A Study of Adalimumab to Treat Sarcoidosis of the Skin

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00274352
• Date of registration: 06/01/2006
• Prospective Registration: Yes
• Primary sponsor: Pariser, Robert J., M.D.
• Public title: A Study of Adalimumab to Treat Sarcoidosis of the Skin
• Scientific title: A Double-Blind, Randomized, Placebo-Controlled Study of Adalimumab in the Treatment of Cutaneous Sarcoidosis
• Date of first enrolment: September 2006
• Target sample size: 16
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00274352
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Robert J Pariser, MD
• Affiliation: Eastern Virginia Medical School

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Subject is > 18 years of age.

2. Subject must have moderate to severe cutaneous sarcoidosis with chronic indurated
lesions (papules, nodules, and/or plaques), which histopathologically show
non-caseating granulomas with negative special stains for microorganisms (AFB and PAS
or GMS). Accepted clinical variants include, but are not necessarily limited to the
following:

- lupus pernio

- nodular

- subcutaneous

- annular

- angiolupoid

- plaque

- papular

- lichenoid

- psoriasiform

3. For purposes of this study "moderate to severe cutaneous sarcoidosis" is defined as
the presence of sarcoidal skin lesions with any of the following features:

- At least 5 easily visible facial lesions, or

- Disease which involves > 3% BSA, or

- Disease which confers functional impairment (e.g. nasal or visual field
obstruction), or

- Disease which confers significant symptoms of itching and/or pain.

4. If 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 using one of the following methods of birth
control for the duration of the study and 90 days after study completion:

- condoms, sponge, foams, jellies, diaphragm, or intrauterine device

- contraceptives (oral or parenteral) for three months prior to study drug
administration

- a vasectomized sole partner

5. Females of childbearing potential must have a negative serum pregnancy test at
screening visit.

6. Subject must have no history of nor evidence of tuberculosis, either active or
previously treated. This determination will be based on a negative PPD skin test and
negative chest radiograph at screening, negative history of previous tuberculosis,
and negative history of previous exposure to tuberculosis.

7. Subject must be willing and able to give informed consent and to comply with the
requirements of the protocol.

8. Subject must be willing and able to self-administer SC injections or to have a
qualified person available to administer SC injections.

9. The following criteria for concomitant treatments of sarcoidosis must be met:

- Topical therapies (corticosteroids) must be discontinued at least 2 weeks prior
to baseline visit.

- Intralesional therapies (corticosteroids) must be discontinued at least 4 weeks
prior to baseline visit.

- Systemic therapies (MTX, antimalarials, prednisone, immunosuppressants,
thalidomide, tetracycline derivatives) must be discontinued at least 4 weeks
prior to baseline visit.

OR if a subject is on such topical or oral medications, the dose has been stable for these
same time intervals and is likely to remain stable for the duration of the study.
Patients whose non-cutaneous disease is being managed by other physicians will continue to
have their care directed by these physicians. The managing physicians will be kept
informed of the patients' status, consistent with study blinding. If the patient's dose
of a concomitant systemic therapy for non-cutaneous sarcoidosis must change by more than
20% of the dose at study entry due to a change in medical condition during the
double-blind phase, the subject will be discontinued from the study. During the
open-label phase the need for a greater than 20% increase in dose of concomitant treatment
for non-cutaneous sarcoidosis will be viewed as treatment failure and the patient will be
discontinued from the study. Reduction of the dose of such treatment of any magnitude
will not result in discontinuance. Continued use of intralesional therapies is not
permitted. Inhaled corticosteroids for a stable medical condition are allowed.

Exclusion Criteria:

1. Evidence of other active skin diseases or skin infections during screening that may
interfere with evaluation of sarcoidosis.

2. Subject has a known sensitivity to any component of the study medication. (See Table
4.)

3. Subject has an active infection requiring systemic antibiotics at time of screening.

4. Subject has a history of malignancy or lymphoproliferative disease within the past 5
years, excluding successfully treated non-melanoma epithelial skin cancer and/or
localized carcinoma in situ of the cervix.

