Trial Outcomes & Findings for Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in People With Indolent Systemic Mastocytosis (NCT NCT03770273)

NCT ID: NCT03770273

Last Updated: 2024-12-17

Results Overview

The Mastocytosis Quality of Life Questionnaire (MC-QoL) is a validated health-related quality of life (QoL) survey for patients with mastocytosis that consists of 27 items and is divided into four domains: symptoms, social life/functioning, emotions, and skin. Each item has five options scored from 0-4 for a total minimum score of zero and maximum score of 108. The raw scores were transformed to a 0 to 100 scale. The overall disease impairment on QoL is measured by assessing both the total score and the scores of each domain with higher scores of 25% or greater indicating a higher QoL impairment. The percent change in QoL from baseline to 16 weeks post-initiation of study for participants was computed as \[(Baseline QoL - 16-week QoL)/Baseline QoL\] × 100\]. Positive value indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Baseline and 16-week post-initiation of study

Results posted on

2024-12-17

Participant Flow

21 participants were enrolled in the study and five participants were deemed ineligible and excluded from study

Participant milestones

Participant milestones
Measure
Drug: Sarilumab
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Overall Study
STARTED
8
8
Overall Study
COMPLETED
5
7
Overall Study
NOT COMPLETED
3
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Drug: Sarilumab
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Overall Study
Adverse Event
2
0
Overall Study
Lost to Follow-up
1
1

Baseline Characteristics

Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in People With Indolent Systemic Mastocytosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Drug: Sarilumab
n=8 Participants
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=8 Participants
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Total
n=16 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
7 Participants
n=5 Participants
5 Participants
n=7 Participants
12 Participants
n=5 Participants
Age, Categorical
>=65 years
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
3 Participants
n=7 Participants
8 Participants
n=5 Participants
Sex: Female, Male
Male
3 Participants
n=5 Participants
5 Participants
n=7 Participants
8 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
8 Participants
n=5 Participants
8 Participants
n=7 Participants
16 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
Race (NIH/OMB)
White
7 Participants
n=5 Participants
5 Participants
n=7 Participants
12 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 16-week post-initiation of study

Population: Modified Intent-to-Treat (mITT) participants who completed questionnaire during the blinded phase of the study. One participant did not complete study during the blinded phase so was excluded from analysis.

The Mastocytosis Quality of Life Questionnaire (MC-QoL) is a validated health-related quality of life (QoL) survey for patients with mastocytosis that consists of 27 items and is divided into four domains: symptoms, social life/functioning, emotions, and skin. Each item has five options scored from 0-4 for a total minimum score of zero and maximum score of 108. The raw scores were transformed to a 0 to 100 scale. The overall disease impairment on QoL is measured by assessing both the total score and the scores of each domain with higher scores of 25% or greater indicating a higher QoL impairment. The percent change in QoL from baseline to 16 weeks post-initiation of study for participants was computed as \[(Baseline QoL - 16-week QoL)/Baseline QoL\] × 100\]. Positive value indicates improvement.

Outcome measures

Outcome measures
Measure
Drug: Sarilumab
n=8 Participants
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=7 Participants
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Percent Change in Quality of Life (QoL) Using Mastocytosis Quality of Life Questionnaire (MC-QoL)
38.98 percentage of change in quality of life
Interval 28.83 to 49.13
33.02 percentage of change in quality of life
Interval 22.17 to 43.88

PRIMARY outcome

Timeframe: Up to 32 weeks post initiation of study

Population: Modified Intent-to-Treat (mITT) participants who completed questionnaire during the blinded phase of the study. One participant did not complete study during the blinded phase so was excluded from analysis.

Severity of adverse event by grade using Terminology Criteria for Adverse Events (CTCAE) version 5.0: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activity of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living (ADL). Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event

Outcome measures

Outcome measures
Measure
Drug: Sarilumab
n=8 Participants
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=7 Participants
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Number of Participants With Adverse Events by Grade
Grade 1
7 Participants
6 Participants
Number of Participants With Adverse Events by Grade
Grade 2
6 Participants
3 Participants
Number of Participants With Adverse Events by Grade
Grade 3
2 Participants
2 Participants
Number of Participants With Adverse Events by Grade
Grade 4
0 Participants
0 Participants
Number of Participants With Adverse Events by Grade
Grade 5
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline and 16-week post-initiation of study

Population: Modified Intent-to-Treat (mITT) participants who completed questionnaire during the blinded phase of the study. One participant did not complete study during the blinded phase so was excluded from analysis.

