Clinical trial NCT01199887: Trial Of IW001 in Patients With Idiopathic Pulmonary Fibrosis
Official title: A Phase One, Open Label, Multi-Dose Study to Evaluate the Safety, Tolerability, and Biologic Effects of Three Doses of IW001 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: safety, biologic effects, IPF, autoimmune
Lead sponsor: ImmuneWorks
Sponsor class: INDUSTRY
First posted: 2010-09-13
Enrollment: 30
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, Phase One, multicenter study, designed to evaluate the safety, tolerability, to explore the biologic effects, and to explore the clinical effects of the following doses of IW001: 0.1mg/day, 0.5 mg/day, and 1.0 mg/day, when administered once a day orally for 24 weeks in patients with IPF.

Detailed description: IW001 is a therapeutic designed to treat anti-Col (V)-mediated autoimmune diseases via oral tolerance. With the identification of the specific antigen involved in the autoimmune disease process in IPF, IW001 induced oral tolerance may be an effective treatment. IW001 is taken orally, introduced into the mucosal immune system at the Peyer's Patches in the distal small intestine, where antigen-presenting cells present the antigen to regulatory T cells (Tregs). These antigen-specific Tregs enter the blood stream and traffic to areas where the specific antigen has generated an autoimmune response. Thus, IW001 may produce selective suppression of immune responses against Col (V).

Eligibility criteria: Inclusion Criteria:

* Patients must meet all of the following to be included in the study:

  1. Diagnosis of IPF (ATS criteria) prior to the Baseline visit.
  2. Forced Vital Capacity (FVC) ≥ 50% of predicted.
  3. Lung Diffusion Capacity (DLCO) ≥ 35% of predicted.
  4. Ages 35-75 years inclusive.
  5. Positive for anti-Col (V) antibodies.
  6. White blood cell count (WBC) ≥ 2500 mm3.
  7. Hematocrit ≥ 25% and ≤ 59%.
  8. Platelets ≥ 100,000 mm3.
  9. Creatinine ≤ 1.5x Upper Limits of Normal (ULN).
  10. Bilirubin ≤ 1.5x ULN.
  11. Aspartate aminotransferase (AST, SGOT) ≤ 1.5x ULN.
  12. Females of child-bearing potential (defined as less than one year post-menopausal or not surgically sterile) must be using an acceptable method of birth control or practicing abstinence from the time consent is signed until 30 days after treatment discontinuation. If sexually active, female patients must use a double barrier method of birth control, such as a condom and spermicidal. Patient must have a negative pregnancy test at the Screening and Baseline visits.
  13. Willing and able to provide adequate written informed consent.

      Exclusion Criteria:
* Patients will be excluded from the study for any of the following:

  1. Concurrent use of systemic corticosteroids or immunosuppressives within 30 days of the Baseline visit.
  2. Chronic NSAID use (limited, i.e., up to 72 hours continuous use of NSAIDs will be permitted during the study), (see Section 9, concomitant medications).
  3. N-acetyl cysteine (NAC) use within 14 days of the Baseline visit.
  4. Any disease, condition or surgery (e.g. inflammatory bowel disease, surgical resection) that may cause malabsorption of IW001.
  5. Known or suspected allergy to bovine products.
  6. Concurrent or prior use of any experimental medication within 30 days of the Baseline visit.
  7. History of smoking within three months prior to the Baseline visit.
  8. Known Hepatitis C or Human Immunodeficiency Virus (HIV) infections.
  9. Evidence of active infection at the Baseline visit.
  10. History of unstable or deteriorating cardiac disease.
  11. Myocardial infarction, coronary artery bypass, or angioplasty within 6 months of the Baseline visit.
  12. Unstable angina pectoris or congestive heart failure requiring hospitalization within 6 months of the Baseline visit.
  13. Uncontrolled arrhythmia.
  14. Patient has a history of illicit drug or alcohol abuse in the past year or current evidence of such abuse or addiction in the opinion of the Investigator.
  15. Patient has positive findings on urine drug screen.
  16. Any other clinically significant illness, that, in the opinion of the Investigator, might put the patient at risk of harm during the study or might adversely affect the interpretation of the study data.
  17. Females who are pregnant and/or lactating.

Primary outcomes:
measure: To evaluate the safety and tolerability of three doses of IW001 (0.1 mg/day, 0.5 mg/day, and 1.0 mg/day orally) in patients with IPF patients over a 24 week treatment period.
timeFrame: Monthly during the 24 week treatment period.
Secondary outcomes:
measure: To explore the biologic effects of IW001 on T-cell and B-cell reactivity. To explore relationships between Col V reactivity and clinical measures of lung function in patients with IPF.
timeFrame: Monthly during the 24 week treatment period.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: IUPUI
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Newark
country: United States
facility: Newark Beth Israel Hospital
state: New Jersey
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
Study officials:
affiliation: ImmuneWorks, Medical Consultant
name: Terrence Chew, MD
role: STUDY_DIRECTOR
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