Raptiva in Palm and Sole Psoriasis
Condition: Chronic Plaque Psoriasis
MeSH terms: Psoriasis
Intervention: Efalizumab (Raptiva); Placebo
Intervention description: Double-blind phase 0.7mg/kg subcutaneously (sc), followed by 1mg/kg/wk sc for 12 weeks.
Open label extension 0.7mg/kg sc Raptiva followed by 1mg/kg/wk sc for a further 12 weeks.; Double-blind phase sc Placebo for 12 weeks. Open label extension 0.7mg/kg sc Raptiva followed by 1mg/kg/wk sc for a further 12 weeks.
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Moderate to severe chronic plaque psoriasis; palms and/or soles; with or without pustules

Summary:

      The primary purpose of the study is to evaluate the safety and efficacy of Raptiva® compared
      to placebo in controlling moderate to severe chronic plaque psoriasis involving palms and/or
      soles scoring Palmo-plantar Pustular Psoriasis Area and Severity Index (PPPASI) ≥5 in
      subjects that are candidates for phototherapy or systemic therapies.

      The rational of the trial is that psoriasis involving palms and/or soles is a painful
      condition associated with fissuring, scaling and in some instances with pustulation. Because
      of its localization, it is a disabling condition that limits dexterity and affects social
      interaction, leading to compromised quality of life; and this confers additional severity to
      that of plaque psoriasis on the body. The therapeutic approach for palm and sole plaque-type
      psoriasis usually begins with topical corticosteroid treatment. If the disease reaches a
      certain extent, the next step involves the addition of systemic treatments. Substances like
      methotrexate, retinoids and cyclosporine have shown to be efficacious, but their long-term
      usage is often limited by toxicity. Biologic treatments for psoriasis avoid this toxicity and
      offer a new therapeutic approach.

      The therapeutic potential of Raptiva® to treat palm and sole psoriasis refractory to systemic
      treatments has been described in numerous case reports and in one placebo-controlled phase IV
      study. However, in all cases, the number of subjects included was low, and in most cases the
      trials were not prospectively designed.

      Since the efficacy of Raptiva® on psoriasis of palms and soles must be determined using the
      validated PPPASI measure, it is necessary for scientific and ethical reasons to include a
      placebo arm during the first 12 weeks. Finally, as the clinical response may sometimes take
      longer than 12 weeks, subjects must be treated and evaluated during an additional 12-week
      open-label extended treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

        To be eligible for inclusion into this trial, the subjects must fulfill all of the
        following criteria:

          1. Subjects must have moderate to severe chronic (disease history of at least 6 months
             from diagnosis) plaque psoriasis involving the palms and/or soles (PPPASI =/>5) at
             screening, and must be candidates for phototherapy and systemic therapies.

          2. Subjects must be outpatients.

          3. Subjects must have stable disease at study entry (i.e. no exacerbation of psoriasis
             during the screening period).

          4. Subjects must not have received any systemic psoriasis medication at least 14 days
             prior to the first administration of investigational medicinal product.

          5. Subjects must not have received any topical psoriasis medication at least 14 days
             prior to the first administration of investigational medicinal product (emollients are
             allowed, as well as low potency steroids to the face and/or groin).

          6. Subjects must be at least 18 years old at the time that the informed consent is
             obtained.

          7. Female subjects of childbearing potential must use an adequate method of contraception
             to prevent pregnancy and must agree to continue to practice adequate contraception for
             the duration of their participation in the study (up to the last safety follow up
             visit). For male subjects, it is mandatory to practice birth control during
             participation in the trial, as there are no data on the effect of Raptiva® on
             spermatogenesis. For the purposes of this trial, women of childbearing potential are
             defined as "All female subjects after puberty unless they are post-menopausal for at
             least two years, are surgically sterile or are sexually inactive." Adequate
             contraception is defined as two barrier methods, or one barrier method with
             spermicide, or an intrauterine device or use of the oral female contraceptive.

          8. Subjects must have discontinued all biological agents at least 3 months prior to the
             first study treatment injection.

          9. Subjects must have discontinued any investigational drug or treatment at least 3
             months prior to study Day 0 and/or as per washout requirements from previous protocol.

         10. Subjects must be willing and able to comply with the protocol requirements for the
             duration of the study.

         11. Subjects must have provided their written informed consent, prior to any study-related
             procedure not part of normal medical care, with the understanding that consent

        Exclusion Criteria:

        To be eligible for inclusion in this trial, the subjects must not meet any of the following
        criteria:

          1. Hypersensitivity to Raptiva®/matching placebo or to any of their excipients.

          2. Current use of any prohibited therapy (systemic or topical treatments for psoriasis,
             such as retinoids; immunosuppressive drugs such as methotrexate, cyclosporine A,
             azathioprine, or mycophenolate mofetil, or any other experimental drug).

          3. Previous or current exposure to Raptiva®.

          4. History of or ongoing alcohol or drug abuse.

          5. History of or ongoing opportunistic infection or other serious infection. This
             includes any infections from the following list: Pneumocystis carinii, cytomegalovirus
             organ infections, Candida albicans (excluding simple localised muco-cutaneous
             infections), mycobacterium infections, Cryptococcus neoformans, Toxoplasma gondii,
             herpes simplex (excluding localised oral or genital muco-cutaneous infection), herpes
             zoster (excluding simple shingle eruption), cryptosporidium, Isospora belli,
             coccidioidomycosis, aspergillosis, histoplasmosis, and nocardiosis. This also includes
             diagnoses requiring more than 2 weeks of therapy, such as endocarditis and
             osteomyelitis treated in the past 6 months. In addition, if the subject is currently
             receiving antibiotics, antivirals, or antifungals for an infection or for suppression
             of 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; any
             subjects who are found to be seropositive for hepatitis B antigen, hepatitis C
             antibody, or HIV will be excluded, and proper diagnosis and further therapy will be
             recommended.

          7. Presence of active tuberculosis.

          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 or presence 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%, a haemoglobin (Hgb) level <11 g/dL, or 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 vaccine within the 14 days prior to the
             first dose of investigational medicinal product.

         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 form of psoriasis.

         16. Immunodeficiencies.

         17. Signs and symptoms suggestive of transmissible spongiform encephalopathy or family
             history of such.