by way of a needle) of infliximab administered intravenously (into a vein) at Week 0, 2 and 6 during induction treatment phase followed by maintenance regimen of 5 mg/kg infliximab at Week 14 and 22. Placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial infusion), matched to infliximab was given at Week 10, 12 and 16. Total duration of treatment was 26 weeks. | 84 |
| Placebo Placebo infusion, matched to infliximab was given intravenously at Week 0, 2 and 6. At Week 10, 12 and 16, participants received 5 mg/kg infliximab intravenously. Placebo infusion was again given at Week 14 and 22. Total duration of treatment was 26 weeks. | 45 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal of informed consent | 0 | 1 |
Baseline characteristics
| Characteristic | Infliximab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 12.3 | 40.1 years STANDARD_DEVIATION 11.1 | 39.7 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 24 Participants | 10 Participants | 34 Participants |
| Sex: Female, Male Male | 60 Participants | 35 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 84 | 28 / 45 |
| serious Total, serious adverse events | 4 / 84 | 1 / 45 |
Outcome results
Primary
Percentage of Participants Who Achieved a Greater Than Equal to 75 Percent Response in Psoriasis Area and Severity Index (PASI)
The PASI score is based on the assessment of the erythema (e), induration (I), scaling (S), and the body is divided into 4 regions head, trunk, upper extremities, lower extremities. The assessment was done on 4-point scale (where, 0 = none, 1 = slight, 2 = moderate, 3 = severe, and 4 = very severe). The total possible score ranges from 0 (no disease) to 72 (maximal disease). Participants with no less than 75 percent relative Baseline improvement in the PASI scores are considered to be PASI 75 responders.
Time frame: Week 10
Population: Intent to treat (ITT) population included all participants randomly assigned to Infliximab or placebo group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab | Percentage of Participants Who Achieved a Greater Than Equal to 75 Percent Response in Psoriasis Area and Severity Index (PASI) | 81 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a Greater Than Equal to 75 Percent Response in Psoriasis Area and Severity Index (PASI) | 2.2 percentage of participants |
p-value: <0.001Fisher Exact
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 10
The DLQI is a dermatology-specific quality of life (QOL) instrument designed to assess impact of disease on a participants QOL. It is a 10-item questionnaire that, in addition to evaluating overall, QOL can be used to assess 6 different aspects: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships and treatment. Questions scored on a 4-point Likert scale: 0 (not relevant), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual items (0-3) were added to yield a total score (0-30); higher score = greater impairment of participants QOL.
Time frame: Baseline and Week 10
Population: ITT population included all participants randomly assigned to Infliximab or placebo group. Here 'n' included those participants who were evaluable for this measure at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infliximab | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 10 | Baseline (n= 84,45) | 14.4 units on a scale | Standard Deviation 6.2 |
| Infliximab | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 10 | Change at Week 10 (n= 82,44) | -8.0 units on a scale | Standard Deviation 7.1 |
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 10 | Baseline (n= 84,45) | 14.4 units on a scale | Standard Deviation 6.3 |
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 10 | Change at Week 10 (n= 82,44) | -1.5 units on a scale | Standard Deviation 5.1 |
Comparison: Change at Week 10: p-value was calculated by Non parametric ANOVA by van der Waerden method.p-value: <0.001Non parametric ANOVA by van der Waerden
Secondary
Percentage of Participants With Static Physician Global Assessment (PGA) Score Less Than Equal to 1 at Week 10
The Static physician global assessment (PGA) determines psoriasis lesions overall at given time point. Overall lesions graded for I (0= no evidence of plaque elevation to 5= severe plaque elevation), E (0 = no evidence of E, hyperpigmentation may be present to 5=dusky to deep red coloration), S (0 = no evidence of S to 5 = severe; very thick tenacious scale predominates). Sum of 3 scales divided by 3 gives final PGA score. Range for final score is 0 = cleared, except for residual discoloration, 1 = minimal, 2 = mild, 3=moderate, 4= marked and 5= severe; Scores should be rounded to the nearest whole number. If total ≤1.49, score = 1; if total≥ 1.50, score = 2. Percentage of participants with static PGA score \<= 1 at week 10 were reported.
Time frame: Week 10
Population: ITT population included all participants randomly assigned to Infliximab or placebo group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab | Percentage of Participants With Static Physician Global Assessment (PGA) Score Less Than Equal to 1 at Week 10 | 88.1 percentage of participants |
| Placebo | Percentage of Participants With Static Physician Global Assessment (PGA) Score Less Than Equal to 1 at Week 10 | 6.7 percentage of participants |
p-value: <0.001Fisher Exact
Other Pre-specified
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 26
The DLQI is a dermatology-specific QOL instrument designed to assess impact of disease on a participants QOL. It is a 10-item questionnaire that, in addition to evaluating overall, QOL can be used to assess 6 different aspects: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships and treatment. Questions scored on a 4-point Likert scale: 0 (not relevant), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual items (0-3) were added to yield a total score (0-30); higher score = greater impairment of participants QOL.
Time frame: Baseline and Week 26
Population: ITT population included all participants randomly assigned to Infliximab or placebo group. 'n' included those participants who were evaluable for this measure at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infliximab | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 26 | Baseline (n= 84,45) | 14.4 units on a scale | Standard Deviation 6.2 |
| Infliximab | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 26 | Change at Week 26 (n= 80,42) | -10.3 units on a scale | Standard Deviation 7.8 |
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 26 | Baseline (n= 84,45) | 14.4 units on a scale | Standard Deviation 6.3 |
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 26 | Change at Week 26 (n= 80,42) | -9.2 units on a scale | Standard Deviation 6.6 |
Comparison: Change at Week 26: p-value was calculated by Non parametric ANOVA by van der Waerden method.p-value: <0.001Non parametric ANOVA by van der Waerden
Other Pre-specified
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
The AE is defined as any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); significant disability; congenital (occurred before birth, due to parent's genetic input) anomaly.
Time frame: Baseline up to end of study (Week 26)
Population: Safety Population included all participants randomly assigned to infliximab or placebo group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infliximab | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs | 59 participants |
| Infliximab | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | SAE | 4 participants |
| Placebo | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs | 29 participants |
| Placebo | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | SAE | 1 participants |