A Study to Evaluate the Safety and Tolerability of Oral Ixazomib in Scleroderma-related Lung Disease Patients

NCT04837131 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 20-004201
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to learn about the effects of the medication ixazomib in participants with scleroderma/systemic sclerosis including its safety and tolerability, its effects on skin, lungs and other organs, and its effects on overall health and quality of life.

Conditions

Systemic Sclerosis; Scleroderma; Diffuse Systemic Sclerosis; Diffuse Scleroderma; Diffuse Cutaneous Systemic Sclerosis; Diffuse Cutaneous Scleroderma; Progressive Systemic Sclerosis; Progressive Scleroderma; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma;Progressive; Systemic Sclerosis, Diffuse; Systemic; Sclerosis, Progressive; Scleroderma of Lung; Scleroderma With Pulmonary Involvement; Systemic Sclerosis Pulmonary; Systemic Sclerosis With Lung Involvement; Interstitial Lung Disease; Pulmonary Fibrosis Interstitial

Keywords

Scleroderma; Systemic Sclerosis; Interstitial Lung Disease; Ixazomib; Mycophenolate; Treatment

Outcome Measures

Primary Outcomes (4)

• Treatment-emergent Adverse Event (AE)

  The number of participants with at least one treatment-emergent adverse event. Defined as any of the following: Treatment-emergent AEs; Treatment-emergent serious adverse events (SAEs); Treatment-emergent treatment-related AEs; or Treatment-emergent treatment-related SAEs.

  7 months

• Adverse Events Leading to Ixazomib Dose Modifications

  Number of participants with treatment-emergent AEs leading to ixazomib dose modifications.

  7 months

• Adverse Events Leading to Ixazomib Early Discontinuation

  Number of participants with treatment-emergent AEs leading to ixazomib early discontinuation.

  7 months

• Change in the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal 2.0 (UCLA SCTC GIT 2.0) Questionnaire Score

  The UCLA SCTC GIT 2.0 is a self-administered survey consisting of 34 questions (Reflux 1 to 8, Distention/Bloating 9 to 12, Fecal Soilage 13, Diarrhea 14 to 15, Social functioning 16 to 21, Emotional well-being 22 to 30, Constipation 31 to 34). The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health, except for questions 15 and 31, which are scored as 0 (better health) and 1 (worse health). Scores from all scales except the constipation scale are averaged to form a total GIT score from 0 (no gastrointestinal problems) to 3 (most severe) that captures overall burden of severity of scleroderma-associated gastrointestinal involvement.

  Baseline, 7 months

Secondary Outcomes (11)

• Change From Baseline in Modified Rodnan Skin Score (MRSS)

  Baseline, 24 weeks

• Change From Baseline in High Resolution Chest CT Scan Goh Score

  Baseline, 24 weeks

• Change in Forced Vital Capacity (FVC) % Predicted.

  Baseline, 7 months

• Change in Total Lung Capacity (TLC) % Predicted

  Baseline, 24 weeks

• Severity of Dyspnea at Baseline (Mahler Baseline Dyspnea Index)

  Baseline

Study Arms (1)

Ixazomib in patients with scleroderma-interstitial lung disease (ILD)

EXPERIMENTAL

Participants will be administered oral ixazomib for six cycles (each cycle is 28 days duration).

Drug: Ixazomib

Interventions

Ixazomib DRUG

Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles

Ixazomib in patients with scleroderma-interstitial lung disease (ILD)

Eligibility Criteria

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

You may qualify if:

• Male and female patients, age ≥18 years at time of signing informed written consent
• Confirmed diagnosis of diffuse cutaneous systemic sclerosis/scleroderma
• Disease duration not longer than 60 months defined as the time from the first non-Raynaud phenomenon manifestation
• Scleroderma skin thickness score (modified Rodnan skin score) between 15 and 45
• Evidence of scleroderma-related lung involvement on chest CT scan completed within the preceding 3 months or at screening study visit
• Pulmonary function testing demonstrating FVC ≥45% predicted and DLCO ≥40% predicted at screening study visit
• Resting transthoracic echocardiogram within the preceding 6 months or at screening study visit without evidence of pulmonary artery hypertension
• Stable mycophenolate dose during the preceding 3 months for those who are taking mycophenolate. Mycophenolate use is not an eligibility requirement to participate; but those participants already using mycophenolate at screening study visit will continue taking the medication throughout the entire study.
• Willingness to undergo supervised withdrawal during the first 90 days of the study of any other medication besides mycophenolate used specifically as treatment of scleroderma-related interstitial lung disease with confirmed stable pulmonary status.
• Willingness to undergo supervised withdrawal during the first 90 days of the study of any other prohibited medications with confirmed stable status.
• Able to understand and sign a written informed consent form
• Able to understand the importance of adhering to study treatment and the study protocol, and willing and able to follow all study requirements, including the concomitant medication restrictions, throughout the study
• Practice birth control requirements for sexually active female participants including option of abstinence for the entire study and for at least 90 days after the last dose of study medication
• Practice birth control requirements for sexually active male participants or partners including option of abstinence for the entire study and for at least 90 days after the last dose of study medication

You may not qualify if:

• Pulmonary artery hypertension under treatment
• Evidence of clinically significant pulmonary hypertension or left ventricular dysfunction with left ventricular ejection fraction \< 40% from either prior heart catheterization or resting transthoracic echocardiography within the preceding 6 months.
• Evidence of significant gastrointestinal involvement by scleroderma as assessed by the University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract multi-item questionnaire, 2.0 (\[UCLA SCTC GIT 2.0) at screening study visit.
• Known esophageal stricture sufficient to limit the ability to swallow oral medication
• Prior history of scleroderma renal crisis
• Another connective-tissue disorder (eg, rheumatoid arthritis, systemic lupus erythematosus)
• Any other significant pulmonary disorder (e.g., chronic obstructive pulmonary disease, emphysema, adult moderate to severe asthma)
• Significant environmental exposure known to cause pulmonary fibrosis including, but not limited to, drugs (e.g., amiodarone), asbestos, beryllium, radiation, or domestic birds or other exposures associated with hypersensitivity pneumonitis
• Unstable or deteriorating cardiac disease within the preceding 6 months including but not limited to unstable angina pectoris, myocardial infarction (heart attack), heart failure requiring hospitalization, poorly controlled heart arrhythmia, or significant pericardial effusion/fluid collection around the heart
• Known liver disease (e.g., chronic hepatitis or cirrhosis)
• Significant abnormality of liver function tests
• Significant kidney function impairment of any cause as evidenced by creatinine clearance \<30 mL/min
• Known active or suspected peptic (stomach) ulcer
• Known active hematologic blood-related disorder other than anemia of chronic disease or iron deficiency anemia
• Significant abnormality of blood count including hemoglobin ≤ 8.0 gm/dl, absolute neutrophil count ≤ 1000, or platelet count ≤ 75,000

Sponsors & Collaborators

• Michael M. Pham: lead

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Related Links

• A Study to Evaluate the Safety and Tolerability of Oral Ixazomib in Scleroderma-related Lung Disease Patients

MeSH Terms

Conditions

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

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated due to low enrollment.

Results Point of Contact

• Title: Michael Pham, M.D.
• Organization: Mayo Clinic

Pham.Michael@mayo.edu

480-301-8318

Study Officials

• Michael Pham, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Regulatory Sponsor and Principal Investigator

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 8, 2021
• Study Start: April 28, 2021
• Primary Completion: February 23, 2024
• Study Completion: February 23, 2024
• Last Updated: April 6, 2025
• Results First Posted: April 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)