Study of Therapeutic Options for Subjects Discontinuing Efalizumab and Experiencing Disease Recurrence

A Phase IV Open Label, Multicentre, Investigational Study of the Therapeutic Options for Subjects Discontinuing Efalizumab Therapy and Experiencing Inflammatory Disease Recurrence

This is a pilot investigational study of the appropriate therapeutic regimens to treat subjects experiencing inflammatory recurrence (rebound) of psoriatic disease upon discontinuation of efalizumab therapy and of the biological mechanisms involved in inflammatory disease recurrence and control.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Cyclosporins; Drug: Retinoids; Drug: Systemic corticosteroids; Drug: Methotrexate; Drug: Systemic corticosteroids/methotrexate

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participation in Genentech study ACD2601g, Genentech study HUPA 600 or Serono study IMP24011.
• Inflammatory psoriasis disease recurrence occurring up to 2 months after discontinuation of efalizumab that required immediate therapeutic control in the opinion of the Investigator. Psoriasis had to be rapidly developing, symptomatic and inflammatory in nature.
• Written informed consent, given prior to any study-related procedure not part of the subject's normal medical care, with the understanding that the subject could withdraw consent at any time without prejudice to his or her future medical care.

• Female subjects had to be neither pregnant nor breast-feeding, and had to lack childbearing potential, as defined by either:

  • Being post-menopausal or surgically sterile, or
  • Using an accepted form of contraception.
• Confirmation that the subject was not pregnant had to be established by a negative urinary hCG test at SD1. A pregnancy test was not required if the subject was post-menopausal or surgically sterile.
• Outpatient status at the time of enrolment.

Exclusion Criteria:

• Disease recurrence that was part of the natural disease progression, was not inflammatory in nature, and was not related to efalizumab study medication in the previous study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporin; Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Drug: Cyclosporins; Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.
Experimental: Retinoids; Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Drug: Retinoids; Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.
Experimental: Systemic corticosteroids; Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Drug: Systemic corticosteroids; Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.
Experimental: Methotrexate; Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Drug: Methotrexate; Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.
Experimental: Systemic corticosteroids/methotrexate; Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.	Drug: Systemic corticosteroids/methotrexate; Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physician's Global Assessment (PGA) of Change Over Time (Good or Better)	The PGA response was classified according to the following categories by changes in all clinical signs and symptoms as compared to baseline: Cleared: Remission except for residual manifestations such as mild erythema (100% improvement) Excellent: Improvement of 75%-99% except for residual manifestations such as mild erythema Good: Improvement of 50%-74%	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Global Psoriasis Assessment (PGPA)	The PGPA consisted of a single self-explanatory item: On a scale from 0 to 10, with 0 being no psoriasis and 10 the worst psoriasis that you can imagine, please rate the state of your psoriasis right now. Note: Consider only your skin condition and do not consider other aspects that may be related to your psoriasis (such as psoriatic arthritis).	12 weeks

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Patrick Natta, MD, Merck Serono SA

Publications and helpful links

General Publications

• Papp KA, Toth D, Rosoph L, on behalf of the 25180 study group. Approaches to discontinuing efalizumab: results of an open-label study comparing different transitioning therapies. Abstract for presentation at EADV2005, Sofia, Bulgaria, 19-22 May 2005

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): April 1, 2005

Study Registration Dates

• First Submitted: March 2, 2010
• First Submitted That Met QC Criteria: March 2, 2010
• First Posted (Estimate): March 3, 2010

Study Record Updates

• Last Update Posted (Estimate): February 27, 2014
• Last Update Submitted That Met QC Criteria: January 26, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Psoriasis; Discontinuation of efalizumab; Managing inflammatory recurrence
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease Attributes; Skin Diseases, Papulosquamous; Psoriasis; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Methotrexate; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 25180