Clinical trial NCT01181570: Efficacy and Safety of Adalimumab in Patients With Psoriasis and Obstructive Sleep Apnea
Official title: Efficacy and Safety of Adalimumab in Patients With Psoriasis and Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psoriasis
Sleep Apnea, Obstructive
Keywords: psoriasis
adalimumab
obstructive sleep apnea
obesity
Lead sponsor: Innovaderm Research Inc.
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2010-08-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the effect and safety of adalimumab in approximately 20 subjects with mild to moderate psoriasis and sleep apnea and will be conducted in one treatment center located in Montreal.

Patients with psoriasis often have additional disorders such as obesity. Obese patients are more at risk of developing obstructive sleep apnea. This is believed to be caused by both the collapse of upper airways and inflammation (swelling). Adalimumab, a drug currently approved by Health Canada for the treatment of psoriasis, blocks tumor necrosis factor-alpha (TNF-alpha). This chemical is present at higher levels in patients with sleep apnea. It is believed that adalimumab could improve obstructive sleep apnea by lowering the levels of TNF-alpha.


Eligibility criteria: Inclusion Criteria:

* Men or women are 18 to 80 years of age at time of consent.
* Has at least a 6-month history of chronic moderate to severe psoriasis and is a candidate for systemic therapy.
* Has a body surface area (BSA) covered with psoriasis of at least 5% or more at Day 0.
* Has a diagnosis of obstructive sleep apnea confirmed by at least 15 episodes/hour of apnea/hypopnea at the polysomnographic testing on Day -2.
* Unless surgically sterile (or at least 1 year post-menopausal), or abstinent, patient (female) is willing to use an effective method of contraception for at least 30 (90 for "c") days before Day 0 and until at least 6 months after the last drug administration. Effective method of contraception are:

  * Condom with spermicidal foam, cream or gel, sponge with spermicidal foam, cream or gel, diaphragm with spermicidal foam, cream or gel
  * Intra uterine device (IUD)
  * Contraceptives (oral or parenteral)
  * Nuvaring
  * Vasectomised partner
  * Same-sex partner
* Negative serum pregnancy test at the screening visit for female patient of childbearing potential only.
* Patient 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 performed at screening.
* Patient will be evaluated for latent tuberculosis (TB) infection with a purified protein derivative (PPD) or a QuantiFERON-TB Gold test and Chest X-Ray (CXR). All patients who previously received TB immunization (BCG vaccination) will have the QuantiFERON-TB Gold test performed. Patient who demonstrates evidence of latent TB infection (either PPD more than or equal to 5 mm of induration or positive QuantiFERON-TB Gold) or suspicious CXR will not be allowed to participate.
* Capable of giving informed consent and the consent must be obtained prior to any study related procedures.
* Patient must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

Exclusion Criteria:

* Has received medical treatment for sleep apnea in the 6 months preceding Day 0.
* Presence of other skin diseases or skin infections (bacterial, fungal or viral) that may interfere with evaluation of psoriasis or with patient's safety.
* Has a history of an allergic reaction or significant sensitivity to constituents of study drug, including latex (a component of the pre-filled syringe).
* Use of any non-biological systemic therapy for the treatment of psoriasis (including PUVA (psoralen and ultraviolet A)) less than 30 days before Day 0.
* Use of investigational chemical agents within 30 days or five half-lives prior to Day 0, whichever is longer.
* Use of any biological therapy for the treatment of psoriasis less than 90 days before Day 0.
* Current use of oral or injectable corticosteroids or during the study. Inhaled corticosteroids for stable medical conditions are allowed.
* Use of any topical treatments for psoriasis or phototherapy within two weeks prior to Day 0, at the exception of low strength (hydrocortisone and desonide) topical corticosteroid for the face, groin (including genitals) and inframammary areas.
* Has received Anakinra/Kineret within the last 2 weeks prior to Day 0 or is likely to receive Anakinra/Kinaret during the course of the study.
* Has a poorly controlled medical condition, such as uncontrolled diabetes, documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent stroke (within the past 90 days), chronic leg ulcer or any other condition which, in the opinion of the investigator, would put the patient at risk if participating in the study.
* Has a history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. optic neuritis, visual disturbance, gait disorder/ataxia, facial paresis, apraxia).
* Has a 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.
* 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 Day 0.
* Has received any live attenuated vaccine 28 days or less before Day 0 or plans to receive one during the study.
* Has hepatitis B or hepatitis C viral infection.
* Has any of the following: hemoglobin ≤ 10 g/L, white blood cell count ≤ 3.0 X 10\^9/L, platelet count ≤130 X 10\^9/L, ALT ≥ 3 times the upper limit of normal, AST ≥ 3 times the upper normal limit, total bilirubin ≥ 2 times the upper normal limit or creatinine ≥ 150 µmol/L.
* Current use or plan to use anti-retroviral therapy at any time during the study.
* Is known to have 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.
* Has a 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.

Primary outcomes:
measure: Number of sleep apnea per hour.
timeFrame: 56 Days
Secondary outcomes:
measure: Sleep maintenance efficiency
timeFrame: 56 days
measure: Total wake time
timeFrame: 56 days
measure: Percentage of sleep time
timeFrame: 56 days
measure: Time spent in REM (rapid eye movement) stage.
timeFrame: 56 days
measure: Time spent in sleep stage N1
timeFrame: 56 days
measure: Time spent in sleep stage N3
timeFrame: 56 days
measure: REM (rapid eye movement) latency time
timeFrame: 56 days
measure: Minimum overnight oxygen saturation index
timeFrame: 56 days
measure: Oxygen desaturation index
timeFrame: 56 days
measure: Sleep related quality of life questionnaire (FOSQ)
timeFrame: 56 days
measure: Epworth sleepiness scale
timeFrame: 56 days
measure: Daytime sleep latency
timeFrame: 56 days
measure: Safety of adalimumab
timeFrame: 56 weeks
measure: Body surface area (BSA)
timeFrame: 56 days
measure: Physician's Global Assessment (PGA)
timeFrame: 56 days
measure: Psoriatic Area and Severity Index (PASI)
timeFrame: 56 days
measure: PASI 75 (75% reduction in Psoriatic Area and Severity Index)
timeFrame: 56 days
measure: Proportion with PGA (Physician's Global Assessment) of 0 or 1
timeFrame: 56 days
measure: Time to sleep induction
timeFrame: 56 days
measure: Time spent in sleep stages N2
timeFrame: 56 days
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Innovaderm Research Inc.
state: Quebec
Study officials:
affiliation: Innovaderm Research Inc.
name: Robert Bissonnette, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: