Psoriasis
Conditions
Keywords
Candidates for systemic therapy for psoriasis
Brief summary
This is a Phase IIIb/IV, open label, multicentre study of efalizumab (anti cluster of differentiation \[CD\] 11a recombinant human monoclonal antibody) in participants with moderate to severe plaque psoriasis who have failed to respond to, have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate, and psoralen and ultraviolet A phototherapy (PUVA).
Interventions
DRUGEfalizumab - anti-CD11a recombinant human monoclonal antibody
Participants will receive efalizumab 1.0 milligram per kilogram (mg/kg) (with an initial conditioning dose of 0.7 mg/kg) once weekly by subcutaneous injection for 12 weeks (first treatment \[FT\]). Depending on the response at Week 12, participants could receive additional 8 to 12 weekly injections of efalizumab 1.0 mg/kg.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate to severe plaque psoriasis participants who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA * Age at least 18 years * 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 and up to 3 months after the last dose of efalizumab * Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care * Discontinuation of any systemic psoriasis treatment prior to commencement of the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 (efalizumab) * Discontinuation of all biologic agents (other than efalizumab) 3 months prior to receiving first dose of study drug (efalizumab) * Discontinuation of any investigational drug or treatment 3 months prior to Study Day 0 or as per washout requirements from previous protocol * No primary vaccinations (e.g., tetanus, booster, influenza vaccine) at least 14 days prior to first dose of study drug * The participant must be willing and able to comply with the protocol requirements for the duration of the study
Exclusion criteria
* Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis * Participants who have previously been on efalizumab treatment who withdrew due to lack of efficacy or an adverse event. If withdrawal 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 (eg, systemic fungal infections, parasites) * Seropositivity for human immunodeficiency virus (HIV). Participants will undergo mandatory testing at screening. Participants who are positive for HIV will be excluded * Pregnancy or breast feeding * White Blood Cell (WBC) count less than (\<) 4\*10\^9 per liter or greater than (\>) 14\*10\^9 per liter * Participants with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count \<100\*10\^9 per liter * Seropositivity for hepatitis B or C virus. Participants will undergo testing at screening. Participants who are positive for hepatitis B antigen or hepatitis C antibody will be excluded * 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 participants. Participants with a positive chest X-ray will be excluded * Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Participants with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled * Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year * Any medical condition that, in the judgment of the investigator, would jeopardize the participant's safety following exposure to study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Physician's Global Assessment (PGA) Ratings of Good or Better (FT) | Week 12 | The PGA assesses the global response of all psoriatic lesions to therapy by comparing the participant's present condition to baseline. PGA response includes: Cleared (100 percent \[%\] improvement; remission of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Excellent (75% to 99% improvement of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Good (50% to 74% improvement of all clinical signs and symptoms); Fair (25% to 49% improvement of all clinical signs and symptoms); Slight (1% to 24% improvement of all clinical signs and symptoms); Unchanged (clinical signs and symptoms unchanged); Worse (clinical signs and symptoms deteriorated). Percentage of participants with PGA ratings of Good or Better (i.e, Good, Excellent or Cleared) are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Psoriasis Rebound | Up to 8 weeks after end of FT (up to Week 20) | Rebound was defined as worsening of disease as assessed by Psoriasis Area and Severity Index (PASI) score \>125% of baseline or new pustular, erythrodermic, or more inflammatory psoriasis occurring within 2 months of stopping therapy. PASI is an instrument used to assess the extent of cutaneous psoriasis and to measure the effects of therapy. The PASI divides the body into four anatomical regions: head, trunk, upper limbs, and lower limbs. For each region, the evaluator assesses the severity of erythema, induration/thickness and scaling and determines the percentage of the region affected by disease. A numerical PASI score is derived that evaluates the severity of symptoms in terms of the total body surface area affected. Total PASI score ranges from 0 to 72, with higher scores indicating more severe disease. |
| Percentage of Participants With Psoriasis Exacerbation | During study (40 weeks) | Exacerbation was defined as disease worsening either during or after treatment which was more inflammatory in nature compared to baseline and occurred either within pre-existing plaques, at previously uninvolved sites, or as new morphologies of disease. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Efalizumab Participants received efalizumab 1.0 mg/kg (with an initial conditioning dose of 0.7 mg/kg) once weekly by subcutaneous injection for 12 weeks (FT). Depending on the response at Week 12, participants could have received additional 8 to 12 weekly injections of efalizumab 1.0 mg/kg. | 1,255 |
| Total | 1,255 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 81 |
| Overall Study | Did Not Provide Post-Baseline Data | 11 |
| Overall Study | Lack of Efficacy | 52 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Other | 27 |
| Overall Study | Protocol Violation | 3 |
Baseline characteristics
| Characteristic | Efalizumab |
|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 395 Participants |
| Sex: Female, Male Male | 860 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 623 / 1,266 |
| serious Total, serious adverse events | 60 / 1,266 |
Outcome results
Primary
Percentage of Participants With Physician's Global Assessment (PGA) Ratings of Good or Better (FT)
The PGA assesses the global response of all psoriatic lesions to therapy by comparing the participant's present condition to baseline. PGA response includes: Cleared (100 percent \[%\] improvement; remission of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Excellent (75% to 99% improvement of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Good (50% to 74% improvement of all clinical signs and symptoms); Fair (25% to 49% improvement of all clinical signs and symptoms); Slight (1% to 24% improvement of all clinical signs and symptoms); Unchanged (clinical signs and symptoms unchanged); Worse (clinical signs and symptoms deteriorated). Percentage of participants with PGA ratings of Good or Better (i.e, Good, Excellent or Cleared) are reported.
Time frame: Week 12
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efalizumab | Percentage of Participants With Physician's Global Assessment (PGA) Ratings of Good or Better (FT) | 68.0 percentage of participants |
Secondary
Percentage of Participants With Psoriasis Exacerbation
Exacerbation was defined as disease worsening either during or after treatment which was more inflammatory in nature compared to baseline and occurred either within pre-existing plaques, at previously uninvolved sites, or as new morphologies of disease.
Time frame: During study (40 weeks)
Population: ITT population. Here, overall number of participants analyzed = participants who failed to respond (PGA less than good) at Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efalizumab | Percentage of Participants With Psoriasis Exacerbation | 12.9 percentage of participants |
Secondary
Percentage of Participants With Psoriasis Rebound
Rebound was defined as worsening of disease as assessed by Psoriasis Area and Severity Index (PASI) score \>125% of baseline or new pustular, erythrodermic, or more inflammatory psoriasis occurring within 2 months of stopping therapy. PASI is an instrument used to assess the extent of cutaneous psoriasis and to measure the effects of therapy. The PASI divides the body into four anatomical regions: head, trunk, upper limbs, and lower limbs. For each region, the evaluator assesses the severity of erythema, induration/thickness and scaling and determines the percentage of the region affected by disease. A numerical PASI score is derived that evaluates the severity of symptoms in terms of the total body surface area affected. Total PASI score ranges from 0 to 72, with higher scores indicating more severe disease.
Time frame: Up to 8 weeks after end of FT (up to Week 20)
Population: Observation population included all participants had stopped treatment with efalizumab following the FT (Week 12) and who had responded to treatment during (PGA good or better ) FT. Here, overall number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efalizumab | Percentage of Participants With Psoriasis Rebound | 11.0 percentage of participants |