Safety and Efficacy of Combining nbUVB to Etanercept in Patients

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Innovaderm Research Inc.
ClinicalTrials.gov Identifier:
NCT00640393
First received: March 18, 2008
Last updated: September 1, 2011
Last verified: September 2011
  Purpose

This study will provide data on the addition of narrow band ultra violet B (nbUVB) phototherapy to participants who have not shown an excellent response to three months of etanercept.


Condition Intervention Phase
Psoriasis Vulgaris
Drug: Etanercept
Device: nbUVB
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Study Combining Etanercept and Short Courses of Narrow-Band UVB in Patients With Psoriasis Vulgaris

Resource links provided by NLM:


Further study details as provided by Innovaderm Research Inc.:

Primary Outcome Measures:
  • Number of Participants Attaining a 90 Percent Reduction in PASI From Baseline (PASI 90) - ITT [ Time Frame: 112 and 140 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst



Secondary Outcome Measures:
  • Number of Participants Attaining a 75 Percent Reduction in PASI From Baseline (PASI 75) - ITT [ Time Frame: 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 100% Reduction in PASI From Baseline (PASI 100) - ITT [ Time Frame: 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 50% Reduction From Baseline in PASI From Baseline (PASI-50) - ITT [ Time Frame: 28 and 84 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 75 % Reduction in PASI From Baseline (PASI-75) - ITT [ Time Frame: 28 and 84 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 90 Percent Reduction in PASI From Baseline (PASI-90) - ITT [ Time Frame: 28 and 84 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 100 Percent Reduction in PASI From Baseline (PASI-100) - ITT [ Time Frame: 28 and 84 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Patients Attaining a PGA (Physician's Global Assessment) of 0 or 1 - ITT [ Time Frame: 0, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Number of patients attaining a Physician's Global Assessment (PGA) of clear (0) or minimal (1).

    PGA scores are evaluated at each time point.

    The degree of overall lesion severity at the time of the physician's evaluation of the patient evaluated using the following scale:

    • 0 = clear
    • 1 = minimal
    • 2 = mild
    • 3 = moderate
    • 4 = severe
    • 5 = very severe

    The scale evaluates plaque elevation, scaling and erythema.


  • Body Surface Area (BSA) Affected by Psoriasis - ITT [ Time Frame: 0, 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    BSA scores are evaluated at each time point.

    BSA is a measure of the percentage of body surface affected by psoriasis.


  • Dermatology Life Quality Index (DLQI) - ITT [ Time Frame: 0, 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    The aim of this questionnaire is to measure how much one's skin problem has affected one's life over the week prior to the visit.

    Questionnaire is patient-assessed (self-reported). DLQI scores are evaluated at each time point.

    Scale is from 0 best to 30 worst.

    0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life


  • Number of Adverse Drug Reactions - ITT [ Time Frame: 196 days ] [ Designated as safety issue: Yes ]

    Evaluation of safety of etanercept and nbUVB as compared to etanercept alone by reporting the incidence rates of adverse drug reactions.

    Definition: A response to a drug that is noxious and unintended and that occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function.

    Only adverse drug reactions that were at least possibly related to etanercept were recorded. All symptoms observed at the injection site such as erythema, burning, edema and pruritus were recorded together as Injection Site Reaction.


  • Number of Infectious Adverse Events - ITT [ Time Frame: 196 days ] [ Designated as safety issue: Yes ]

    Evaluation of safety of etanercept and nbUVB as compared to etanercept alone by reporting the incidence rates of infectious adverse events.

    Definition: An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship with this treatment.

    Only infectious and malignant (including any type of skin cancer) adverse events were recorded.


  • Number of Serious Adverse Events - ITT [ Time Frame: 196 days ] [ Designated as safety issue: Yes ]

    Evaluation of safety of etanercept and nbUVB as compared to etanercept alone by reporting the incidence rates of serious adverse events.

    Definition: any adverse event from this study that results in one of the following outcomes, or is significant for any other reason:

    • death
    • initial or prolonged inpatient hospitalization
    • a life-threatening experience (that is, immediate risk of dying)
    • persistent or significant disability/incapacity
    • congenital anomaly/birth defect

  • Number of Participants Attaining a 90 Percent Reduction in PASI From Baseline (PASI 90) - PP [ Time Frame: 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 75 Percent Reductionin PASI From Baseline (PASI-75) - PP [ Time Frame: 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Participants Attaining a 100 Percent Reduction in PASI From Baseline (PASI-100) - PP [ Time Frame: 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale:

    • 0 = No symptoms
    • 1 = Slight
    • 2 = Moderate
    • 3 = Marked
    • 4 = Very marked

    The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6.

