Clinical trial NCT00972543: Raptiva in Palm and Sole Psoriasis
Official title: A Phase IV Multicentre, Randomized Double-blind, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Raptiva in the Treatment of Subjects With Moderate to Severe Chronic Plaque Psoriasis Involving Palms and/or Soles, With or Without Pustules.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Plaque Psoriasis
Keywords: Moderate to severe chronic plaque psoriasis
palms and/or soles
with or without pustules
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-09-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI)
timeFrame: Measured at Screening, Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Static Physician Global Assessment Hands and Feet (sPGA - H&F)
timeFrame: Measured at Screening, Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20 visits and Early Termination Visit
measure: Psoriasis Area and Severity Index (PASI)
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Static Physician Global Assessment (SPGA)
timeFrame: Measured at Screening, Day 0 and Day 7
measure: Dynamic Physician's Global Assessment of Change (dPGA)
timeFrame: Measured at Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
Secondary outcomes:
measure: Participants With Direct Physical Examination Abnormalities
timeFrame: Measured at at screening, Day 0, Week 4, Week 12, and Early Termination visits
measure: Complaint Directed Physical Examinations
timeFrame: Measure at (Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits)
measure: Heart Rate
timeFrame: Measure at Day 0, Day 7, Week 8, Week 16 and Follow Up and Early Termination visits
measure: Arterial Blood Pressure
timeFrame: Measure at Day 0, Day 7, Week 8, Week 16 and Follow Up and Early Termination visits
measure: Temperature
timeFrame: Measure at Day 0, Day 7, Week 8, Week 16 and Follow Up and Early Termination visits
measure: Weight Measurements
timeFrame: Measured at Screening, Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Haemoglobin
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Haematocrit
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Red Cell Count
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - White Cell Count
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Platelets
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Neutrophils
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Lymphocytes
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Monocytes
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Eosinophils
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Haematology Laboratory Assessments - Basophils
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Sodium
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Potassium
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Urea
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Creatinine
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Total Bilirubin
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Total Protein
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Calcium
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Aspartate Transaminase
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Alanine Transaminase
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Gamma Glutamyl Transpeptidase
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - Alkaline Phosphatase
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Clinical Chemistry Laboratory Assessments - C Reactive Protein
timeFrame: Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
measure: Negative Serum Human Chorionic Gonadotrophin (hCG) Pregnancy Test
timeFrame: Measured at screening (Day -14 to Day -1)
measure: Negative Urinary Human Chorionic Gonadotrophin (hCG) Pregnancy Test
timeFrame: Measured at screening (Day -14 to Day -1)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Serono S.A., Geneva
name: Nicole Selenko-Gebauer, MD
role: STUDY_DIRECTOR
References: