Lung Diseases, InterstitialPhase 2NCT02370693
Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis
A Phase 2 study testing Bortezomib and Mycophenolate mofetil in people with Lung Diseases, Interstitial and Systemic Sclerosis, run by Northwestern University at 1 site in United States.
Trial summary
The purpose of this study is to look at whether bortezomib, mycophenolate or the combination of both is better to treat scarring of the lung caused by Systemic Sclerosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Diseases, Interstitial, Systemic Sclerosis, Scleroderma
- What is being tested?
- Bortezomib and Mycophenolate mofetil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to 1 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meet established criteria for diffuse or limited systemic sclerosis (SSc) and evidence of pulmonary at high risk of progression with or without progressive skin disease.
- Definition includes subjects who meet the American College of Rheumatology criteria for scleroderma
- High Risk of disease progression (see rationale) will be defined as follows
- If first non-Raynaud's manifestation of SSc < 36 months, then if any of the following are true: FVC <70% predicted or high-resolution computed tomography (HRCT) maximum fibrosis score >3 or FVC < 85% and modified Rodnan skin score (mRSS) increase > 5 over 6 months Regardless of disease duration
- Fall in FVC > 10% over the preceding 12 months or less in the absence of prior therapy or another identified causative process as assessed by the primary scleroderma physician
- Fall in FVC > 10% over 6 months on at least 12 months of prior therapy
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- Age > 18 years
- Ability to give informed consent.
- Willingness to discontinue present therapy for the duration of the study
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- No evidence of acute infection
- Absolute neutrophil count >1000
- Platelets >75,000
- Stable mycophenolate mofetil dose for 16 weeks
Who cannot join
- Inability to give informed consent or comply with protocol procedures
- FVC < 40% or diffusing capacity of carbon monoxide (DLCO) <30% predicted
- Patient has a platelet count of less than 50,000 within 14 days before enrollment.
- Patient has an absolute neutrophil count of less 1000 within 14 days before enrollment.
- Patient has a calculated or measured creatinine clearance of < 20 ml/minute within 14 days before enrollment.
- Patient has Grade 2 peripheral neuropathy by history within 14 days before enrollment.
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- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (- hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 4 weeks before enrollment
- Serious medical co-morbidity which in the opinion of the investigator makes participation in the study too high risk
- Psychiatric illness likely to interfere with participation in this clinical study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis Grant Number: R34HL122558
The purpose of this study is to look at whether bortezomib, mycophenolate or the combination of both is better to treat scarring of the lung caused by Systemic Sclerosis.
Read the detailed description
Systemic sclerosis (SSc) is a chronic multisystem autoimmune connective tissue disease for which the etiology remains unknown. The prevalence for SSc is between 19-75 cases per 100,000 and it is more frequent in women, with a peak occurrence in the 4th or 5th decade of life. Morbidity and Mortality in SSc are substantial and pulmonary complications are now the leading cause of death among patients with SSc.
Bortezomib is an FDA approved therapy for the treatment of multiple myeloma and other malignancies. The investigators have data that bortezomib inhibits transforming growth factor (TGF) - signaling in vitro and promotes normal repair and prevents against lung fibrosis in the TGF-mediated intratracheal bleomycin mouse model as well as in a mouse model for skin fibrosis. This is consistent with other data in the literature that proteasomal inhibition can prevent the development of fibrosis. Further there are multiple reports on the efficacy of bortezomib in ameliorating chronic graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplant for multiple myeloma. Bortezomib was also well tolerated in the large clinical trials of multiple myeloma patients with neuropathy and thrombocytopenia the primary adverse events. No pulmonary toxicities were reported in these studies.
Mycophenolate mofetil (CellCept or Myfortic) belongs to a class of medications known as immunosuppressives. This medication was used originally in the management of patients with organ transplants, but is now recommended in the treatment of some autoimmune diseases such as SSc.
