A Prospective Open-Label Trial of Adalimumab in Progressive Sarcoidosis
18 Years
85 Years
Both
Sarcoidosis
Trial Information
A Prospective Open-Label Trial of Adalimumab in Progressive Sarcoidosis
This study consists of 11 visits (including screening).
Screening Procedures:
A chest radiograph (PA and lateral) must be obtained within 3 months prior to the first
study injection. It must indicate that subject is free of tuberculosis (TB). The chest
radiograph will also be used to confirm the stage of the disease.
Histologically proven sarcoidosis will be confirmed.
Demographic data, a complete medical history (including signs and symptoms of sarcoidosis),
a physical examination (including vital signs, weight and height). The medical history will
include questions about history of recent TB and history of close contact with persons who
might have TB. Concomitant medications, including the use of oral corticosteroids and
immunosuppressants, will be reviewed and recorded. In addition the inclusion and exclusion
criteria will be reviewed.
A tuberculin skin test will be performed.
A serum pregnancy test will be performed for all women within the 4-week period prior to the
Baseline (Week 0) Visit. All women must test negative for pregnancy at screening.
ATS dyspnea score will be assessed.
The 6-minute walk test will be performed with Borg's CR10 dyspnea score obtained before and
after.
Pulmonary function tests [PFTs] (spirometry) will be performed.
Blood samples for routine laboratory analyses will be obtained.
AE monitoring will also be performed.
Subjects who qualify for the study should be assigned to receive treatment within 14 days of
the screening visit except if additional time is required for repeat TB skin testing.
Patients should still meet all of the inclusion criteria and none of the exclusion criteria
at the time of the baseline visit before starting the injections. Subjects must agree to use
appropriate contraception.
The procedures involved at all study visits are described below.
- Informed Consent:
(Screening Visit): Subjects will be asked to review this consent form and discuss with the
study doctor or study staff any questions they may have
- Health and Medication Questions:
(Screen, Weeks 0, 2, 6, 12, 24, 30, 36, 45, 52): Subjects will be asked to answer questions
about their health, their medical history, and the medications they take.
- Physical Exam:
(Screen, Weeks 6, 24, 52): Do a physical exam.
- Vital Signs:
(Screen, Weeks 0, 6, 12, 24, 52): Blood Pressure, Pulse, Temperature
- Height and Weight:
(Screen, Week 52)
- Blood Tests:
(Screen, Weeks 12, 24, 45, 52): Approximately 3 teaspoons of blood will be drawn from a vein
in subject's hand or arm for these tests.
- Lung Function Test:
(Screen, Weeks 24, 52): Subject will be given a mouthpiece and asked to take deep breaths
into a machine connected to a computer according to the cues of a staff member. The machine
will measure the capacity of subject's lungs.
- Chest X-ray:
(Screen, Weeks 12, 24, 52):
- Tuberculosis Test:
(Screen only): Subject will be asked specific questions regarding their history of
tuberculosis (also called TB: a type of bacterial lung infection) or personal contact with
people with active tuberculosis. Subjects with active tuberculosis cannot be in the study.
Subjects will be given a skin test for tuberculosis. For all subjects in this trial, a TB
skin test with negative results must be obtained.
- 6 Minute Walk Test: (Screen, Weeks 0, 12, 24, 52): Subject will be asked to complete a
test where they will walk for 6 minutes. Subject will be asked specific questions
regarding any shortness of breath they have.
- Pregnancy Test:
(Screen only): A pregnancy blood test will be performed on all women of childbearing
potential at the screening visit. The results of the test must be negative in order for
subject to participate in the study.
- ECG:
(Week 0 only)
- Study Drug Administration:
(Weeks 0, 2, 6, 12, 18, 24, 30, 36, 45): Subject will receive study drug at the Week 0 Visit
and be taught how to give themselves injections. Subject will be given a supply of study
drug and clinical supplies that will last until the next study visit. Subject will be
required to return all unused study drug as well as the packaging for the used study drug at
each visit.
- Questionnaires:
(Weeks 0, 2, 12, 18, 24, 30, 36, 45): Prior to receiving any study drug, subject will be
asked questions about their symptoms and quality of life, including their ability to care
for themselves and carry out normal everyday activities (respiratory and health surveys) and
health questionnaires.
All subjects will return for efficacy and safety evaluations at each time point including
week 52, whether or not they complete the entire treatment schedule and whether or not they
are (still) responding to treatment.
We will watch carefully for signs and symptoms of CHF and active TB at follow-up evaluations
for all patients. The study agent will be stopped in subjects who are found to have NYHA
Class III or IV CHF, severe right-sided heart failure, cor pulmonale, and/or active TB after
enrollment in the study but they must return for further follow-up evaluations.
Inclusion Criteria:
- Men and women > 18 years of age.
- Sarcoidosis diagnosed at least 1 year prior to screening.
- Histologically proven sarcoidosis prior to screening.
- Have a diagnosis of sarcoidosis with evidence of parenchymal disease on chest
radiograph (Stage II or III) or Stage I disease by chest radiographs and evidence of
abnormal PFT as below or normal chest radiograph; or abnormal PFT, with abnormal
chest computed tomography (CT) and evidence of sarcoid lung involvement by histology.
Subjects with concurrent extrapulmonary sarcoidosis, particularly skin and eye
involvement, are encouraged to be enrolled.
- Have forced vital capacity (FVC) > 40 and < 80% of predicted.
- Have an American Thoracic Society (ATS) dyspnea score of > Grade 1.
- Have been receiving pre-study treatment that includes at least 10 mg/day prednisone
(or equivalent dose of corticosteroid) as a single agent, or 1 or more
immunosuppressant (e.g., methotrexate, azathioprine, cyclophosphamide, chloroquine,
leflunomide, hydroxychloroquine, mycophenolate mofetil, cyclosporine, tacrolimus,
corticosteroids) for at least the 3-month period immediately prior to screening.
Subjects must be on a stable dose of these medications for > 4 weeks before starting
the study medication.
- Adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine
device, barrier method with spermicide, or surgical sterilization) must be used for
the duration of the study and such precautions should be continued for 6 months after
receiving the last study agent injection.
- Are considered eligible based on TB screening
Exclusion Criteria:
- Have used any investigational drug within 1 month prior to screening.
- Have received previous administration of a treatment with any other therapeutic agent
targeted at reducing tumor necrosis factor [TNF] (e.g., pentoxifylline, thalidomide,
etanercept, infliximab) within 3 months prior to screening.
- Have received previous administration of adalimumab.
- Have received any live virus or bacterial vaccinations within the 3 months before
the first dose of the study agent or are expected to receive any live virus or
bacterial vaccinations during the trial or up to 3 months after the last dose of the
study agent.
- Have had any previous adverse reactions or allergic reactions (e.g., anaphylaxis)
associated with the administration of monoclonal antibodies.
- Have New York Heart Association (NYHA) Class III or IV congestive heart failure
(CHF).
- Have a history of severe right-sided heart failure or cor pulmonale.
- Have had serious infections within 2 months of screening. Less serious infections
(such as acute upper respiratory tract infection [colds] or a simple urinary tract
infection) need not be considered as exclusion at the discretion of the investigator.
- Are considered ineligible according to the United States of America (USA)-specific TB
screening.
- Have or have had an opportunistic infection (e.g., herpes zoster [shingles],
cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma,
histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
- Have a known infection with human immunodeficiency virus (HIV).
- Have current signs and symptoms of systemic lupus erythematosus, or severe,
progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary,
cardiac, neurologic, or cerebral diseases (with the exception of sarcoidosis).
- Presence of a transplanted organ (with the exception of a corneal transplant) > 3
months prior to screening.
- Have any known malignancy or history of malignancy within 5 years prior to screening.
- Have a history of lymphoproliferative disease including lymphoma, or signs and
symptoms suggestive of possible lymphoproliferative disease.
- Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or
within the 6-month period thereafter.
- Have had a known substance abuse or dependency, drug or alcohol within 3 years of
screening.
- Have poor tolerability of subcutaneous injection or lack of adequate venous access
for required blood sampling.
- Have a known history of demyelinating disease such as multiple sclerosis or optic
neuritis.
- Presence of a non-sarcoidosis condition affecting survival.
- Have mental health problems interfering with participation.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
The primary objective of this study is to evaluate the efficacy and safety of adalimumab, as measured by pulmonary function, in subjects with chronic sarcoidosis with pulmonary involvement who are symptomatic despite current treatment.
Outcome Time Frame:
24 Weeks
Safety Issue:
No
Principal Investigator
Nadera J. Sweiss, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
The University of Chicago Hospitals
Authority:
United States: Food and Drug Administration
Study ID:
14093A
NCT ID:
NCT00311246
Start Date:
April 2006
Completion Date:
September 2008
Related Keywords:
- Sarcoidosis
- Sarcoidosis
- Humira
- Adalimumab
- Tumor Necrosis Factor Inhibitors
- Sarcoidosis
Name | Location |
|---|---|
| The University of Chicago | Chicago, Illinois 60637 |
