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Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis

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ClinicalTrials.gov Identifier: NCT02370693
Recruitment Status : Completed
First Posted : February 25, 2015
Results First Posted : August 25, 2021
Last Update Posted : August 25, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Manu Jain, Northwestern University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Lung Diseases, Interstitial
Systemic Sclerosis
Scleroderma
Interventions Drug: Bortezomib
Drug: Placebo
Drug: Mycophenolate mofetil
Enrollment 9
Recruitment Details  
Pre-assignment Details 2 subjects were enrolled (signed consent form) but did not continue through the screening process far enough to reach randomization.
Arm/Group Title Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Hide Arm/Group Description

Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Period Title: Overall Study
Started 3 4
Completed 2 3
Not Completed 1 1
Arm/Group Title Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil Enrolled But Not Randomized Total
Hide Arm/Group Description

Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Subjects who were enrolled (signed consent form) but did not continue through the screening process far enough to reach randomization. Total of all reporting groups
Overall Number of Baseline Participants 3 4 2 9
Hide Baseline Analysis Population Description
2 subjects were enrolled (signed consent form) but did not continue through the screening process far enough to reach randomization.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 2 participants 9 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  66.7%
4
 100.0%
2
 100.0%
8
  88.9%
>=65 years
1
  33.3%
0
   0.0%
0
   0.0%
1
  11.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 4 participants 2 participants 9 participants
59.4  (8.1) 52.3  (4.6) 42.6  (10.4) 52.6  (8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 2 participants 9 participants
Female
2
  66.7%
2
  50.0%
0
   0.0%
4
  44.4%
Male
1
  33.3%
2
  50.0%
2
 100.0%
5
  55.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 2 participants 9 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
  25.0%
0
   0.0%
1
  11.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
3
 100.0%
3
  75.0%
2
 100.0%
8
  88.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 4 participants 2 participants 9 participants
3 4 2 9
1.Primary Outcome
Title Number of Participants With Serious Adverse Events
Hide Description To assess the safety and tolerability of bortezomib with mycophenolate mofetil assessed by the incidence of serious adverse events.
Time Frame First dosing day to last study visit day: Mean duration 8 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose.
Arm/Group Title Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Hide Arm/Group Description:

Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Overall Number of Participants Analyzed 3 4
Mean (Standard Deviation)
Unit of Measure: Number of Participants with Serious Adve
0.33  (.58) 0.25  (.50)
2.Secondary Outcome
Title Change of Skin Fibrosis Measured by the Rodnan Skin Score Between Baseline and 24 Weeks
Hide Description The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness that sums individual scores of skin thickness (0 - No Thickening, 1 - Mild Thickening, 2 - Moderate Thickening, 3 - Severe Thickening) measured at 17 body sites to reach a total score (Range: 0 to 51, higher value representing thicker skin). The Score is used as a surrogate for disease activity and severity, and a worsening score over time is associated with worse outcomes.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who had comparable skin score data.
Arm/Group Title Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Hide Arm/Group Description:

Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Overall Number of Participants Analyzed 3 3
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
-3.00  (2.65) -0.33  (0.58)
3.Secondary Outcome
Title Change of Lung Function Measured by Forced Vital Capacity (FVC) Between Baseline and 24 Weeks
Hide Description Forced vital capacity, or FVC, is the amount in liters of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It measures the effect that lung disease has on a person's ability to inhale and exhale. Higher values are better, and decreases over time can indicate disease progression.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who had comparable forced vital capacity data.
Arm/Group Title Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Hide Arm/Group Description:

Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Overall Number of Participants Analyzed 3 3
Mean (Standard Deviation)
Unit of Measure: Percentage of change in FVC %predicted
0.51  (0.55) -0.69  (1.02)
Time Frame First dosing day to last study visit day: Mean duration 8 months.
Adverse Event Reporting Description Adverse event information collected by study team at each study visit.
 
Arm/Group Title Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Hide Arm/Group Description

Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks

Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks

Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

All-Cause Mortality
Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)      0/4 (0.00%)    
Hide Serious Adverse Events
Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      1/4 (25.00%)    
Infections and infestations     
Herpes Zoster Infection   1/3 (33.33%)  1 0/4 (0.00%)  0
Respiratory Syncytial Virus Bilaterial Pneumonia   0/3 (0.00%)  0 1/4 (25.00%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bortezomib Plus Mycophenolate Mofetil Placebo Plus Mycophenolate Mofetil
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      4/4 (100.00%)    
Endocrine disorders     
Pre-diabetes   0/3 (0.00%)  0 1/4 (25.00%)  1
Eye disorders     
Dry eyes   0/3 (0.00%)  0 1/4 (25.00%)  1
Gastrointestinal disorders     
Acid reflux   0/3 (0.00%)  0 1/4 (25.00%)  1
Bloating   0/3 (0.00%)  0 1/4 (25.00%)  1
Diarrhea   2/3 (66.67%)  5 1/4 (25.00%)  1
Gastroparesis   1/3 (33.33%)  1 0/4 (0.00%)  0
Nausea   2/3 (66.67%)  14 0/4 (0.00%)  0
Upset stomach   1/3 (33.33%)  2 0/4 (0.00%)  0
Vomiting due to coughing   1/3 (33.33%)  1 0/4 (0.00%)  0
Worsening diarrhea   1/3 (33.33%)  1 0/4 (0.00%)  0
General disorders     
Ache on forehead and eyelids   0/3 (0.00%)  0 1/4 (25.00%)  1
Chills   1/3 (33.33%)  1 0/4 (0.00%)  0
Cold sweats   1/3 (33.33%)  1 0/4 (0.00%)  0
Fatigue   2/3 (66.67%)  3 0/4 (0.00%)  0
Headache   3/3 (100.00%)  9 1/4 (25.00%)  2
Shaking   1/3 (33.33%)  1 0/4 (0.00%)  0
Weight loss of ~10 lbs   1/3 (33.33%)  1 0/4 (0.00%)  0
Worsened body aches   0/3 (0.00%)  0 1/4 (25.00%)  1
Worsened fatigue   0/3 (0.00%)  0 1/4 (25.00%)  1
Infections and infestations     
Cold   0/3 (0.00%)  0 1/4 (25.00%)  1
Injury, poisoning and procedural complications     
Bruising at injection site   1/3 (33.33%)  1 0/4 (0.00%)  0
Burning sensation at injection site   1/3 (33.33%)  2 0/4 (0.00%)  0
Pain at injection site   1/3 (33.33%)  1 0/4 (0.00%)  0
Redness at injection site   3/3 (100.00%)  6 0/4 (0.00%)  0
Skin peeling at injection site   1/3 (33.33%)  1 0/4 (0.00%)  0
Tingling at injection site   1/3 (33.33%)  1 0/4 (0.00%)  0
Soreness at injection site   1/3 (33.33%)  1 0/4 (0.00%)  0
Warmth at injection site   1/3 (33.33%)  1 0/4 (0.00%)  0
Metabolism and nutrition disorders     
High cholesterol   0/3 (0.00%)  0 1/4 (25.00%)  1
Musculoskeletal and connective tissue disorders     
Bach ache   0/3 (0.00%)  0 1/4 (25.00%)  1
Body aches   0/3 (0.00%)  0 1/4 (25.00%)  1
Left ankle pain   0/3 (0.00%)  0 1/4 (25.00%)  1
Pain in right shoulder   1/3 (33.33%)  1 0/4 (0.00%)  0
Right side back muscle spasm   1/3 (33.33%)  1 0/4 (0.00%)  0
Nervous system disorders     
Tingling sensation on face   1/3 (33.33%)  1 0/4 (0.00%)  0
Renal and urinary disorders     
Urinary tract infection   1/3 (33.33%)  1 2/4 (50.00%)  2
Respiratory, thoracic and mediastinal disorders     
Cough   0/3 (0.00%)  0 1/4 (25.00%)  1
Cough with increased mucus   0/3 (0.00%)  0 1/4 (25.00%)  1
Dry cough   0/3 (0.00%)  0 1/4 (25.00%)  2
Dry throat   1/3 (33.33%)  1 0/4 (0.00%)  0
Nasal congestion   1/3 (33.33%)  1 1/4 (25.00%)  1
Productive cough   1/3 (33.33%)  1 0/4 (0.00%)  0
Prolonged coughing episode   1/3 (33.33%)  1 0/4 (0.00%)  0
Runny nose   1/3 (33.33%)  3 0/4 (0.00%)  0
Sore throat   1/3 (33.33%)  2 0/4 (0.00%)  0
Worsened cough   1/3 (33.33%)  3 0/4 (0.00%)  0
Worsening shortness of breath   0/3 (0.00%)  0 1/4 (25.00%)  1
Skin and subcutaneous tissue disorders     
Dry Skin   0/3 (0.00%)  0 1/4 (25.00%)  1
Surgical and medical procedures     
Tooth extraction   1/3 (33.33%)  1 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Manu Jain, MD
Organization: Northwestern University
Phone: 312-503-4242
EMail: m-jain@northwestern.edu
Layout table for additonal information
Responsible Party: Manu Jain, Northwestern University
ClinicalTrials.gov Identifier: NCT02370693    
Other Study ID Numbers: R34
1R34HL122558-01A1 ( U.S. NIH Grant/Contract )
First Submitted: February 11, 2015
First Posted: February 25, 2015
Results First Submitted: June 14, 2021
Results First Posted: August 25, 2021
Last Update Posted: August 25, 2021