Chronic Plaque Psoriasis
Conditions
Keywords
Efalizumab,, Chronic plaque psoriasis, moderate to severe, involving, hands, feet
Brief summary
To evaluate the safety and efficacy of Raptiva ® compared with placebo to control chronic moderate to severe plaque psoriasis involving the hands and/or feet scoring Physician's Global Assessment (PGA - H&F) greater-than or equal to 3 in subjects not suitable for other systemic therapies including cyclosporine, methotrexate, and Psoralen-Ultraviolet Light A (PUVA).
Interventions
DRUGEfalizumab - anti CD11a recombinant human monoclonal antibody
Each subject will receive an initial conditioning dose of 0.7 mg/kg/week and then will continue treatment at a dose of 1.0 mg/kg/week. The treatment period will be 24 weeks divided into two phases: 1) double-blind for 12 weeks, and 2) open-label for 12 additional weeks, in which all subjects from the placebo group and those subjects from the Raptiva ® group with ≥ 50% of improvement will be allocated to extended treatment with Raptiva ® for 12 additional weeks while non-responders to Raptiva ® (improvement ≤ 50%) will be followed in an observational manner for 12 additional weeks without treatment.
DRUGPlacebo
Placebo will be administered at Study Day (SD) 1, Week (W) 1, W 4, W 8 and W 12. Each subject will receive an initial conditioning dose of 0.7 mg/kg/week and then will continue treatment at a dose of 1.0 mg/kg/week for 12 weeks (double-blind phase)
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject with chronic (disease history of at least 6 months from diagnosis) moderate to severe plaque psoriasis involving the hands and/or feet (PGA - H&F ratings of 3 or 4) at screening, who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporin, methotrexate and PUVA. Subjects will be outpatients. 2. Stable disease at study entry (i.e. no exacerbation of psoriasis during the screening period). 3. At least 18 years old. 4. For women of childbearing potential, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study. For men, during the participation, it is mandatory to practice birth control, as there are not existing data on the effect of Raptiva ® on spermatogenesis. 5. Discontinuation of any systemic psoriasis treatment at study entry. No washout period is required for these traditional systemic psoriasis agents prior to starting study treatment. 6. Discontinuation of all biological agents at least 3 months prior to first study injection. 7. Discontinuation of any investigational drug or treatment at least 3 months prior to SD 1 or as per washout requirements from previous protocol. 8. Willingness and ability to comply with the protocol requirements for the duration of the study. 9. Written informed consent, given prior to any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw his/her consent at any time without prejudice to future medical care.
Exclusion criteria
1. Hypersensitivity to efalizumab or to any of the excipients 2. Current use of any prohibited therapy (systemic or topical treatments for psoriasis, immunosuppressive drugs, any other experimental drug, etc) 3. Previous or current exposure to Raptiva® 4. History of or ongoing alcohol or drug abuse 5. History of or an ongoing opportunistic infection (e.g. systemic fungal infection, parasites) or any other serious infection. This includes diagnoses that required more than 2 weeks of therapy, such as endocarditis and osteomyelitis, that have been treated in the past 6 months. In addition, if the subject is currently receiving antibiotics, antivirals, or antifungals for an infection or for suppression or prophylaxis for any diagnosis, the subject will be excluded. 6. Seropositivity for hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus (HIV). Subjects will undergo testing during screening, and any subjects who are seropositive for hepatitis B antigen, hepatitis C antibody, or HIV will be excluded. 7. History of active or latent tuberculosis within one year prior to screening (to be determined by assessment according to national and/or local recommendation). 