Mycophenolate mofetil targets an enzyme in the body called inosine monophosphate dehydrogenase that is important for the formation of deoxyribonucleic acid (DNA) in cells. By interfering with DNA, the medication impairs function of immune system cells that become overactive in autoimmune diseases. Mycophenolate mofetil is currently approved in the treatment of patients with SSc.
This study is being conducted to establish the safety and tolerability of bortezomib in SSc patients at high risk for pulmonary disease progression. In addition, the study will examine the effect of bortezomib on the rate of forced vital capacity (FVC) decline (a physiologic parameter closely associated with disease outcome) and other clinical parameters. In addition the investigators will also measure the effect of bortezomib on biomarkers associated with fibroblast activation. If successful, the study will provide the rationale for a multi-center placebo controlled trial to test the efficacy of bortezomib in SSc patients at high risk for progressive pulmonary disease.
- Conditions
- Lung Diseases, Interstitial, Systemic Sclerosis, Scleroderma
- Being tested
- Bortezomib, Placebo, Mycophenolate mofetil
- Keywords
- mycophenolate, lung scarring
- Medical subject headings
- Lung Diseases, Interstitial, Scleroderma, Systemic, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
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
PlaceboDrug
Also called normal saline
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
Also called CellCept
Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| bortezomib plus mycophenolate mofetil | Active comparator | 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 Receives: Drug: Bortezomib; Drug: Mycophenolate mofetil |
| Placebo plus mycophenolate mofetil | Placebo comparator | 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 Receives: Drug: Placebo; Drug: Mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious Adverse Events
To assess the safety and tolerability of bortezomib with mycophenolate mofetil assessed by the incidence of serious adverse events.
Measured: First dosing day to last study visit day: Mean duration 8 months.
Secondary outcomes (2)
Change of Skin Fibrosis Measured by the Rodnan Skin Score Between Baseline and 24 Weeks
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.
Measured: 24 weeks
Change of Lung Function Measured by Forced Vital Capacity (FVC) Between Baseline and 24 Weeks
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study startMar 2016
- Primary completion16 Dec 2019
- Study completion1 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung Diseases, InterstitialStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Manu Jain, Northwestern University
- Investigators
- Manu Jain, MD, MSc, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370693
- Sponsor's protocol ID
- R34
- Other IDs
- 1R34HL122558-01A1
- Status last verified
- Aug 2021
- First submitted
- 11 Feb 2015
- Last updated
- 25 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis Grant Number: R34HL122558
- ClinicalTrials.gov ID
- NCT02370693
- Acronym / sponsor ID
- R34
- Conditions
- Lung Diseases, Interstitial, Systemic Sclerosis, Scleroderma
- Keywords
- mycophenolate, lung scarring
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2016
- Primary completion
- 16 Dec 2019 (actual)
- Study completion
- 1 Jan 2020 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Posted 25 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to look at whether bortezomib, mycophenolate or the combination of both is better to treat scarring of the lung caused by Systemic Sclerosis.
Detailed description
Systemic sclerosis (SSc) is a chronic multisystem autoimmune connective tissue disease for which the etiology remains unknown. The prevalence for SSc is between 19-75 cases per 100,000 and it is more frequent in women, with a peak occurrence in the 4th or 5th decade of life. Morbidity and Mortality in SSc are substantial and pulmonary complications are now the leading cause of death among patients with SSc.
Bortezomib is an FDA approved therapy for the treatment of multiple myeloma and other malignancies. The investigators have data that bortezomib inhibits transforming growth factor (TGF) - signaling in vitro and promotes normal repair and prevents against lung fibrosis in the TGF-mediated intratracheal bleomycin mouse model as well as in a mouse model for skin fibrosis. This is consistent with other data in the literature that proteasomal inhibition can prevent the development of fibrosis. Further there are multiple reports on the efficacy of bortezomib in ameliorating chronic graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplant for multiple myeloma. Bortezomib was also well tolerated in the large clinical trials of multiple myeloma patients with neuropathy and thrombocytopenia the primary adverse events. No pulmonary toxicities were reported in these studies.
