A Study to Evaluate the Safety and Tolerability of Oral Ixazomib in Scleroderma-related Lung Disease Patients
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|ClinicalTrials.gov Identifier: NCT04837131|
Recruitment Status : Recruiting
First Posted : April 8, 2021
Last Update Posted : May 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Ixazomib||Phase 2|
The primary objective of this study is to assess the safety and tolerability of oral ixazomib taken on days 1, 8, and 15 of each 28-day treatment cycle for 6 cycles in 12 participants having diffuse systemic sclerosis/scleroderma of less than 5 years duration with non-severe interstitial lung involvement as identified from chest CT scan completed within the preceding 3 months or at study screening visit. All 12 participants will receive oral ixazomib. Reflecting the common use of mycophenolate in the management of scleroderma with complicating interstitial lung disease, 6 of 12 participants who will be enrolled will be already taking mycophenolate at a stable dose for the preceding 3 months and will be allowed to continue taking mycophenolate throughout the entire study prescribed as routine care. Ixazomib will be added to their medications. The remaining 6 of 12 participants meeting the same eligibility criteria will not be using mycophenolate or any other treatment for scleroderma interstitial lung disease at the time of enrollment and will subsequently take ixazomib study medication during participation in this study. Ixazomib dose modification or interruption is allowed for safety and tolerability reasons at any time during the study.
The secondary objective of this study is to assess the effect of ixazomib on scleroderma skin tightness/thickening and its effect on scleroderma interstitial lung disease.
The study includes approximately 13 clinic visits over up to approximately 10 months. Study procedures include medical examinations, blood tests, chest CT scans, pulmonary function tests, echocardiogram, EKG, skin biopsies, and questionnaires.
There is no cost for participation in this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Open-Label Pilot Study of the Safety and Tolerability of Ixazomib Administered Orally to Patients With Scleroderma-Related Interstitial Lung Disease|
|Actual Study Start Date :||April 28, 2021|
|Estimated Primary Completion Date :||April 2024|
|Estimated Study Completion Date :||April 2024|
Experimental: Ixazomib in patients with scleroderma-interstitial lung disease (ILD)
Participants will be administered oral ixazomib for six cycles (each cycle is 28 days duration).
Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
- Number of participants with at least one treatment-emergent adverse event (AE) [ Time Frame: 7 months ]
Treatment-emergent AEs; Treatment-emergent serious adverse events (SAEs); Treatment-emergent treatment-related AEs; Treatment-emergent treatment-related SAEs.
All AEs are summarized by system organ class, preferred Medical Dictionary for Regulatory Activities (MedDRA) term, event severity, and relationship to study medication ixazomib
- Number of participants with treatment-emergent AEs leading to ixazomib dose modifications. [ Time Frame: 7 months ]All AEs are summarized by system organ class, preferred MedDRA term, event severity, and relationship to study medication ixazomib.
- Number of participants with treatment-emergent AEs leading to ixazomib early discontinuation. [ Time Frame: 7 months ]All AEs are summarized by system organ class, preferred MedDRA term, event severity, and relationship to study medication ixazomib.
- Change in the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal 2.0 (UCLA SCTC GIT 2.0) questionnaire score [ Time Frame: Baseline, Each subsequent study visit every 28 days for approximately 7 months ]
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.
Scores will be summarized descriptively.
- Change from baseline in Modified Rodnan Skin Score (MRSS) [ Time Frame: Baseline, 12 weeks, 24 weeks ]
MRSS is a validated clinical semiquantitative assessment of scleroderma skin thickness at 17 prespecified sites on the body, with thickness at each site scored from 0 (uninvolved) to 3 (severe thickening) that are tabulated for a total numerical skin score ranging 0-51. MRSS correlates with internal organ involvement, disease severity, and mortality and is used as outcome measure in clinical trials.
Change of MRSS from baseline at week 12 and week 24 are summarized descriptively without imputation for missing values.
- Change from baseline in high resolution chest CT scan Goh score [ Time Frame: Baseline, 24 weeks ]
Staging extent of scleroderma lung involvement on high resolution chest CT scan by the application of Goh criteria which identified a severity extent threshold of 20% lung involvement yields two cohorts with significantly different 10 year survivorship. Goh scores range 0-100% with a higher score indicating greater extent of lung involvement.
Changes in Goh score are summarized descriptively.
- Change in forced vital capacity (FVC) and diffusion capacity (DLCO) % predicted. [ Time Frame: Baseline, Each study visit every 28 days for approximately 7 months ]FVC and DLCO % predicted change from baseline are summarized descriptively without imputation for missing values.
