Trial Outcomes & Findings for Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (NCT NCT01969409)
NCT ID: NCT01969409
Last Updated: 2024-08-21
Results Overview
Titers of anti-HEp-2 autoantibodies, by indirect immunofluorescence assays (IFA) over 9 months, month 9 reported. Titers represent the highest dilution of patient plasma wherein the autoantibodies can be detected. Higher titers denote greater autoantibody concentrations.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
baseline to 9 months
Results posted on
2024-08-21
Participant Flow
Participant milestones
| Measure |
Placebo
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Overall Study
STARTED
|
28
|
30
|
|
Overall Study
COMPLETED
|
25
|
26
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Placebo
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Overall Study
Death
|
2
|
2
|
|
Overall Study
Transplant
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis
Baseline characteristics by cohort
| Measure |
Placebo
n=28 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=30 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70 years
STANDARD_DEVIATION 7 • n=5 Participants
|
68 years
STANDARD_DEVIATION 7 • n=7 Participants
|
69 years
STANDARD_DEVIATION 7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
30 participants
n=7 Participants
|
58 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to 9 monthsPopulation: 7 not analyzed: 4 deaths, 2 transplants, 1 dropout
Titers of anti-HEp-2 autoantibodies, by indirect immunofluorescence assays (IFA) over 9 months, month 9 reported. Titers represent the highest dilution of patient plasma wherein the autoantibodies can be detected. Higher titers denote greater autoantibody concentrations.
Outcome measures
| Measure |
Placebo
n=25 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=26 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Autoantibodies to Human Epidermoid (HEp)-2 Cells
|
288 titer
Standard Error 63
|
177 titer
Standard Error 29
|
SECONDARY outcome
Timeframe: baseline to 9 monthsPopulation: 7 not analyzed: 4 deaths, 2 transplants, 1 dropout
Changes of anti-HSP70 plasma concentrations as determined by ELISA, month 9 reported. The result is expressed as optical density (OD) units. The greater the number; the more autoantibody.
Outcome measures
| Measure |
Placebo
n=25 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=26 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Changes in Anti-Heat Shock Protein 70 (HSP70) Autoantibodies
|
1.0 OD units
Standard Error 0.13
|
0.83 OD units
Standard Error 0.08
|
SECONDARY outcome
Timeframe: baseline thru 9 monthsPopulation: 7 not analyzed: 4 deaths, 2 transplants, 1 dropout
FVC values over the observation period will be measured by spirometry, month 9 reported.
Outcome measures
| Measure |
Placebo
n=25 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=26 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Changes in Forced Vital Capacity (FVC)
|
2.6 liters
Standard Error 0.14
|
2.5 liters
Standard Error 0.16
|
SECONDARY outcome
Timeframe: during the 9 months of observationPopulation: Data not complete in 7 due to 4 deaths, 2 transplants, 1 dropout
AE in the two treatment arms will be compared. Serious adverse events, as defined by national toxicity scale.
Outcome measures
| Measure |
Placebo
n=25 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=26 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Number of Adverse Events (AE)
|
7 serious adverse events
|
12 serious adverse events
|
SECONDARY outcome
Timeframe: during the study duration of 9 monthsPopulation: Data from 7 incomplete: 4 deaths, 2 transplants, 1 dropout
The number of acute exacerbations, defined using consensus criteria (new/worsened hypoxemia and dyspnea, with characteristic radiographic changes within the last 30 days).
Outcome measures
| Measure |
Placebo
n=25 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=26 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Number of Acute Exacerbations
|
1 acute exacerbations
|
2 acute exacerbations
|
SECONDARY outcome
Timeframe: during 9 months of observationPopulation: 1 dropout (censored event)
Absolute survival in the two arms calculated by actuarial methods (Kaplan-Meier). These result in percent survival denoted as means and +/- standard error (these are detailed in the outcome table below).
Outcome measures
| Measure |
Placebo
n=28 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=30 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Absolute Survival Percentage
|
93 percent of participants
Standard Error 5
|
93 percent of participants
Standard Error 5
|
SECONDARY outcome
Timeframe: during 9 months of observationPopulation: 1 dropout
Actuarial transplant-free survival in the two arms, calculated by actuarial methods (Kaplan-Meier). These result in percent survival denoted as means and +/- standard error (these are detailed in the outcome table below).
Outcome measures
| Measure |
Placebo
n=28 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=29 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Transplant-Free Survival
|
89 percentage of participants
Standard Error 6
|
90 percentage of participants
Standard Error 6
|
SECONDARY outcome
Timeframe: during 9 months of observationPopulation: incomplete data on 1 dropout
The number of hospitalizations in the two arms will be compared.
Outcome measures
| Measure |
Placebo
n=28 Participants
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=30 Participants
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Hospitalizations
|
6 number of admissions
|
12 number of admissions
|
Adverse Events
Placebo
Serious events: 5 serious events
Other events: 21 other events
Deaths: 2 deaths
Rituximab
Serious events: 9 serious events
Other events: 24 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Placebo
n=28 participants at risk
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=30 participants at risk
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Infection
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
3.3%
1/30 • Number of events 1 • Baseline to 9 months
|
|
Gastrointestinal disorders
Infection
|
0.00%
0/28 • Baseline to 9 months
|
6.7%
2/30 • Number of events 2 • Baseline to 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Worsening respiratory function
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
6.7%
2/30 • Number of events 4 • Baseline to 9 months
|
|
Nervous system disorders
cerebral vascular accident
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Nervous system disorders
syncope
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute exacerbation of idiopathic pulmonary fibrosis
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
6.7%
2/30 • Number of events 2 • Baseline to 9 months
|
|
Cardiac disorders
Myocardial Infarct
|
0.00%
0/28 • Baseline to 9 months
|
6.7%
2/30 • Number of events 2 • Baseline to 9 months
|
|
Cardiac disorders
Right ventricular failure
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Nervous system disorders
carotid revascularization
|
0.00%
0/28 • Baseline to 9 months
|
3.3%
1/30 • Number of events 1 • Baseline to 9 months
|
Other adverse events
| Measure |
Placebo
n=28 participants at risk
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
Placebo: Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
|
Rituximab
n=30 participants at risk
Rituximab i.v. given on two occasions, with 14 days between doses.
Rituximab: i.v. rituximab given on two occasions 14 days apart.
|
|---|---|---|
|
General disorders
flushing
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
6.7%
2/30 • Number of events 3 • Baseline to 9 months
|
|
General disorders
fever
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
6.7%
2/30 • Number of events 3 • Baseline to 9 months
|
|
General disorders
dry mouth
|
14.3%
4/28 • Number of events 7 • Baseline to 9 months
|
10.0%
3/30 • Number of events 6 • Baseline to 9 months
|
|
Infections and infestations
Infection unspecified (mild)
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Cardiac disorders
chest tightness
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Cardiac disorders
arrhythmia
|
10.7%
3/28 • Number of events 3 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Cardiac disorders
Hypertension
|
7.1%
2/28 • Number of events 3 • Baseline to 9 months
|
6.7%
2/30 • Number of events 5 • Baseline to 9 months
|
|
Cardiac disorders
palpitations
|
0.00%
0/28 • Baseline to 9 months
|
6.7%
2/30 • Number of events 2 • Baseline to 9 months
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
7.1%
2/28 • Number of events 5 • Baseline to 9 months
|
10.0%
3/30 • Number of events 3 • Baseline to 9 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.6%
1/28 • Number of events 2 • Baseline to 9 months
|
23.3%
7/30 • Number of events 7 • Baseline to 9 months
|
|
Surgical and medical procedures
Brusing
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
3.3%
1/30 • Number of events 1 • Baseline to 9 months
|
|
Gastrointestinal disorders
abdominal pain
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
6.7%
2/30 • Number of events 3 • Baseline to 9 months
|
|
Gastrointestinal disorders
Anorexia
|
7.1%
2/28 • Number of events 3 • Baseline to 9 months
|
10.0%
3/30 • Number of events 3 • Baseline to 9 months
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
4/28 • Number of events 7 • Baseline to 9 months
|
16.7%
5/30 • Number of events 5 • Baseline to 9 months
|
|
Gastrointestinal disorders
Nausea
|
14.3%
4/28 • Number of events 5 • Baseline to 9 months
|
20.0%
6/30 • Number of events 7 • Baseline to 9 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.1%
2/28 • Number of events 3 • Baseline to 9 months
|
6.7%
2/30 • Number of events 2 • Baseline to 9 months
|
|
Nervous system disorders
Anxiety
|
7.1%
2/28 • Number of events 3 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Nervous system disorders
Dizzyness
|
10.7%
3/28 • Number of events 8 • Baseline to 9 months
|
6.7%
2/30 • Number of events 3 • Baseline to 9 months
|
|
Nervous system disorders
Fatigue
|
14.3%
4/28 • Number of events 7 • Baseline to 9 months
|
10.0%
3/30 • Number of events 6 • Baseline to 9 months
|
|
Nervous system disorders
Headache
|
10.7%
3/28 • Number of events 4 • Baseline to 9 months
|
16.7%
5/30 • Number of events 9 • Baseline to 9 months
|
|
Nervous system disorders
Insomnia
|
14.3%
4/28 • Number of events 5 • Baseline to 9 months
|
16.7%
5/30 • Number of events 5 • Baseline to 9 months
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
25.0%
7/28 • Number of events 15 • Baseline to 9 months
|
33.3%
10/30 • Number of events 12 • Baseline to 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Post-nasal drip
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
10.0%
3/30 • Number of events 3 • Baseline to 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
28.6%
8/28 • Number of events 18 • Baseline to 9 months
|
16.7%
5/30 • Number of events 18 • Baseline to 9 months
|
|
Eye disorders
dry eyes
|
7.1%
2/28 • Number of events 3 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Musculoskeletal and connective tissue disorders
Backache
|
0.00%
0/28 • Baseline to 9 months
|
13.3%
4/30 • Number of events 4 • Baseline to 9 months
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
3.3%
1/30 • Number of events 1 • Baseline to 9 months
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
7.1%
2/28 • Number of events 2 • Baseline to 9 months
|
0.00%
0/30 • Baseline to 9 months
|
|
Renal and urinary disorders
urinary tract infection
|
3.6%
1/28 • Number of events 1 • Baseline to 9 months
|
6.7%
2/30 • Number of events 4 • Baseline to 9 months
|
|
Infections and infestations
Tooth infection
|
0.00%
0/28 • Baseline to 9 months
|
6.7%
2/30 • Number of events 2 • Baseline to 9 months
|
Additional Information
Steven R. Duncan, MD
University of Alabama at Birmingham
Phone: (205) 934-5017
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place