8. Presence or history of malignancy, including lymphoproliferative disorders. 9. Pregnancy or breast-feeding 10. History of hepatic cirrhosis, regardless of cause or severity 11. History of thrombocytopenia, haemolytic anaemia, clinically significant anaemia, a white blood cell count \<4,000 cells/μL or \>14,000 cells/μL, a haematocrit (HCT) \<30% or a haemoglobin (Hgb) level \<11 g/dL, a platelet count \<150,000 cells/μL 12. Hepatic enzyme levels ≥3 times the upper limit of normal or serum creatinine level ≥2 times the upper limit of normal 13. Vaccination with a live or live-attenuated virus or live or live-attenuated bacteria vaccine within the 14 days prior to the first dose of Raptiva® 14. Any medical condition that, in the judgment of the Investigator, would jeopardise the subject's safety following exposure to investigational medicinal product (Raptiva® or placebo equivalent) or would significantly interfere with the Subject's ability to comply with the provisions of this protocol. 15. Other specific forms of psoriasis like guttate, erythrodermic or pustular psoriasis as sole or predominant for of psoriasis. 16. Immunodeficiencies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion Of Participants Achieving A Physician's Global Assessment - Hand & Foot (PGA - H&F) Rating Of Clear, Almost Clear Or Mild At Week 12 | 12 weeks | The proportion of subjects achieving a PGA - H&F rating of clear, almost clear, or mild at Week 12: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet; Mild - Light pink erythema with minimal scaling and with or without pustules on the hands and/or feet |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion Of Participants Achieving A Physician's Global Assessment - Hand & Foot (PGA - H&F) Rating Of Clear, Or Almost Clear At Week 12 | 12 weeks | The proportion of participants achieving a PGA - H&F rating of clear, or almost clear, at Week 12: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet |
| Proportion Of Participants Achieving A Physician's Global Assessment - Hand & Foot (PGA - H&F) Rating Of Clear, Almost Clear Or Mild At Week 24 | 24 weeks | The proportion of participants achieving a PGA - H&F rating of clear, almost clear, or mild at Week 24: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet; Mild - Light pink erythema with minimal scaling and with or without pustules on the hands and/or feet |
| Proportion of Participants From the Initial Placebo Group Achieving a PGA - H&F of Rating of Clear, Almost Clear, or Mild From Week 12 to Week 24. | 24 weeks | The proportion of participants achieving a PGA - H&F rating of clear, or almost clear, at Week 24: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet; Mild - Light pink erythema with minimal scaling and with or without pustules on the hands and/or feet |
| Proportion Of Participants Achieving A Physician's Global Assessment (PGA) Rating of Good, Excellent, Or Cleared At Week 12 | 12 weeks | The proportion of participants achieving a PGA rating of good, excellent, or cleared at Week 12. Cleared = 100% improvement; Excellent = 75-99% improvement; Good = 50-74% improvement |
| Proportion Of Participants Achieving A Physician's Global Assessment (PGA) Rating of Excellent, Or Cleared At Week 12 | 12 weeks | The proportion of participants achieving a PGA rating of excellent, or cleared at Week 12. Cleared = 100% improvement; Excellent = 75-99% improvement |
Countries
Austria
Participant flow
Recruitment details
First subject's first visit: 08 April 2008, last subject's last visit: 15 June 2009. Seventy six subjects entered the study, 46 completed the double-blind period and 31 of these then entered the open-label period. The remaining 15 entered an observational follow-up.
Pre-assignment details
During the screening period, approximately 200 subjects were to be screened for trial eligibility within 14 days before Day 1. A total of 100 subjects had been screened at the time the trial was terminated, of whom 76 subjects were enrolled in the trial.
