Adalimumab-psoriasis and Small Bowel Lesions

Open-label Study on Small Bowel Lesions Suggestive of Crohn's Disease in Patients With Moderate to Severe Plaque Psoriasis Treated With Adalimumab

This study will determine the prevalence of small bowel lesions suggestive of Crohn's disease (CD) in patients with moderate to severe plaque psoriasis using capsule endoscopy. The study also aims to determine if the treatment of psoriasis with adalimumab will have an effect on the healing of the small bowel for patients who have lesions suggestive of CD.

Patients with psoriasis are at increased risk of developing Crohn's disease (CD), but the exact prevalence of CD in patients with psoriasis at this time is unknown as many patients probably have undiagnosed disease as the early signs will often cause no symptoms. CD is therefore receiving very little attention from dermatologists who are treating patients with psoriasis. For example, very few dermatologists will actively question patients with psoriasis about symptoms of CD. This lack of knowledge may induce delays in diagnosis. By the time the diagnosis is made and patients receive their first treatment, they may already have significant fibrosis and stenosis of the intestine. Current treatments, including adalimumab, cannot reverse small bowel anomalies to normal in the presence of fibrosis. Therefore, many patients with a late diagnosis will still have symptoms or will eventually require surgery despite good control of the inflammation. Treatment of CD should start as early as possible, as early treatment has been associated with an increased rate of complete healing. Complete control of the disease at its early stages may prevent complications.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis; Crohn's Disease
• Intervention / Treatment: Drug: Adalimumab; Device: Capsule endoscopy

Detailed Description

This open-label, phase IV, 24-week study will recruit a total of 100 patients with moderate to severe plaque psoriasis without a diagnosis of inflammatory bowel disease. All patients will undergo capsule endoscopy at the beginning of the study to detect the presence of small bowel lesions suggestive of CD such as erosions and ulcers. All patients will receive adalimumab 80 mg followed by 40 mg at week 1 and 40 mg every other week (EOW) thereafter. Patients for whom no small bowel lesions suggestive of CD were detected will remain in the study and under adalimumab therapy until week 12. A second capsule endoscopy will be performed 24 weeks after initiation of adalimumab for patients who had small bowel lesions suggestive of CD to evaluate changes in bowel inflammation.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Markham, Ontario, Canada, L3P 1A8
      • Lynderm Research
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research Inc.
    • St-Hyacinthe, Quebec, Canada, J2S 6L6
      • Dr Isabelle Delorme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women are 18 to 80 years of age at time of consent
• At least a 6-month history of chronic moderate to severe plaque psoriasis and is a candidate for systemic therapy
• BSA covered with psoriasis of at least 5% or more at Day 0
• Unless subject or subject's partner is in a menopausal state for at least a year, surgically sterile, clinically diagnosed infertile, having a same-sex partner or abstinent, female of childbearing potential or male patient (or his partner) is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 6 months after the last study drug administration
• Is judged not to have contraindications to adalimumab as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination and chest X ray (CXR) performed at screening
• Negative results for latent TB infection with a PPD or QuantiFERON®-TB Gold test and a CXR
• Capable of giving informed consent and the consent must be obtained prior to any study related procedures
• Must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections

Exclusion Criteria:

