Trial Outcomes & Findings for A Study to Evaluate the Safety and Tolerability of Oral Ixazomib in Scleroderma-related Lung Disease Patients (NCT NCT04837131)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

7 months

Results posted on

2025-04-06

Participant Flow

Participant milestones

Participant milestones
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Overall Study STARTED	4
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Overall Study Death	1
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1
Overall Study Protocol Violation	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=4 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Age, Continuous	58 years STANDARD_DEVIATION 23.2 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 months

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.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Treatment-emergent Adverse Event (AE)	3 Participants

PRIMARY outcome

Timeframe: 7 months

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

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Adverse Events Leading to Ixazomib Dose Modifications	2 Participants

PRIMARY outcome

Timeframe: 7 months

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

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Adverse Events Leading to Ixazomib Early Discontinuation	2 Participants

PRIMARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change in the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal 2.0 (UCLA SCTC GIT 2.0) Questionnaire Score	-0.09 score on a scale Standard Deviation 0.156

SECONDARY outcome

Timeframe: Baseline, 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. Lower scores indicate less involvement, and higher scores indicate more severe thickening.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change From Baseline in Modified Rodnan Skin Score (MRSS)	-4.33 score on a scale Standard Deviation 11.02

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Chest CT scan not performed on any participants. Data not collected nor analyzed as study was terminated due to low enrollment.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 7 months

FVC is the maximum amount of air a person can forcefully exhale from their lungs after taking a deep breath.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change in Forced Vital Capacity (FVC) % Predicted.	-0.33 percentage of air Standard Deviation 5.51

SECONDARY outcome

Timeframe: Baseline, 24 weeks

TLC is the total maximum amount of air that lungs can hold.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=2 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change in Total Lung Capacity (TLC) % Predicted	5 percentage of air in lungs Standard Deviation 39.11

SECONDARY outcome

Timeframe: Baseline

Population: Mahler Baseline Dyspnea Index was not completed by any subject. Data not collected nor analyzed as study was terminated due to low enrollment.

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). Higher scores indicate lower impairment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Mahler Transitional Dyspnea Index was not completed by any subject. Data not collected nor analyzed as study was terminated due to low enrollment.

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). Higher scores indicate major improvement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Scleroderma Health Assessment Questionnaire was not completed by any subject. Data not collected nor analyzed as study was terminated due to low enrollment.

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"

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=2 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change in Patient Global Assessment of Disease Activity (PtGA)	3.4 score on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change in Physician Global Assessment of Disease Activity (MDGA)	1.7 score on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: American College of Rheumatology Composite Response Index testing was not completed by any subject. Data not collected nor analyzed as study was terminated due to low enrollment.

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. 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 7 months

DLCO is the amount of carbon monoxide (CO) that moves from the lungs to the blood

Outcome measures

Outcome measures
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=3 Participants Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Change in Diffusion Capacity (DLCO) % Predicated	0 percentage of carbon monoxide Standard Deviation 5.30

Adverse Events

Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ixazomib in Patients With Scleroderma-interstitial Lung Disease (ILD) n=4 participants at risk Participants were administered oral ixazomib for six cycles (each cycle is 28 days duration). Ixazomib: Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles
Nervous system disorders Pruritus	50.0% 2/4 • Number of events 3 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Skin and subcutaneous tissue disorders Rash	50.0% 2/4 • Number of events 2 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Gastrointestinal disorders Vomiting	50.0% 2/4 • Number of events 3 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Gastrointestinal disorders Diarrhea	50.0% 2/4 • Number of events 3 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Infections and infestations Fever	25.0% 1/4 • Number of events 2 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Nervous system disorders Hyponatremia	25.0% 1/4 • Number of events 2 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Nervous system disorders Hypokalemia	25.0% 1/4 • Number of events 1 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 1/4 • Number of events 1 • Adverse events were collected from baseline to completion of the post-treatment follow-up visit, approximately 16 months.

Additional Information

Michael Pham, M.D.

Mayo Clinic

Phone: 480-301-8318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place