Mycophenolate mofetil (CellCept or Myfortic) belongs to a class of medications known as immunosuppressives. This medication was used originally in the management of patients with organ transplants, but is now recommended in the treatment of some autoimmune diseases such as SSc.
Mycophenolate mofetil targets an enzyme in the body called inosine monophosphate dehydrogenase that is important for the formation of deoxyribonucleic acid (DNA) in cells. By interfering with DNA, the medication impairs function of immune system cells that become overactive in autoimmune diseases. Mycophenolate mofetil is currently approved in the treatment of patients with SSc.
This study is being conducted to establish the safety and tolerability of bortezomib in SSc patients at high risk for pulmonary disease progression. In addition, the study will examine the effect of bortezomib on the rate of forced vital capacity (FVC) decline (a physiologic parameter closely associated with disease outcome) and other clinical parameters. In addition the investigators will also measure the effect of bortezomib on biomarkers associated with fibroblast activation. If successful, the study will provide the rationale for a multi-center placebo controlled trial to test the efficacy of bortezomib in SSc patients at high risk for progressive pulmonary disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| bortezomib plus mycophenolate mofetil | Active comparator | Drug: Bortezomib, Drug: Mycophenolate mofetilBortezomib 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 plus mycophenolate mofetil | Placebo comparator | Drug: Placebo, Drug: Mycophenolate mofetilPlacebo (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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Meet established criteria for diffuse or limited systemic sclerosis (SSc) and evidence of pulmonary at high risk of progression with or without progressive skin disease.
- Definition includes subjects who meet the American College of Rheumatology criteria for scleroderma
- High Risk of disease progression (see rationale) will be defined as follows
- If first non-Raynaud's manifestation of SSc < 36 months, then if any of the following are true: FVC <70% predicted or high-resolution computed tomography (HRCT) maximum fibrosis score >3 or FVC < 85% and modified Rodnan skin score (mRSS) increase > 5 over 6 months Regardless of disease duration
- Fall in FVC > 10% over the preceding 12 months or less in the absence of prior therapy or another identified causative process as assessed by the primary scleroderma physician
Key exclusion criteria (12 listed)
- Inability to give informed consent or comply with protocol procedures
- FVC < 40% or diffusing capacity of carbon monoxide (DLCO) <30% predicted
- Patient has a platelet count of less than 50,000 within 14 days before enrollment.
- Patient has an absolute neutrophil count of less 1000 within 14 days before enrollment.
- Patient has a calculated or measured creatinine clearance of < 20 ml/minute within 14 days before enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: VelcadeBortezomib 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 | Drug | bortezomib plus mycophenolate mofetil |
| PlaceboAlso: normal salinePlacebo (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 | Drug | Placebo plus mycophenolate mofetil |
| Mycophenolate mofetilAlso: CellCeptMycophenolate mofetil 1.5 g twice a day orally for 24 weeks | Drug | Placebo plus mycophenolate mofetil, bortezomib plus mycophenolate mofetil |
Primary outcome
Number of Participants With Serious Adverse Events
Time frame: First dosing day to last study visit day: Mean duration 8 months.
To assess the safety and tolerability of bortezomib with mycophenolate mofetil assessed by the incidence of serious adverse events.
2 secondary outcomes
Change of Skin Fibrosis Measured by the Rodnan Skin Score Between Baseline and 24 Weeks
Time frame: 24 weeks
Change of Lung Function Measured by Forced Vital Capacity (FVC) Between Baseline and 24 Weeks
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manu Jain, MD, MSc principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib and Mycophenolate mofetil in people with Lung Diseases, Interstitial and Systemic Sclerosis, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Serious Adverse Events (time frame: First dosing day to last study visit day: Mean duration 8 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.