5. Subject has a history of congestive heart failure.

6. Subject has a poorly controlled medical condition including, but not limited to,
unstable cardiovascular disease, poorly controlled diabetes, recent stroke, history
of recurrent infections, or any other condition for which, in the opinion of the
investigator, participation in the study would place the subject at risk.

7. Subject has a history of demyelinating CNS disease.

8. Subject has a history of listeriosis, treated or untreated tuberculosis, exposure to
individuals with tuberculosis, persistent or active infections requiring
hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV
antifungals within 30 days of baseline, OR oral antibiotics, antivirals, or
antifungals for purpose of treating infection, within 14 days of baseline.

9. Subject is currently using or plans to use antiretroviral therapy at any time prior
to or during study.

10. Previous use of anti-TNF agent(s).

11. Receipt of any other investigational product within 30 days prior to the first dose
of investigational product.

12. Subject is known to have immune deficiency or is immunocompromised.

13. Female subjects who are pregnant, breast feeding, or are considering becoming
pregnant during the study or within 150 days of the last dose of study medication.

14. Subject has a history of clinically significant drug or alcohol abuse in the last
year.

15. Subject is considered by the investigator, for any reason, to be an unsuitable
candidate for study participation.

16. Clinically significant ECG abnormalities at screening visit.

17. Hgb < 8.5 g/dL in females and < 9.0 in males.

18. WBC count < 3000/mm2

19. AST or ALT > 2.0 times the upper limit of normal for the age range, confirmed by a
repeat measure.

20. Bilirubin > 3mg/dL

21. Creatinine > 1.6 mg/dL in women, and > 1.8 mg/dL in men.

22. Subject plans to receive any


Age minimum: 18 Years
Age maximum: 89 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Sarcoidosis

Intervention(s)

Drug: adalimumab

Primary Outcome(s)

The proportion of subjects who are Responders, achieving at least Moderate Improvement on the Physician's Global Assessment, after 12 weeks of treatment during Period A (double-blind phase). [Time Frame: at completion of double-blind phase (12 weeks)]

Secondary Outcome(s)

Proportion of subjects with observed improvement on chest radiograph after 12 weeks of treatment during Period A. [Time Frame: at completion of double-blind phase (12 weeks)]

Change in the patient's Quality of Life score relative to baseline after 12 weeks of treatment during Period A. [Time Frame: at completion of double-blind phase (12 weeks)]

Proportion of subjects with improvement in pulmonary diffusing capacity after 12 weeks of treatment during Period A. [Time Frame: at completion of double-blind phase (12 weeks)]

Proportion of subjects achieving a PGA (Physician's Global Assessment) of Clear or Marked Improvement after 12 weeks of treatment during Period A. [Time Frame: at completion of double-blind phase (12 weeks)]

(Sub group analysis of all subjects by CXR stage at study entry will be performed for all respiratory variables) [Time Frame: at completion of double-blind phase (12 weeks)]

Change in the Patient's Global Assessment relative to baseline after 12 weeks of treatment during Period A. [Time Frame: at completion of double-blind phase (12 weeks)]

Change target lesion dimensions and estimated thickness. [Time Frame: at completion of double-blind phase (12 weeks)]

Proportion of subjects achieving at least a PGA of Mild Improvement after 12 weeks of treatment during Period A. [Time Frame: at completion of double-blind phase (12 weeks)]

Proportion of subjects with a 12% or greater improvement (minimum of 200mL change) in FVC and/or FEV1 after 12 weeks of treatment during Period A. (This is the minimum change thought to be clinically significant per American Thoracic Society Statement [Time Frame: at completion of double-blind phase (12 weeks)]

Secondary ID(s)

HUM05-006

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Abbott

Virginia Clinical Research, Inc.