• Diagnosis of inflammatory bowel's disease
• Presence of any evidence of gastrointestinal obstruction, strictures and/or fistulas
• Presence of highly suspected or documented gastroparesis
• Known presence of gastrointestinal motility disorders
• Known presence of delayed gastric emptying
• Prior abdominal surgery of the gastrointestinal tract other than uncomplicated procedures that would be unlikely to lead to bowel obstruction based on the clinical judgment of the investigator
• Presence of pacemaker, defibrillator or other electromedical device
• Expected to undergo a MRI examination within 7 days after ingestion of the capsule
• Swallowing disorder
• Presence of other skin diseases or skin infections that may interfere with evaluation of psoriasis or with patient's safety at Day 0
• History of an allergic reaction or significant sensitivity to constituents of study drug, including latex
• Use of any biological therapy for the treatment of psoriasis less than 90 days before Day 0
• Use of any other non-biological systemic therapy for the treatment of psoriasis within 28 days before Day 0
• Is planning to intentionally increase exposure to ultraviolet light at any time during the study period
• Is taking or requires systemic (i.e., oral or injectable) corticosteroids within 28 days of Day 0 or during the study
• Used any topical treatments for psoriasis or phototherapy within two weeks prior to Day 0
• Received Anakinra/Kineret within the last 2 weeks prior to Day 0
• Used any investigational non-biological agent within 30 days prior to Day 0, or within 5 half lives of the investigational agent prior to day 0
• Used NSAIDs for 28 days before Day 0
• Has a poorly controlled medical condition in the opinion of the investigator, would put the patient at risk if participating in the study
• Multiple sclerosis or presents with or has a history of neurologic symptoms suggestive of CNS demyelinating disease
• Current signs or symptoms of or a history of systemic lupus erythematosus or lupus like syndrome
• 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
• 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 Day 0
• Received any live attenuated vaccine 28 days or less before Day 0 or plans to receive one during the study
• Hepatitis B or hepatitis C
• Clinically significant abnormal results for hemoglobin, white blood cell count, platelet count, ALT, AST, total bilirubin or creatinine
• Current use or plan to use anti-retroviral therapy at any time during the study
• Known immune deficiency or is immunocompromised
• Current pregnancy or lactation or considering becoming pregnant during the study or for 150 days after the last dose of study medication
• History of clinically significant drug or alcohol abuse in the last year
• Is considered by the investigator, for any reason, to be an unsuitable candidate for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: adalimumab; All patients will receive adalimumab 80 mg followed by 40 mg at week 1 and 40 mg every other week (EOW) thereafter.

Drug: Adalimumab; Adalimumab will be administered sub-cutaneously to all patients entering the study with a loading dose of 80 mg followed by 40 mg at week 1 and 40 mg every other week. Patients who did not have small bowel lesions detected will be in the study and receive adalimumab until week 12. Patients who had small bowel lesions detected will be in the study and receive adalimumab until week 24.; Other Names: Humira; Device: Capsule endoscopy; All patients will undergo capsule endoscopy (EndoCapsule EC type 1; Olympus) to treatment initiation (adalimumab) in order to detect the presence of small bowel lesions suggestive of Crohn's disease. Twenty-four (24) weeks after treatment with adalimumab was initiated, patients for whom small bowel lesions were detected will undergo a second capsule endoscopy to evaluate changes in bowel inflammation.; Other Names: EndoCapsule EC-1; OLYMPUS EC TYPE 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prevalence of small bowel lesions suggestive of Crohn's disease in patients with moderate to severe plaque psoriasis as visualized by capsule endoscopy	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction of mucosal healing at week 24 after initiation of adalimumab in patients with small bowel lesions suggestive of Crohn's disease and psoriasis as defined by absence of villous edema, erosions and ulcers		24 weeks
Study the relationship between mucosal healing and plaque psoriasis improvement in patients with small bowel lesions suggestive of Crohn's disease and psoriasis	as evaluated by the absence of villous edema, erosions and ulcers and mean change from baseline in PASI at week 24	24 weeks
Study the relationship between levels of fecal calprotectin and endoscopy findings		Day 0 and week 24
Change from baseline in PASI at Week 12 for patients who had presence of small bowel lesions suggestive of CD as compared to patients who did not have small bowel lesions suggestive of CD		12 weeks
Proportion of patients reaching Psoriasis Area and Severity Index (PASI) 75 at Week 12 for patients who had small bowel lesions suggestive of CD as compared to patients who did not have small bowel lesions suggestive of CD.		12 weeks

Collaborators and Investigators

• Sponsor: Innovaderm Research Inc.
• Collaborators: Abbott

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): April 1, 2016

Study Registration Dates

• First Submitted: March 15, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (ESTIMATE): March 16, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: adalimumab; Crohn's Disease; Plaque psoriasis; capsule endoscopy; small bowel lesions
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Skin Diseases, Papulosquamous; Inflammatory Bowel Diseases; Psoriasis; Crohn Disease; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: Inno-6021; IMM-11-0110 (OTHER_GRANT: Abbott)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO