Safety and Efficacy of Adalimumab in Patients Who Showed an Unsatisfactory Response to Etanercept

• ClinicalTrials.gov Identifier: NCT00927069
• Recruitment Status: Completed
• First Posted: June 24, 2009
• Results First Posted: August 24, 2010
• Last Update Posted: September 9, 2011
• Sponsor: Innovaderm Research Inc.
• Collaborator: Abbott
• Information provided by (Responsible Party): Innovaderm Research Inc.

Study Description

Brief Summary:

This study will provide data on additional therapeutic benefits in administering Adalimumab in patients with plaque psoriasis that showed an unsatisfactory response after at least 3 months of treatment with etanercept.

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Drug: Adalimumab every other week; Drug: Adalimumab Every Week	Phase 3

Detailed Description:

A total of 50 patients with psoriasis vulgaris who showed an unsatisfactory response to etanercept 50 mg twice a week followed by 50 mg once a week and a total of 50 patients who showed an unsatisfactory response to etanercept 50 mg twice a week without dose reduction will be recruited. All patients will receive adalimumab 40 mg every other week (EOW) for 12 weeks. Patients who fail to reach a physician's global assessment (PGA) of clear or almost clear at week 12 will have an increase in adalimumab to 40 mg every week (EW) for an additional 12 weeks. Patients who reach a PGA of clear or almost clear at week 12 will continue to receive adalimumab at 40 mg EOW for an additional 12 weeks. Patients will be evaluated for safety and efficacy every 4 weeks for a total of 24 weeks. PASI, BSA and PGA will be performed at each visit. Routine chemistry, hematology and urinalysis will be performed every 4 weeks.

The percentage of patients achieving a physician's global assessment (PGA) of clear or almost clear after at least 12 weeks of adalimumab will be calculated for patients who had shown an unsatisfactory response to 3 months of etanercept at 50 mg twice a week without dose reduction as well as for patients who had shown an unsatisfactory response to 3 months of etanercept at 50 mg twice a week followed by 50 mg once a week.

A physician's global assessment (PGA) of clear is defined by no plaque elevation over normal skin. There is no scale. Erythema is perceptible as hyperpigmentation, pigmented macules, diffuse faint pink or red coloration.

A physician's global assessment (PGA) of almost clear is defined as follows: It is possible but difficilt to ascertain whether there is a slight elevation above normal skin. There is scaling in the form of surface dryness with some white coloration. Erythema is up to a definite red coloration.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Study to Evaluate the Efficacy and Safety of Adalimumab in Patients With Plaque Psoriasis Who Showed an Unsatisfactory Response to Etanercept
• Study Start Date: March 2007
• Actual Primary Completion Date: September 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; Patients who have shown an unsatisfactory response to 3 months of etanercept 50 mg twice a week without dose reduction prior to screening.	Drug: Adalimumab every other week; Adalimumab 40mg injection every other week for 24 weeks; Other Name: HUMIRA
Experimental: Group B; Patients who showed a satisfactory response to 3 months or more of etanercept 50 mg twice a week followed by a loss of response after dose reduction to 50 mg etanercept once a week prior to screening.	Drug: Adalimumab every other week; Adalimumab 40mg injection every other week for 24 weeks; Other Name: HUMIRA
Experimental: Group A dose increase at Week 12; Patients in group A who - after 12 weeks of adalimimab 40 mg every other week in this study - failed to reach a physician's global assessment (PGA) of clear or almost clear and had a dose increase to 40 mg adalimimab every week for another 12 weeks.	Drug: Adalimumab Every Week; Adalimumab 40mg injection every week for the last 12 weeks of study.; Other Name: HUMIRA
Experimental: Group B dose increase at Week 12; Patients in group B who - after 12 weeks of adalimimab 40 mg every other week in this study - failed to reach a physician's global assessment (PGA) of clear or almost clear and had a dose increase to 40 mg adalimimab every week for another 12 weeks.	Drug: Adalimumab Every Week; Adalimumab 40mg injection every week for the last 12 weeks of study.; Other Name: HUMIRA

Outcome Measures

Primary Outcome Measures :

1. Number of Patients From Group B Who Achieve a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12. [ Time Frame: 12 weeks ]

   Efficacy of adalimumab 40 mg every other week in patients in Group B by calculating the number of patients who achieve a PGA of clear or almost clear at Week 12.