The Memorial Symptom Assessment Scale (MSAS) is used to evaluate a patient's experience with 32 symptoms over the course of the previous week. Symptoms are evaluated by severity (0 = not at all to 4 = very severe) and distress (0 = not at all to 4 = very much\] for eight of the symptoms, and for severity, distress, and frequency (0 = not at all to 4 = almost constantly) for the remaining 24 symptoms for a total minimum score of zero and maximum score of 352. Higher score indicates worsening condition. The result is calculated by taking the average of the scores for the 32 questions for baseline and week 16 post initiation of study. The percent change in quality of life (QoL) from baseline to 16 weeks post-initiation of study for participants was computed as \[(Baseline QoL - 16-week QoL)/Baseline QoL\] × 100\]. Positive value indicates improvement.

Outcome measures

Outcome measures
Measure
Drug: Sarilumab
n=8 Participants
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=7 Participants
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Percent Change in Quality of Life (QoL) Using the Memorial Symptom Assessment Scale (MSAS)
0.767 percentage of change in quality of life
Interval 0.54 to 0.99
0.503 percentage of change in quality of life
Interval 0.26 to 0.74

SECONDARY outcome

Timeframe: Baseline and 16-week post-initiation of study

Population: Modified Intent-to-Treat (mITT) participants who completed questionnaire during the blinded phase of the study. One participant did not complete study during the blinded phase so was excluded from analysis.

The Mastocytosis Quality of Life Questionnaire (MQLQ) is disease specific quality of life questionnaire consisting of 49 questions to assess the effect of mastocytosis on daily life. It includes the role of mastocytosis in 8 domains: fatigue and mental health, anaphylaxis, bone symptoms, unfamiliarity (low awareness), flushing, general symptoms, skin symptoms, and triggers. Each item in the 49 questions has seven options scored from 0-6 with a minimum total score of zero and a maximum total score of 294. Higher score indicates worsening condition. The result is calculated by summing scores from all 49 items for baseline and week 16 post initiation of study. The percent change in QoL from baseline to 16 weeks post-initiation of study for participants was computed as \[(Baseline QoL - 16-week QoL)/Baseline QoL\] × 100\]. Positive value indicates improvement.

Outcome measures

Outcome measures
Measure
Drug: Sarilumab
n=8 Participants
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=7 Participants
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Percent Change in Quality of Life (QoL) Using Mastocytosis Quality of Life Questionnaire (MQLQ)
111.02 percentage of change in quality of life
Interval 88.51 to 133.53
100.26 percentage of change in quality of life
Interval 76.19 to 124.33

SECONDARY outcome

Timeframe: Baseline and 16-week post-initiation of study

Population: Modified Intent-to-Treat (mITT) participants who completed questionnaire during the blinded phase of the study. One participant did not complete study during the blinded phase so was excluded from analysis.

The Mastocytosis Symptoms Assessment Form (MSAF) is a 22-item questionnaire that assesses the severity of symptoms with an 11-point numeric rating scale, where "0 = No symptom" and "10 = Worst imaginable symptom" for a total minimum score of zero and total maximum score of 220. Higher score indicates worsening condition. The result is calculated by summing scores from all 22 items for baseline and week 16 post initiation of study. The percent change in QoL from baseline to 16 weeks post-initiation of study for participants was computed as \[(Baseline QoL - 16-week QoL)/Baseline QoL\] × 100\]. Positive value indicates improvement.