Participants by arm
| Arm | Count |
|---|---|
| Efalizumab Each subject will receive an initial conditioning dose of 0.7 mg/kg/week and then will continue treatment at a dose of 1.0 mg/kg/week. The treatment period will be 24 weeks divided into two phases: 1) double-blind for 12 weeks, and 2) open-label for 12 additional weeks, in which all subjects from the placebo group and those subjects from the Raptiva ® group with ≥ 50% of improvement will be allocated to extended treatment with Raptiva ® for 12 additional weeks while non-responders to Raptiva ® (improvement ≤ 50%) will be followed in an observational manner for 12 additional weeks without treatment. | 51 |
| Placebo Placebo will be administered at Study Day (SD) 1, Week (W) 1, W 4, W 8 and W 12. Each subject will receive an initial conditioning dose of 0.7 mg/kg/week and then will continue treatment at a dose of 1.0 mg/kg/week for 12 weeks (double-blind phase) | 25 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period | Adverse Event | 1 | 2 |
| Double-blind Period | Lack of Efficacy | 1 | 1 |
| Double-blind Period | Other | 16 | 8 |
| Double-blind Period | Protocol Violation | 1 | 0 |
| Open-label Period | Adverse Event | 1 | 0 |
| Open-label Period | Other | 9 | 5 |
Baseline characteristics
| Characteristic | Total | Placebo | Efalizumab |
|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 13.1 | 51.7 years STANDARD_DEVIATION 12.9 | 49.0 years STANDARD_DEVIATION 13.3 |
| Age, Customized 18-40 years | 20 participants | 4 participants | 16 participants |
| Age, Customized 41-64 years | 46 participants | 17 participants | 29 participants |
| Age, Customized >64 years | 10 participants | 4 participants | 6 participants |
| Region of Enrollment Austria | 11 participants | 4 participants | 7 participants |
| Region of Enrollment Belgium | 4 participants | 0 participants | 4 participants |
| Region of Enrollment France | 13 participants | 5 participants | 8 participants |
| Region of Enrollment Germany | 18 participants | 4 participants | 14 participants |
| Region of Enrollment Italy | 4 participants | 2 participants | 2 participants |
| Region of Enrollment Netherlands | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Spain | 11 participants | 4 participants | 7 participants |
| Region of Enrollment Turkey | 13 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 31 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 45 Participants | 15 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 51 | 13 / 25 | 8 / 17 | 7 / 14 |
| serious Total, serious adverse events | 1 / 51 | 1 / 25 | 0 / 17 | 2 / 14 |
Outcome results
Primary
Proportion Of Participants Achieving A Physician's Global Assessment - Hand & Foot (PGA - H&F) Rating Of Clear, Almost Clear Or Mild At Week 12
The proportion of subjects achieving a PGA - H&F rating of clear, almost clear, or mild at Week 12: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet; Mild - Light pink erythema with minimal scaling and with or without pustules on the hands and/or feet
Time frame: 12 weeks
Population: Due to the termination of the trial, analysis of efficacy-related endpoints was not performed
Secondary
Proportion Of Participants Achieving A Physician's Global Assessment - Hand & Foot (PGA - H&F) Rating Of Clear, Almost Clear Or Mild At Week 24
The proportion of participants achieving a PGA - H&F rating of clear, almost clear, or mild at Week 24: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet; Mild - Light pink erythema with minimal scaling and with or without pustules on the hands and/or feet
Time frame: 24 weeks
Population: Due to the termination of the trial, analysis of efficacy-related endpoints was not performed
Secondary
Proportion Of Participants Achieving A Physician's Global Assessment - Hand & Foot (PGA - H&F) Rating Of Clear, Or Almost Clear At Week 12
The proportion of participants achieving a PGA - H&F rating of clear, or almost clear, at Week 12: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet
Time frame: 12 weeks
Population: Due to the termination of the trial, analysis of efficacy-related endpoints was not performed
Secondary
Proportion Of Participants Achieving A Physician's Global Assessment (PGA) Rating of Excellent, Or Cleared At Week 12
The proportion of participants achieving a PGA rating of excellent, or cleared at Week 12. Cleared = 100% improvement; Excellent = 75-99% improvement
Time frame: 12 weeks
Population: Due to the termination of the trial, analysis of efficacy-related endpoints was not performed
Secondary
Proportion Of Participants Achieving A Physician's Global Assessment (PGA) Rating of Good, Excellent, Or Cleared At Week 12
The proportion of participants achieving a PGA rating of good, excellent, or cleared at Week 12. Cleared = 100% improvement; Excellent = 75-99% improvement; Good = 50-74% improvement
Time frame: 12 weeks
Population: Due to the termination of the trial, analysis of efficacy-related endpoints was not performed
Secondary
Proportion of Participants From the Initial Placebo Group Achieving a PGA - H&F of Rating of Clear, Almost Clear, or Mild From Week 12 to Week 24.
The proportion of participants achieving a PGA - H&F rating of clear, or almost clear, at Week 24: Clear - No signs of plaque psoriasis on the hands and/or feet; Almost Clear - Just perceptible erythema and just perceptible scaling on the hands and/or feet; Mild - Light pink erythema with minimal scaling and with or without pustules on the hands and/or feet
Time frame: 24 weeks
Population: Due to the termination of the trial, analysis of efficacy-related endpoints was not performed