   Clear is defined by no plaque elevation above normal skin. There is no scale. Erythema is perceptible as hyperpigmentation, pigmented macules, diffuse faint pink or red coloration.

   Almost Clear is defined as follows: It is possible but difficult to ascertain whether there is a slight elevation above normal skin. There is scaling in the form of surface dryness with some white coloration. Erythema is up to a difinite red coloration.

Secondary Outcome Measures :

1. Number of Patients From Group A Who Achieve a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 12. [ Time Frame: 12 weeks ]

   Efficacy of adalimumab in patients from Group A who achieve a Physician's Global Assessment (PGA) of clear or almost clear at week 12.

   Clear is defined by no plaque elevation above normal skin. There is no scale. Erythema is perceptible as hyperpigmentation, pigmented macules, diffuse faint pink or red coloration.

   Almost Clear is defined as follows: It is possible but difficult to ascertain whether there is a slight elevation above normal skin. There is scaling in the form of surface dryness with some white coloration. Erythema is up to a difinite red coloration.

2. Number of Patients From Group B Who Achieve a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 24 After a Dose Increase to 40mg Adalimumab Every Week. [ Time Frame: 24 weeks ]

   Efficacy of adalimumab in patients from Group B who achieve a Physician's global assessment (PGA) of clear or almost clear at Week 24.

   Clear is defined by no plaque elevation above normal skin. There is no scale. Erythema is perceptible as hyperpigmentation, pigmented macules, diffuse faint pink or red coloration.

   Almost Clear is defined as follows: It is possible but difficult to ascertain whether there is a slight elevation above normal skin. There is scaling in the form of surface dryness with some white coloration. Erythema is up to a difinite red coloration.

3. Number of Patients From Group A Who Achieve a Physician's Global Assessment (PGA) of Clear or Almost Clear at Week 24 After a Dose Increase to 40mg Adalimumab Every Week. [ Time Frame: 24 weeks ]

   Efficacy of adalimumab in patients from Group A who achieve a Physician's Global Assessment (PGA) of clear or almost clear at Week 24.

   Clear is defined by no plaque elevation above normal skin. There is no scale. Erythema is perceptible as hyperpigmentation, pigmented macules, diffuse faint pink or red coloration.

   Almost Clear is defined as follows: It is possible but difficult to ascertain whether there is a slight elevation above normal skin. There is scaling in the form of surface dryness with some white coloration. Erythema is up to a difinite red coloration.

4. Total Number of Adverse Events for All Patients in the Study. [ Time Frame: 24 weeks ]
   Safety of adalimumab in patients with plaque psoriasis that showed an unsatisfactory response after at least 3 months of therapy with etanercept

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subject with plaque psoriasis with documentation of an unsatisfactory response to etanercept as defined by either:

  1. Failure to present a PGA of clear or almost clear after at least 3 months of etanercept at 50 mg twice a week OR;
  2. Failure to present a PGA of clear or almost clear after at least 3 months of etanercept at 50 mg twice a week followed by a dose reduction to 50 mg once a week. To be eligible these patients must have reached a PGA of clear or almost clear after at least 3 months of etanercept at 50 mg twice a week followed by a loss of PGA of clear or almost clear at anytime after a dose reduction to 50 mg of etanercept once a week.
• Subject presents a PGA of 3 or more at baseline visit.
• Subject with plaque psoriasis at screening that is severe enough to be candidate for systemic therapy.
• Subject is 18 to 80 years of age .

• Female subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion:

  1. condoms, sponge, foams, jellies, diaphragm or IUD;
  2. contraceptives (oral or parenteral) for three months prior to study drug administration;
  3. a vasectomized partner;
• Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit.
• Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, and CXR performed at Screening.
• Subjects will be evaluated for latent TB infection with a PPD test and CHX. Subjects who demonstrate evidence of latent TB infection (either PPD more than or equal to 5 mm of induration, irrespective of BCG vaccination status and negative CXR findings for active TB, and/or suspicious CXR findings will not be allowed to participate in the study.
• Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
• Subjects must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections.

Exclusion Criteria:

• Subject has other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis or with subject's safety.
• Subject has a history of an allergic reaction or significant sensitivity to constituents of study drug, including latex (a component of the pre-filled syringe).
• Subject who has used topical treatments in the last 4 weeks of the etanercept treatment period when the response to etanercept was evaluated as unsatisfactory must use the same topical therapy with the same agents applied in the same manner and with the same application frequency for two weeks prior to the baseline visit as well as during the entire trial. The use of any other topical treatment for psoriasis is prohibited except for allowed treatments.
• Subject who has used UVB phototherapy, excessive sun exposure, phototherapy or any non-biological systemic therapy for the treatment of psoriasis less than 30 days before day 0. Investigational chemical agents must be discontinued at least 30 days or 5 half-lives prior to the Baseline visit (whichever is longer).
• Subject who has used any biological therapy (apart from etanercept) for the treatment of psoriasis less than 3 months (90 days) before day 0. Etanercept must be discontinued before baseline but a washout period is not required.
• Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
• Subjects for whom documentation of unsatisfactory response to etanercept was obtained while the subject was under combination treatment with any of the following: UVB phototherapy, PUVA therapy, prednisone, methotrexate, acitretin, cyclosporine or any other systemic or biologic drug (apart from etanercept).
• Subject has a poorly controlled medical condition, such as uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent stroke and any other condition which, in the opinion of the investigator, would put the subject at risk if participating in the study.
• Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease.
• Subject has history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix.
• Subject has a history of listeriosis, treated or untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives within 30 days or oral anti-infectives within 14 days prior to the Baseline visit.
• Subject who has received any live attenuated vaccine 28 days or less before baseline.
• Subject with hepatitis B or hepatitis C viral infection.
• Subject with any of the following: hemoglobin ≤ 10 g/L, white blood cells ≤ 3.0 X 109/L, platelet counts ≤130 X 109/L, ALT ≥ 2 times the upper limit of normal, AST ≥ 2 times the upper normal limit, total bilirubin ≥ 2 times the upper normal limit or creatinine ≥ 150 mmol/L.
• Subject currently uses or plans to use anti-retroviral therapy at any time during the study.
• Subject is known to have immune deficiency or is immunocompromised.
• Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or for 150 days after the last dose of study medication.
• Subject has a history of clinically significant drug or alcohol abuse in the last year.
• Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Subject has erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.

Contacts and Locations

Locations

Canada, Manitoba

Winnipeg Clinic

Winnipeg, Manitoba, Canada, R3C 0N2

Canada, Newfoundland and Labrador

NewLab Clinical Research

St-John's, Newfoundland and Labrador, Canada, A1C 2H5

Canada, Ontario

Mediprobe Research

London, Ontario, Canada, N5X 2P1

The Guenther Dermatology Research center

London, Ontario, Canada, N6A 3H7

Lynderm Research

Markham, Ontario, Canada, L3P 1A8

Entralogix Inc.

Oakville, Ontario, Canada, L6K 1E1

Entralogix Clinical Group Inc.

Toronto, Ontario, Canada, M4V 1R1

Windsor Clinical Research Inc.

Windsor, Ontario, Canada, N8W 5L7

Canada, Quebec

Innovaderm Research Laval Inc.

Laval, Quebec, Canada, H7S 2C6

Innovaderm Research Inc

Montreal, Quebec, Canada, H2K 4L5

Centre de Recherches Dermatologiques du Quebec Metropolitain

Ste-Foy, Quebec, Canada, G1V 4X7

Canada

Centre de Recherche Clinique Martin Gilbert inc et Centre Dermatologie Maizerets

Quebec, Canada, G1J 1X7

Sponsors and Collaborators

Innovaderm Research Inc.

Abbott

Investigators

• Principal Investigator: Robert Bissonnette, MD; Innovaderm Research Inc.

More Information

• Responsible Party: Innovaderm Research Inc.
• ClinicalTrials.gov Identifier: NCT00927069
• Other Study ID Numbers: Inno-6002
• First Posted: June 24, 2009
• Results First Posted: August 24, 2010
• Last Update Posted: September 9, 2011
• Last Verified: September 2011

Keywords provided by Innovaderm Research Inc.:

Adalimumab

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Adalimumab; Anti-Inflammatory Agents; Antirheumatic Agents