Raptiva in Palm and Sole Psoriasis

Phase 4

Terminated

• Conditions: Chronic Plaque Psoriasis

• Registration Number: NCT00972543
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09
• Primary Completion: 2009-05
• Study First Submitted: 2009-09-04
• Study First Submitted QC: 2009-09-04
• Study First Posted: 2009-09-07
• Results First Submitted: 2010-06-28
• Results First Submitted QC: 2010-08-04
• Results First Posted: 2010-09-02
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-20
• Last Update Posted: 2014-02-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Psoriasis Area and Severity Index (PASI)	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Minimum possible score 0, maximum possible score 72.
Static Physician Global Assessment (SPGA)	Measured at Screening, Day 0 and Day 7	The global response of all psoriatic lesions to therapy compared with the baseline condition using Study Day 0 Body Diagrams will be evaluated using the following categories: Cleared (100% improvement), Excellent (75-99 improvement), Good (50-74% improvement), Fair (25-49% improvement), Slight (1-24% improvement), Unchanged, or Worse
Dynamic Physician's Global Assessment of Change (dPGA)	Measured at Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	The global response of all psoriatic lesions to therapy compared with the baseline condition using Study Day 0 Body Diagrams will be evaluated using the following categories: Cleared (100% improvement), Excellent (75-99 improvement), Good (50-74% improvement), Fair (25-49% improvement), Slight (1-24% improvement), Unchanged, or Worse
Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI)	Measured at Screening, Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Minimum possible score 0, maximum possible score 72.
Static Physician Global Assessment Hands and Feet (sPGA - H&F)	Measured at Screening, Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20 visits and Early Termination Visit	Minimum possible score 0, maximum possible score 4.

Secondary Outcome Measures

Name	Time	Method
Participants With Direct Physical Examination Abnormalities	Measured at at screening, Day 0, Week 4, Week 12, and Early Termination visits	Physical examination included Lymph node palpation, Abdominal palpation, Auscultation of the lung, heart and intestinum
Complaint Directed Physical Examinations	Measure at (Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits)	Number of participants undergoing complaint directed physical examinations
Heart Rate	Measure at Day 0, Day 7, Week 8, Week 16 and Follow Up and Early Termination visits
Arterial Blood Pressure	Measure at Day 0, Day 7, Week 8, Week 16 and Follow Up and Early Termination visits
Haematology Laboratory Assessments - Platelets	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Temperature	Measure at Day 0, Day 7, Week 8, Week 16 and Follow Up and Early Termination visits
Weight Measurements	Measured at Screening, Day 0, Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits
Haematology Laboratory Assessments - Haemoglobin	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Haematocrit	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Red Cell Count	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - White Cell Count	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Neutrophils	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Lymphocytes	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Monocytes	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Eosinophils	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Haematology Laboratory Assessments - Basophils	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Sodium	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Potassium	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Urea	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Gamma Glutamyl Transpeptidase	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Creatinine	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Total Bilirubin	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Total Protein	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Calcium	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Aspartate Transaminase	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Alanine Transaminase	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - Alkaline Phosphatase	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Clinical Chemistry Laboratory Assessments - C Reactive Protein	Measured at Screening, Day 0, Week 4, Week 8, Week 12, Week 16, Week 20, and Early Termination visits	Participants with abnormal laboratory values considered by the Investigator to be clinically significant reported as adverse events.
Negative Serum Human Chorionic Gonadotrophin (hCG) Pregnancy Test	Measured at screening (Day -14 to Day -1)	A serum human chorionic gonadotrophin (hCG) pregnancy test will be conducted for all female subjects of childbearing potential prior to entering the study.
Negative Urinary Human Chorionic Gonadotrophin (hCG) Pregnancy Test	Measured at screening (Day -14 to Day -1)	A urinary human chorionic gonadotrophin (hCG) pregnancy test will be conducted for all female subjects of childbearing potential prior to entering the study.