    Total scale 0 = best and 72 = worst


  • Number of Patients Attaining a PGA (Physician's Global Assessment) of 0 or 1 - PP [ Time Frame: 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    Number of patients attaining a Physician's Global Assessment (PGA) of clear (0) or minimal (1).

    PGA scores are evaluated at each time point.

    The degree of overall lesion severity at the time of the physician's evaluation of the patient evaluated using the following scale:

    • 0 = clear
    • 1 = minimal
    • 2 = mild
    • 3 = moderate
    • 4 = severe
    • 5 = very severe

    The scale evaluates plaque elevation, scaling and erythema.


  • Body Surface Area (BSA) Affected by Psoriasis - PP [ Time Frame: 0, 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    BSA scores are evaluated at each time point.

    BSA is a measure of the percentage of body surface affected by psoriasis.


  • Dermatology Life Quality Index (DLQI) - PP [ Time Frame: 0, 84, 112, 140 and 168 days ] [ Designated as safety issue: No ]

    The aim of this questionnaire is to measure how much one's skin problem has affected one's life over the week prior to the visit.

    Questionnaire is patient-assessed (self-reported). DLQI scores are evaluated at each time point.

    Scale is from 0 best to 30 worst.

    0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life



Enrollment: 99
Study Start Date: April 2008
Study Completion Date: March 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Part 1 - Etanercept
All participants received etanercept 50 mg twice a week for 12 weeks.
Drug: Etanercept
Etanercept 50 mg, subcutaneous (SC) injection.
Other Name: Enbrel
Active Comparator: Part 2 - Etanercept and nbUVB
Participants who did not reach a 90 percent reduction in psoriasis area and severity index (PASI-90) after 12 weeks and were randomized to the narrow band ultra violet B (nbUVB) group. They received nbUVB treatments three times a week and 50 mg Etanercept once per week.
Drug: Etanercept
Etanercept 50 mg, subcutaneous (SC) injection.
Other Name: Enbrel
Device: nbUVB
.
Other Names:
  • narrow band ultra violet B phototherapy
  • narrow band UVB
Active Comparator: Part 2 - Etanercept
Participants who did not reach PASI-90 after 12 weeks and were randomized to the Etanercept group. They received 50 mg Etanercept once per a week.
Drug: Etanercept
Etanercept 50 mg, subcutaneous (SC) injection.
Other Name: Enbrel

Detailed Description:

All participants will receive etanercept 50 mg twice a week for 12 weeks. Participants who reach PASI-90 at Day 84 will be discontinued from the study (they can continue receiving commercial etanercept outside the study). Participants remaining in the study at Day 84 will decrease etanercept to 50 mg weekly for another 12 weeks.

Participants who do not attain a 90 percent reduction in PASI from baseline (PASI-90) after 12 weeks will be randomized (1:1) to receive either etanercept alone or etanercept with short courses of narrow band ultra violet B (nbUVB)phototherapy. Participants randomized to the nbUVB group will receive nbUVB treatments three times a weeks for at least four weeks. At every planned study visit after Day 84, nbUVB treatment will be discontinued in participants who reach PASI-90. nbUVB phototherapy will be re-initiated for another four weeks at the subsequent planned study visit if they lose their PASI-90 response.

Efficacy will be evaluated with PASI, BSA and PGA by a blinded evaluator at Days 0, 28, 84, 112, 140 and 168. The effect of the treatment on quality of life will be evaluated using the DLQI questionnaire at Days 112, 140 and 168. Safety will be evaluated by physical examination and adverse events evaluation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 or older;
  • Patient with moderate to severe plaque psoriasis for whom a decision to use etanercept has been made;
  • At the investigator discretion, patient who would benefit from systemic therapy;
  • PASI (psoriasis area and severity index) ≥ 10 and BSA (body surface area affected by psoriasis) ≥ 10 at day 0;
  • Unless surgically sterile (or at least 1 year post-menopausal for women), abstinent or homosexual, patient (men and women) willing to use adequate contraceptive method for at least 30 days before Day 0 and until one month after the last drug administration;
  • Patient capable of giving informed consent;
  • Patient with normal or non clinically significant chest X ray within six months of screening;
  • Patient with negative purified protein derivative (PPD) within 3 months of Day 0;
  • Negative urine pregnancy test for women of childbearing potential

Exclusion Criteria:

  • Patient used topical steroid, topical tar preparations, or other anti-psoriatic preparations except tar or salicylic acid shampoo or hydrocortisone for the face, scalp, genital and inframammary areas within two weeks of Day 0;
  • Patient with presence of erythrodermic, pustular or a predominantly guttate psoriasis;
  • At the investigator's discretion, patient with any significant infection within 30 days of screening or a patient at risk of septicemia;
  • Patient with evidence of any skin condition that would interfere with the evaluation of psoriasis;
  • Patient used investigational drugs within 12 weeks or three half-life of Day 0 whichever is longer;
  • Patient used systemic anti-psoriatic drugs such as steroids, retinoids, methotrexate, cyclosporine within four weeks of Day 0;
  • Patient used any biologic such as alefacept, etanercept, efalizumab, infliximab and adalimumab within 12 weeks of Day 0;
  • Patient used ultraviolet light therapy (UVB or nbUVB) within four weeks of Day 0 or PUVA (psoralen ultra violet A) within eight weeks of Day 0;
  • Patient with prior or concurrent use of cyclophosphamide;
  • Patient with concurrent sulfasalazine therapy or concurrent use of anakinra;
  • Patient with an unstable or serious medical condition as defined by the investigator or presence of any significant medical condition that might cause this study to be detrimental to the patient.
  • Uncontrolled or severe comorbidities such as diabetes mellitus requiring insulin; congestive heart failure (NYHA (New York Heart Association) class III or IV) or history of myocardial infarction or cerebrovascular accident or transient ischemic attack within three months of screening visit; unstable angina pectoris; uncontrolled hypertension, oxygen-dependent severe pulmonary disease;
  • Patient with a known sero-positivity for HIV (human immunodeficiency virus) or history of any other immunosuppressing disease;
  • Patient with active or chronic hepatitis B or C;
  • Patient with any active or chronic infection within four weeks before screening or between the screening and baseline visits;
  • Patient with any mycobacterial disease, patient with a positive PPD, a chest X-Ray suggestive of tuberculosis or patient taking anti-tuberculosis medication;
  • Patient with a known hypersensitivity to etanercept or one of its components or known to have antibodies to etanercept;
  • Patient who received a live attenuated vaccines within 12 weeks of Day 0 or plan to receive one during the study;
  • Current pregnancy or lactation;
  • At the investigator's discretion, patient with current or history of alcohol or drug abuse that would interfere with the ability of the patient to comply with the study protocol;
  • Patient with systemic lupus erythematosus or demyelinating disorder (optic neuritis, multiple sclerosis or other);
  • Patient with a history of cancer within five years of Day 0 or presence of cancer except for treated basal or squamous cell carcinoma and in situ cervix carcinoma;
  • Patient who failed to respond to nbUVB in the past;
  • Patient who have a contra-indication to nbUVB;
  • Patient with latex sensitivity (applicable only if they are using prefilled syringe or prefilled SureClickTM autoinjector presentations);
  • Patient with a history of non-compliance with other therapies.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640393

Locations
Canada, Manitoba
Winnipeg Clinic
Winnipeg, Manitoba, Canada, R3C 0N2
Canada, Ontario
The Guenther Dermatology Research Centre
London, Ontario, Canada, N6A 3H7
Mediprobe Research inc.
London, Ontario, Canada, N5X 2P1
Lynderm Research Inc.
Markham, Ontario, Canada, L3P 1A8
Bank on Beauty
Niagara Falls, Ontario, Canada, L2E 2R4
Sudbury Skin Clinic
Sudbury, Ontario, Canada, P3E 5M4
Canada, Quebec
Innovaderm Research Laval Inc
Laval, Quebec, Canada, H7S 2C6
Innovaderm Research Inc.
Montreal, Quebec, Canada, H2K 4L5
Clinique Dermatologique Fleury
Montreal, Quebec, Canada, H2C 1R9
Canada
Centre de Recherche Dermatologique du Quebec Metropolitain
Quebec, Canada, G1V 4X7
Sponsors and Collaborators
Innovaderm Research Inc.
Amgen
Investigators
Principal Investigator: Robert Bissonnette, MD Innovaderm Research Inc.
  More Information

No publications provided by Innovaderm Research Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Innovaderm Research Inc.
ClinicalTrials.gov Identifier: NCT00640393     History of Changes
Other Study ID Numbers: Inno-6007
Study First Received: March 18, 2008
Results First Received: August 27, 2010
Last Updated: September 1, 2011
Health Authority: Canada: Ethics Review Committee

Keywords provided by Innovaderm Research Inc.:
Etanercept, UVB, Enbrel, Psoriasis.

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014