Candidates for Systemic Therapy for Psoriasis, Psoriasis
Conditions
Brief summary
An open-label, multi-center study to establish psoriasis control of moderate to severe plaque psoriasis with Raptiva therapy administered subcutaneously for 24 weeks.
Interventions
DRUGEfalizumab
Subjects will receive a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* A) In the opinion of the investigator, candidate for systemic therapy for psoriasis could include: * Patients with moderate to severe plaque psoriasis defined by Psoriasis Area and Severity Index (PASI) less than (\>) 10 and body surface area (BSA) greater than (\>) 10 * Patients with the following may also be deemed to require systemic therapy in the judgement of the physician: * Severe psychosocial disability (in the judgement of the physician), or * Nail psoriasis, or * Scalp psoriasis, or * Palmar plantar psoriasis etc OR * B) Subjects who have completed the CLEAR study investigational medicinal product (IMP) 24011 (NCT00256139) and who wish to continue Raptiva (efalizumab) therapy. * Body weight of 120 kg * 18 to 75 years old * For women of childbearing potential and for men whose partner can become pregnant, 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 up to 3 months after the last dose of Raptiva * Willingness to hold sun exposure reasonably constant and to avoid use of tanning booths or other ultraviolet (UV) light sources during the study * Agreement to participate in the study * Signed informed consent * Discontinuation of any systemic psoriasis treatment prior to commencement of the study drug. No washout period is required for these agents prior to starting study and receiving first dose of study drug (Raptiva) * Discontinuation of all biologic agents (other than Raptiva) 3 months prior to receiving first dose of study drug (Raptiva) * Discontinuation of Psoralen-ultraviolet light A (PUVA), Ultraviolet light B (UVB) treatment 28 days prior to commencement of receiving first dose of study drug. * Discontinuation of any investigational drug or treatment 3 months prior to study Day 0 or as per washout requirements from previous protocol * No vaccinations (e.g., tetanus, booster, influenza vaccine) at least 14 days prior to first dose of study drug * Treatment regimens of b-blockers, Angiotensin-converting enzyme (ACE) inhibitors, antimalarial drugs, quinidine, interferon, or lithium stable for at least 28 days prior to first dose of study drug
Exclusion criteria
* Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis * Active rebound of psoriasis during or following discontinuation of the previous Raptiva treatment( PASI \>125% from baseline and/or new predominant morphology of psoriasis) when reason was adverse event or lack of efficacy of Raptiva. If it was due to another non drug reason (vaccination, or infection) then the patient can be included in this study. * History of severe allergic or anaphylactic reactions to humanised monoclonal antibodies * History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection * History of opportunistic infections (e.g., systemic fungal infections, parasites) * Seropositivity for human immunodeficiency virus (HIV). Patients will undergo mandatory testing at screening. Patients who are positive for HIV will be excluded. * Pregnancy or lactation * White blood cell (WBC) count \<4000 per Liter (L) or \>14,000/L * Patient with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count \< 00,000 cells/L * Seropositivity for hepatitis B or C virus Patients will undergo testing at screening. Patients who are positive for hepatitis B antigen or hepatitis C antibody will be excluded. * Hepatic enzymes \>3 times the upper limit of normal * History of active tuberculosis (TB) or currently undergoing treatment for TB within one year prior to study Day 0. Chest X-ray (within 3 months prior to Study Day 0) is required for high-risk patients. Patients with a positive chest X-ray will be excluded. * Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Patients with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled. * Diagnosis of hepatic cirrhosis, regardless of cause or severity * Serum creatinine \>2 times the upper limit of normal * Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year * History of substance abuse within the last 5 years * Any medical condition that, in the judgment of the investigator, would jeopardize the patient's safety following exposure to study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Physician's Global Assessment (PGA) Ratings of Excellent or Cleared at Week 24 | Week 24 | The PGA rating was used to assess the global response of all psoriatic lesions by comparing subject's present condition to baseline photographs or body diagrams. The response was classified as Cleared: 100% improvement of all clinical signs and symptoms compared to baseline; Excellent: 75% to 99% improvement of all signs and symptoms compared to baseline; Good: 50% to 74% improvement of signs and symptoms compared to baseline; Fair: 25% to 49% improvement of signs and symptoms compared to baseline; Slight: 1% to 24% improvement of signs and symptoms compared to baseline; Unchanged: Clinical signs and symptoms unchanged from baseline and Worse: Clinical signs and symptoms deteriorated from baseline. |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Efalizumab Subjects received a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks. | 189 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 30 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 11 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 7 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Efalizumab |
|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 12.8 |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 161 / 189 |
| serious Total, serious adverse events | 21 / 189 |
Outcome results
Primary
Percentage of Subjects With Physician's Global Assessment (PGA) Ratings of Excellent or Cleared at Week 24
The PGA rating was used to assess the global response of all psoriatic lesions by comparing subject's present condition to baseline photographs or body diagrams. The response was classified as Cleared: 100% improvement of all clinical signs and symptoms compared to baseline; Excellent: 75% to 99% improvement of all signs and symptoms compared to baseline; Good: 50% to 74% improvement of signs and symptoms compared to baseline; Fair: 25% to 49% improvement of signs and symptoms compared to baseline; Slight: 1% to 24% improvement of signs and symptoms compared to baseline; Unchanged: Clinical signs and symptoms unchanged from baseline and Worse: Clinical signs and symptoms deteriorated from baseline.
Time frame: Week 24
Population: The Intent to Treat (ITT) population consisted of all subjects who received at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efalizumab | Percentage of Subjects With Physician's Global Assessment (PGA) Ratings of Excellent or Cleared at Week 24 | 46.0 percentage of subjects |