Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis

NCT02370693 | Completed Phase 2 Results DMC

• 2 other identifiers: R341R34HL122558-01A1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lung Diseases, Interstitial; Systemic Sclerosis; Scleroderma

Keywords

mycophenolate; lung scarring

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  24 weeks

• Change of Lung Function Measured by Forced Vital Capacity (FVC) Between Baseline and 24 Weeks

  24 weeks

Study Arms (2)

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

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

Drug: Placebo; Drug: Mycophenolate mofetil

Interventions

Bortezomib DRUG

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

Also known as: Velcade

bortezomib plus mycophenolate mofetil

Placebo DRUG

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 known as: normal saline

Placebo plus mycophenolate mofetil

Mycophenolate mofetil DRUG

Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks

Also known as: CellCept

Placebo plus mycophenolate mofetil; bortezomib plus mycophenolate mofetil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Northwestern University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Lung Diseases, Interstitial; Scleroderma, Systemic; Scleroderma, Diffuse

Interventions

Bortezomib; Saline Solution; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Manu Jain, MD
• Organization: Northwestern University

m-jain@northwestern.edu

312-503-4242

Study Officials

• Manu Jain, MD, MSc

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Medicine-Pulmonary and Pediatrics

Study Record Dates

• First Submitted: February 11, 2015
• First Posted: February 25, 2015
• Study Start: March 1, 2016
• Primary Completion: December 16, 2019
• Study Completion: January 1, 2020
• Last Updated: August 25, 2021
• Results First Posted: August 25, 2021

Record last verified: 2021-08

Locations

US (1)