Outcome measures

Outcome measures
Measure
Drug: Sarilumab
n=8 Participants
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=7 Participants
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Percent Change in Quality of Life (QoL) Using Mastocytosis Symptoms Assessment Form (MSAF)
55.83 percentage of change in quality of life
Interval 43.0 to 68.66
42.20 percentage of change in quality of life
Interval 28.48 to 55.91

Adverse Events

Drug: Sarilumab

Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Drug: Sarilumab
n=8 participants at risk
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=8 participants at risk
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Gastrointestinal disorders
Large intestine perforation
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention

Other adverse events

Other adverse events
Measure
Drug: Sarilumab
n=8 participants at risk
Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)
Placebo
n=8 participants at risk
Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)
Blood and lymphatic system disorders
Eosinophilia
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Cardiac disorders
Dizziness
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Cardiac disorders
Palpitations
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Ear and labyrinth disorders
Ear pain
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Eye disorders
Eye pain
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Gastrointestinal disorders
Constipation
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Gastrointestinal disorders
Diarrhea
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Gastrointestinal disorders
Nausea
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Gastrointestinal disorders
Pharyngitis
25.0%
2/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Gastrointestinal disorders
Stomatitis
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Gastrointestinal disorders
Vomiting
12.5%
1/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
General disorders
Adverse reaction
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
General disorders
Fatigue
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
General disorders
Influenza like illness
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
General disorders
Injection site bruising
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
General disorders
Injection site erythema
37.5%
3/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
General disorders
Injection site induration
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
General disorders
Injection site reaction
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
General disorders
Irritability
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
General disorders
Pain
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
General disorders
Procedural pain
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Infections and infestations
Bacterial vaginosis
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Infections and infestations
Candida infection
37.5%
3/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Injury, poisoning and procedural complications
Procedural pain
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
Alanine aminotransferase increased
25.0%
2/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
Aspartate aminotransferase increased
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
Blood bilirubin increased
25.0%
2/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
Blood chloride increased
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Investigations
Blood cholesterol increased
25.0%
2/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
Lymphocyte count decreased
12.5%
1/8 • Up to 16 weeks after final dose of intervention
37.5%
3/8 • Up to 16 weeks after final dose of intervention
Investigations
Neutrophil count decreased
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
Platelet count decreased
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Investigations
White blood cell count decreased
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Metabolism and nutrition disorders
Abnormal loss of weight
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Metabolism and nutrition disorders
Hypercalcemia
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Metabolism and nutrition disorders
Hyperglycemia
25.0%
2/8 • Up to 16 weeks after final dose of intervention
25.0%
2/8 • Up to 16 weeks after final dose of intervention
Metabolism and nutrition disorders
Hypertriglyceridemia
37.5%
3/8 • Up to 16 weeks after final dose of intervention
37.5%
3/8 • Up to 16 weeks after final dose of intervention
Musculoskeletal and connective tissue disorders
Pain in extremity
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Nervous system disorders
Insomnia
12.5%
1/8 • Up to 16 weeks after final dose of intervention
25.0%
2/8 • Up to 16 weeks after final dose of intervention
Nervous system disorders
Memory impairment
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Nervous system disorders
Presyncope
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Nervous system disorders
Sensory disturbance
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Renal and urinary disorders
Genitourinary tract infection
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Renal and urinary disorders
Urinary retention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Reproductive system and breast disorders
Dysmenorrhea
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Reproductive system and breast disorders
Perimenopausal symptoms
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Respiratory, thoracic and mediastinal disorders
Bronchitis
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Respiratory, thoracic and mediastinal disorders
Chest discomfort
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Respiratory, thoracic and mediastinal disorders
Cough
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Respiratory, thoracic and mediastinal disorders
Nasal congestion
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Skin and subcutaneous tissue disorders
Dry skin
0.00%
0/8 • Up to 16 weeks after final dose of intervention
12.5%
1/8 • Up to 16 weeks after final dose of intervention
Skin and subcutaneous tissue disorders
Pruritus
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Skin and subcutaneous tissue disorders
Rash
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Skin and subcutaneous tissue disorders
Urticaria
12.5%
1/8 • Up to 16 weeks after final dose of intervention
0.00%
0/8 • Up to 16 weeks after final dose of intervention
Vascular disorders
Hypertension
62.5%
5/8 • Up to 16 weeks after final dose of intervention
62.5%
5/8 • Up to 16 weeks after final dose of intervention

Additional Information

Hirsh Komarow

National Institute of Allergy and Infectious Diseases

Phone: +1 301 594 2197

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place