Nintedanib Plus Standard of Care Immunosuppression Versus Standard of Care Immunosuppression Alone in Patients With Progressive Fibrotic Myositis Associated - Interstitial Lung Disease: A Randomized, Double-Blind, Exploratory Trial
Overview
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Rohit Aggarwal, MD
- Enrollment
- 49
- Locations
- 10
- Primary Endpoint
- Change in Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) Dyspnea score
Overview
Brief Summary
This research study will evaluate safety and how well the study drug, nintedanib improve symptoms in participants with myositis associated interstitial lung disease (MA-ILD). Interstitial lung disease is a disorder caused by the abnormal accumulation of cells structures between air sacs of the lungs resulting in thickening, stiffness and scarring of the tissues of the lung.
This study will enroll a total of 134 participants across 15 clinical sites located in the United States. A subset of participants will be enrolled remotely via telemedicine utilizing certified mobile home research nurses and various remote monitoring devices.
The research visits may include a physical exam, vital signs (such as blood pressure, heart rate, etc.), pulmonary function tests (PFT and/or home spirometry), Computerized Tomography (or CT) scans of the chest, blood draws, wearing a physical activity monitor and completing questionnaires. Some of these events may be done at home, at a local facility or remotely (via telemedicine).
Detailed Description
Participants enrolled in the study will receive either study drug or placebo for 12 weeks plus the participant's normal standard of care medication for the participant's disease. Placebo is an inactive substance that contains no medicine. Following the initial treatment phase, participants will receive the active study drug (nintedanib) for an additional 12-week period.
Nintedanib is a drug that is currently used and has been approved by the Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF), and has been shown to slow the rate of decline in pulmonary function among patients with IPF as well as interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma. In addition, in March 2020, the FDA approved nintedanib oral capsules to treat patients with chronic fibrosing (scarring) interstitial lung diseases (ILD) with a progressive phenotype (trait).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Subjects, investigators, and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial will remain blinded with regard to the randomized treatment assignments until after the database lock.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject has provided written informed consent
- •Approval from local treating physician (done at pre-screening only for remote patients as well as for local site patients not actively being managed at the local site).
- •Subject lives in the United States
- •Adult: Age ≥ 18 years
- •Subject can speak, read, and understand English or Spanish
- •Subject is willing and capable of performing all study procedures.
- •Validity/repeatability of home spirometry confirmed by PFT lab technician/MD through telemedicine as per American Thoracic Society guidelines.
- •Men and women of reproductive potential must agree to use 2 reliable methods of birth control during the trial period.
- •Clinical diagnosis of myositis or presence of one of the following myositis-specific or -associated autoantibodies).
- •Anti-synthetase autoantibody (Anti-Jo-1, -PL-7, -PL-12, -EJ, -OJ, -KS, -Tyr, -Zo)
Exclusion Criteria
- •Planned major surgical procedures within the trial period of 24 weeks.
- •Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
- •Women of childbearing potential\* not willing or able to use at least two highly effective methods of birth control.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month before study drug administration and agreement to use such a method during study participation and for an additional 28 days after the end of study drug administration.
- •For males of reproductive potential\*\*: use of condoms or other methods to ensure effective contraception with a partner
- •Highly effective contraception examples are:
- •An approved hormonal contraceptive such as oral contraceptives, emergency contraception used as directed, patches, implants, injections, rings, hormonally-impregnated intrauterine device (IUD), or nonhormonal IUD.
- •Abstinence
- •A woman is considered of childbearing potential, i.e. fertile, following menarche, and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, tubal occlusion, and bilateral oophorectomy.
- •A man is considered permanently sterile if a vasectomy has been performed.
Arms & Interventions
Placebo plus Standard of Care, then Nintedanib plus Standard of Care
Placebo twice a day (BID) plus standard of care (SOC) Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.
Intervention: Nintedanib (Drug)
Placebo plus Standard of Care, then Nintedanib plus Standard of Care
Placebo twice a day (BID) plus standard of care (SOC) Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.
Intervention: Placebo (Drug)
Placebo plus Standard of Care, then Nintedanib plus Standard of Care
Placebo twice a day (BID) plus standard of care (SOC) Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.
Intervention: Standard of Care (Drug)
Nintedanib plus Standard of Care
Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.
Intervention: Nintedanib (Drug)
Nintedanib plus Standard of Care
Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.
Intervention: Standard of Care (Drug)
Outcomes
Primary Outcomes
Change in Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) Dyspnea score
Time Frame: Baseline (week 0) to 12 weeks
The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: 1) dyspnea, 2) cough and 3) fatigue as well as a total Symptoms score. The Impacts module yields a single Impacts score. Symptoms and Impacts scores are summed to yield a total L-PF score. Scoring is performed as a summary score, the mean of the dimension ratings multiplied by 100. Summary score range from 0-100, the higher the score the greater the impairment.
Secondary Outcomes
- Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (mL) from baseline to week 12(baseline (week 0) at week 12)
- Time to progression(Baseline (week 0) to week 24)
- Change in Living with Pulmonary Fibrosis Dyspnea score(Baseline (week 0) to week 24)
- Proportion of patients with a relative decline from baseline in FVC (mL) of ≥10%, ≥7.5%, and ≥ 5%(Weeks 12 and 24)
- Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (mL) from baseline to week 24(baseline (week 0) at week 24)
- Time to FVC (mL) improvement and decline from baseline by (≥5%, 7.5%, 10%)(Baseline (week 0) to 24 weeks)
- Absolute and relative change in Forced Vital Capacity (FVC) (mL) from baseline to 12 weeks(Baseline (week 0) to week 12)
- Absolute and relative change in Forced Vital Capacity FVC (%) from baseline to week 12(Baseline (week 0) to week 12)
- Absolute and relative change in Forced Vital Capacity FVC (%) from baseline to week 24(Baseline (week 0) to week 24)
- Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (%) from baseline to week 24(baseline (week 0) at week 24)
- Change in immunosuppressive (IS) regimen(Baseline (Week 0) to week 12)
- Absolute and relative change in Forced Vital Capacity (FVC) (mL) from baseline to 24 weeks(Baseline (week 0) to week 24)
- Change in other Living with Pulmonary Fibrosis scores(Week 12 to week 24)
- Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (%) from baseline to week 12(baseline (week 0) at week 12)
- Proportion of patients with a relative decline from baseline in FVC (%) of ≥10%, ≥7.5%, and ≥ 5%(Weeks 12 and 24)
- Time to FVC (%) improvement and decline from baseline by (≥5%, 7.5%, 10%)(Baseline (week 0) to 24 weeks)
Investigators
Rohit Aggarwal, MD
Professor of Medicine
University of Pittsburgh