Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in People With Indolent Systemic Mastocytosis
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|ClinicalTrials.gov Identifier: NCT03770273|
Recruitment Status : Recruiting
First Posted : December 10, 2018
Last Update Posted : October 9, 2020
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.
To see if sarilumab is a safe and effective treatment for people with ISM.
Adults ages 18-75 with ISM who are enrolled in NIH study 02-I-0277
Participants will be screened with:
- Physical exam
- Medical history
- Blood and urine tests
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Indolent Systemic Mastocytosis||Biological: Sarilumab Other: Placebo||Phase 2|
Systemic mastocytosis is a disorder caused by clonal mast cell proliferation and release of mast cell mediators including tryptase. As a result, mast cell numbers may increase and affect target organs including the dermis (maculopapular cutaneous mastocytosis/urticaria pigmentosa, flushing), gastrointestinal tract (abdominal pain, diarrhea), skeletal system (osteoporosis), hematological system (anemia, thrombocytopenia), and spleen and liver (organomegaly). Patients with indolent (non-aggressive) systemic mastocytosis (ISM) are not candidates for cytoreductive therapy and are generally treated with symptomatic therapy that only partly decreases symptoms. There is, however, a documented association between severity of mastocytosis and elevated serum levels of interleukin (IL)-6. Furthermore, mast cells have been shown to double their rate of division and exhibit increased reactivity and release of mediators when cultured in the presence of IL-6. In addition, in an animal model of mastocytosis, anti-IL-6 has been shown to slow disease progression. In this study, adults with ISM will thus be randomized and treated with sarilumab, a recombinant monoclonal antibody directed against the IL-6 receptor, or receive placebo. Sarilumab is marketed in the United States as Kevzara (Sanofi/Genzyme [Cambridge, MA, USA ]) and is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis. Binding of sarilumab to the IL-6 receptor inhibits IL-6-associated human mast cell signaling and proliferation with a resultant decrease in proliferation and reactivity (decreased mediator release), and therefore is a rational choice for the treatment of ISM.
In this study, participants will be randomized with approximately half of the participants receiving study drug, which will be administered at 200 mg via subcutaneous (SC) injection once every 2 weeks (Q2W) for a total of 16 weeks. The other participants will receive a placebo administered via SC injection Q2W for 16 weeks. Participants will return for a follow-up visit 2 weeks after the final dose (treatment peak), and then again 12 weeks later. Evaluations at study visits will include quality of life and symptom assessments and measurement of serum tryptase levels. Bone marrow examination will be performed at the onset and conclusion of the study. After the week 28 visit, all participants will have the option to continue sarilumab for 52 more weeks, at 200 mg administered via SC injections. Participants will continue to be monitored on a regular basis for safety concerns, as instructed in the study drug s package insert.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2 Randomized Double-Blinded Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in Subjects With Indolent Systemic Mastocytosis|
|Actual Study Start Date :||June 19, 2019|
|Estimated Primary Completion Date :||August 1, 2024|
|Estimated Study Completion Date :||August 1, 2024|
Active Comparator: placebo
8 SC injections of placebo
Active Comparator: sarilumab
8 (SC) injections of 200 mg/1.14 mL of sarilumab over 16 weeks
Sarilumab is a fully human anti-IL-6R-alpha monoclonal antibody that binds membrane-bound and soluble human IL-6R and has been shown to inhibit IL-6 signaling
- Frequency and severity of adverse events (AEs) [ Time Frame: day 0 through week 28 ]frequency and severity of adverse events during the randomized double-blinded placebo-controlled treatment period
- Mastocytosis Quality of Life Questionnaire (MC-QoL). [ Time Frame: 16 weeks post study drug initiation ]QoL at 16 weeks post-initiation of study drug/placebo using the Mastocytosis Quality of Life Questionnaire (MC-QoL).
- mast cells in bone marrow and allelic frequency of D816V [ Time Frame: Day 0 and Week 16 for bone marrow and Day 0, week 16 and week 28 for D816V allelic Frequency ]Reduction of percentage infiltrating mast cells in bone marrow. Decrease in the allelic frequency of D816V using PCR
- Questionnaires MC-Qol, MSAS, SCORMA, MQLQ, MSAF [ Time Frame: Day 0 through Week 28 ]Percent improvement in QoL using MC-QoL, scoring of mastocytosis index (SCORMA), and Memorial Symptom Assessment Scale (MSAS) and the Mastocytosis Quality of Life Questionnaire (MQLQ), and the mastocytosis Symptom Assessment Form (MSAF)
- Reduction in use of medicines and reduction in serum Tryptase [ Time Frame: Day 0 through Week 28 ]Reduction in use of medicines for symptomatic relief, reduction in serum levels of tryptase
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): NCT03770273
|Contact: Robin R. Eisch, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Hirsh D Komarow, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|