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

NCT03770273 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 19002719-I-0027
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Mast cells help the body fight disease and heal wounds. People with indolent systemic mastocytosis (ISM) make too many mast cells. This causes pain, tiredness, digestive problems, and other symptoms. Researchers think the drug sarilumab could help. Objective: To see if sarilumab is a safe and effective treatment for people with ISM. Eligibility: Adults ages 18-75 with ISM who are enrolled in NIH study 02-I-0277 Design: Participants will be screened with:

• Physical exam
• Medical history
• Blood and urine tests
• Questionnaires
• Bone marrow removed by a needle inserted into the hip bone
• Ultrasound of the abdomen
• Photographs of the skin Participants will repeat some screening tests at study visits. Participants will have a baseline visit in the hospital for 3 days. They will:
• Be assigned to get either the study drug or a placebo. They will not know which one they get.
• Have a skin punch biopsy: An instrument will remove a small piece of skin.
• Get their first drug dose injected under their skin Participants will keep a side effect and medication diary during the study. Participants will visit the clinic to get a drug dose every 2 weeks, for a total of 8 doses. Participants will have a visit 2 weeks after their final dose. It will last up to 2 days. Participants will have another visit 12 weeks later. Participants may then continue this study for 1 more year. Those who continue will get sarilumab, even if they previously got the placebo, every 2 weeks. They will have visits every 6 weeks, and then every 3 months.

Conditions

Indolent Systemic Mastocytosis

Keywords

Cytokine; Monoclonal Therapy; Interleukin-6; Mast Cell; Bone Marrow

Outcome Measures

Primary Outcomes (2)

• Percent Change in Quality of Life (QoL) Using Mastocytosis Quality of Life Questionnaire (MC-QoL)

  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.

  Baseline and 16-week post-initiation of study

• Number of Participants With Adverse Events by Grade

  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

  Up to 32 weeks post initiation of study

Secondary Outcomes (3)

• Percent Change in Quality of Life (QoL) Using the Memorial Symptom Assessment Scale (MSAS)

  Baseline and 16-week post-initiation of study

• Percent Change in Quality of Life (QoL) Using Mastocytosis Quality of Life Questionnaire (MQLQ)

  Baseline and 16-week post-initiation of study

• Percent Change in Quality of Life (QoL) Using Mastocytosis Symptoms Assessment Form (MSAF)

  Baseline and 16-week post-initiation of study

Study Arms (2)

Drug: sarilumab

ACTIVE COMPARATOR

Participants with indolent systemic mastocytosis receive sarilumab 200 mg (1.14 ml) subcutaneous injection every two weeks for 16 weeks (8 doses total)

Biological: sarilumab

Placebo

ACTIVE COMPARATOR

Participants with indolent systemic mastocytosis receive placebo subcutaneous injection every two weeks for 16 week (8 doses total)

Other: Placebo

Interventions

sarilumab BIOLOGICAL

Sarilumab is a fully human anti-IL-6Rα monoclonal antibody that binds membrane-bound and soluble human IL-6R and has been shown to inhibit IL-6 signaling.

Drug: sarilumab

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be enrolled in this study:
• Male or female participant greater than or equal to 18 and \< 75 years of age at screening.
• Enrolled on NIAID protocol 02-I-0277.
• Documented pathologic diagnosis of ISM.
• Mc-QoL score of at least 25% (which suggests participant is at least somewhat affected by all Mc-QoL questions).
• Willing and able to undergo a bone marrow biopsy and aspirate.
• Absolute neutrophil count (ANC) greater than or equal to 2000/mL.
• Hemoglobin greater than or equal to 12.0 g/dL (males), greater than or equal to 11 g/dL (females).
• Platelet count greater than or equal to 150,000/microliters.
• Alanine transaminase (ALT) and aspartate transaminase (AST) \< 1.5 times the upper limit of normal (ULN).
• Willing to allow storage of blood and bone marrow for future use in medical research.
• Willing to allow genetic testing on biospecimens.
• Able to provide informed consent.
• Participants who can become pregnant must agree to use adequate contraception when engaging in sexual activities that can result in pregnancy. Adequate contraception must be used consistently, beginning at least 1 month before the beginning of dosing and lasting until 3 months after the final dose of study drug. Acceptable methods of contraception include the following:
• Hormonal contraception (non-oral only).

You may not qualify if:

• Individuals meeting any of the following criteria will be excluded from study participation:
• Any abnormality that would be scored as a Grade 4 toxicity on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Only clinically significant lab results will deem the subject ineligible
• Infected with HIV or has other known immunodeficiency.
• Has an active infection, including localized infection.
• Active diverticulitis.
• Active or chronic viral hepatitis.
• Active or latent tuberculosis.
• Use of any other anti-IL-6 or anti-IL-6R agent within 1 year prior to the date informed consent was obtained.
• Use of cytoreductive therapy for mastocytosis within 1 year prior to the date informed consent was obtained.
• Known lymphoma or advanced and metastatic solid tumors on active therapy (including chemotherapy) within 1 year prior to the date informed consent was obtained
• Use of chemotherapy within 1 year prior to the date informed consent was obtained.
• Receipt of any marketed (eg, omalizumab) or investigational biologic or monoclonal antibody reported to affect mast cell activation within 5 half-lives prior to date informed consent was obtained.
• Receipt of intravenous (IV) immunoglobulin within 30 days prior to the date informed consent was obtained.
• Receipt of live attenuated vaccines within 30 days prior to the date informed consent was obtained.
• History of alcohol or drug/abuse within 12 months prior to date informed consent was obtained.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Komarow HD, Wang J, Eisch R, Scott L, Brittain EH, Metcalfe DD. Treatment of indolent systemic mastocytosis with sarilumab is not supported in a randomized trial. J Allergy Clin Immunol Glob. 2025 May 21;4(3):100498. doi: 10.1016/j.jacig.2025.100498. eCollection 2025 Aug.

  PMID: 40529483 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mastocytosis, Systemic

Interventions

sarilumab

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases

Results Point of Contact

• Title: Hirsh Komarow
• Organization: National Institute of Allergy and Infectious Diseases

komarowh@niaid.nih.gov

+1 301 594 2197

Study Officials

• Hirsh D Komarow, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: June 19, 2019
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: December 17, 2024
• Results First Posted: December 17, 2024

Record last verified: 2023-08-24

Data Sharing

• IPD Sharing: Will share
• Time Frame: One year after submission of result
• Access Criteria: Request to PI

Locations

US (1)