- Change in total lung capacity (TLC) % predicted [ Time Frame: Baseline, 12 weeks, 24 weeks ]TLC % predicted change from baseline is summarized descriptively without imputation for missing values.
- Severity of dyspnea at baseline (Mahler Baseline Dyspnea Index) [ Time Frame: Baseline ]Severity of dyspnea at baseline is measured with the Mahler Baseline Dyspnea Index (BDI). BDI includes 5 grades of severity from 0 (severe impairment) to 4 (no impairment ) for each of 3 categories (functional impairment; magnitude of task; magnitude of effort) yielding a summation focal score (0-12). BDI focal scores are summarized descriptively without imputation for missing values.
- Dyspnea Status Rating (Mahler Transitional Dyspnea Index) [ Time Frame: 12 weeks, 24 weeks ]Mahler Transitional Dyspnea Index (TDI) rates a participant's dyspnea status relative to baseline. TDI scores range from -3 (major deterioration) to +3 (major improvement) including 0 to indicate no change in status for each of the 3 BDI categories (functional impairment; magnitude of task; magnitude of effort) yielding a summation focal score (-9 to +9). Provision is made for "Z" score if further impairment occurs for reasons other than dyspnea. TDI focal scores are summarized descriptively without imputation for missing values.
- Change in Scleroderma Health Assessment Questionnaire (SHAQ) score [ Time Frame: Baseline, 12 weeks, 24 weeks ]
SHAQ self-assesses function in 8 domains of the Health Assessment Questionnaire Disability Index (HAQ-DI): dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. Highest domain scores 0 (no difficulty) to 3 (unable to do) are summed and divided by 8 to yield Disability Index score as a continuous variable ranging 0 to 3.
SHAQ has:1) a 15-cm Visual Analog Scale (VAS) rating pain with anchors "No Pain" and "Very Severe Pain"; 2) four 15-cm VAS assessing Raynaud phenomenon, digital ulcers, gastrointestinal and lung symptoms with anchors "Does Not Interfere" and "Very Severe Limitation"; and 3) overall disease severity 15-cm VAS with anchors "No Disease" and "Very Severe Disease"
Each VAS scale is converted to a continuous variable (1 cm on VAS = 0.2 points) ranging 0 to 3 which will be summarized descriptively.
- Change in Patient Global Assessment of Disease Activity (PtGA) [ Time Frame: Baseline, 12 weeks, 24 weeks ]
Patient-reported outcome that represents the participant's assessment of his or her current overall health (Question: How was your overall health in the last week?) rated on an 11-point numeric scale anchored at 0 (excellent) to 10 (extremely poor) with higher scores indicating worse disease in terms of severity and damage.
Scores will be summarized descriptively.
- Change in Physician Global Assessment of Disease Activity (MDGA) [ Time Frame: Baseline, 12 weeks, 24 weeks ]
Physician-reported outcome that represents an assessment of the participant's current overall health rated on an 11-point numeric scale anchored at 0 (excellent) to 10 (extremely poor) with higher scores indicating worse disease in terms of severity and damage.
Scores will be summarized descriptively.
- Change in American College of Rheumatology Composite Response Index for clinical trials in early diffuse cutaneous Systemic Sclerosis (ACR CRISS) [ Time Frame: Baseline, 12 weeks, 24 weeks ]
ACR CRISS calculates the predicted probability of improvement in a 2-step process.
Four possible outcomes in Step 1 include worsening of FVC % predicted by at least 15%, new decline of left ventricular ejection fraction to 45% or less attributable to scleroderma and needing treatment, new onset pulmonary arterial hypertension attributable to scleroderma and scleroderma renal crisis. If any one of these outcomes develops as a change from baseline, the participant is classified as not improved (score = 0) regardless of changes in other parameters. The outcome and score are summarized descriptively.
Step 2 calculates change from baseline in the predicted probability of improvement based on combined changes in the mRSS, FVC % predicted, patient global assessment, physician global assessment, and HAQ-DI. The calculated probability ranges from 0 (not improved) to 1.0 where a higher score indicates improvement. Step 2 calculated probability scores are summarized descriptively.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04837131
|Contact: Emily Branch||480-301-9392||Branch.Emily@mayo.edu|
|Contact: Temeka Simmons||480-301-9224||Simmons.Temeka@mayo.edu|
|Principal Investigator:||Leroy Griffing, MD||Mayo Clinic|