Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis

NCT03401060 | Completed Phase 3

• 2 other identifiers: P150918J2016-000596-25
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 11

Brief Summary

The study is looking at the efficacy of subcutaneously administrated denosumab 60 mg every 6 months versus placebo after 3 years, by analyze of lumbar spine bone mineral density (BMD) in systemic mastocytosis. Investigators hypothesize that use of denosumab subcutaneously in patients with osteoporosis related to systemic mastocytosis is effective and safe to improve bone mineral density and prevent new bone events, based on targeted specific RANKL secretion by mast cells and short half-life of denosumab.

Conditions

Osteoporosis; Systemic Mastocytosis

Keywords

Systemic mastocytosis; Osteoporosis; Bone mineral density (BMD); Denosumab; RANKL

Outcome Measures

Primary Outcomes (1)

• Analysis of the lumbar spine bone mineral density (BMD)

  Dual energy x-ray absorptiometry at lumbar spine (L2-L4)

  3 years

Secondary Outcomes (7)

• Occurrence of a low energy vertebral fracture and non vertebral fracture

  Baseline, 1 year, 2 years and 3 years

• BMD at the total left hip

  Baseline, 3 years

• BMD at lumbar spine and the total left hip

  Baseline, 1 year, 2 years

• Biological assays with bone turnover marker of resorption and tryptase levels to assess mastocytosis activity

  Baseline, then every 6 months in 3 years

• Number of serious adverse events to evaluate drug tolerance

  Every 6 months in 3 years

Study Arms (2)

Experimental medication 1

EXPERIMENTAL

Denosumab 60 mg subcutaneously injection with prefilled syringe

Drug: Denosumab

Experimental medication 2

PLACEBO COMPARATOR

NaCl 0.9%, 20ml phial, solution for injection

Drug: Placebo

Interventions

Denosumab DRUG

Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections

Also known as: XGeva®

Experimental medication 1

Placebo DRUG

Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections

Experimental medication 2

Eligibility Criteria

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

You may qualify if:

• Male or female \>/= 18 years of age at time of informed consent
• Willingness and ability to sign informed consent, comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Patient with Indolent systemic or cutaneous mastocytosis according to WHO criteria (Appendix 4) with any specific treatment including corticosteroid, chemotherapy and immunomodulating drugs.
• Patient with:
• osteoporosis defined as bone mineral density T score ≤ -2.5 at the lumbar spine, OR
• osteopenia defined as BMD T-score \>-2,5 and ≤ -1 at the lumbar spine and low energy fracture (defined as fractures that are associated with decreased bone mineral density. Are excluded fractures of skull, face, mandible, metacarpals, fingers, or toes, pathologic fracture, and fracture that are associated with severe trauma).
• (in case of osteoarthritis at the lumbar spine, the T score at left femoral neck or total left hip can be used to define osteoporosis or osteopenia)

You may not qualify if:

• Patient with aggressive mastocytosis or/and Associated Hematologic Non-Mastocytosis Disease (AHNMD)
• Patient with conditions that influence bone metabolism (primitive hyperparathyroidism, hyperaldosteronism, hypercorticism, etc …)
• Patient treated with intravenous bisphosphonate within 1 year prior to enrolment or with any other antiosteoporotic treatment within 3 months before enrolment. (per os bisphosphonate, strontium ranelate) Calcium and vitamin supplementation will be accepted
• Patient previously treated with denosumab
• Patient with hypocalcemia and/or hypo25-hydroxyvitamin D level non substituted prior enrolment
• Woman without contraceptive treatment if of childbearing age.
• Pregnant or breastfeeding woman
• Patient with contraindication to denosumab
• Patient with medical, psychiatric or other conditions that may interfere with patient safety
• Patient with dental problem that need any dental surgery within 6 months after enrolment.
• Patient with clearance of creatinine less than 30 mL/min/1,73m2 (MDRD) or patient receiving dialysis

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• CEREMAST: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (11)

Jean Minjoz Hospital, Dermatology department

Besançon, 25030, France

Location

Caen Hospital, Clinical haematology department

Caen, 14033, France

Location

Estaing Hospital, Cellular therapy and clinical haematology department

Clermont-Ferrand, 63100, France

Location

Lille CHRU Hospital, Internal medicine and clinical immunology department

Lille, 59037, France

Location

La Timone Hospital, Dermatology and cutaneous oncology department

Marseille, 13385, France

Location

Lapeyronie Hospital, Rheumatology and Immunology department

Montpellier, 34295, France

Location

La Pitié-Salpêtrière Hospital, Internal medicine and clinical immunology department

Paris, 75013, France

Location

Cochin Hospital, Rheumatology department

Paris, 75014, France

Location

Necker Hospital, Adult haematology department

Paris, 75015, France

Location

Strasbourg Hospital, Rheumatology department

Strasbourg, 67098, France

Location

Toulouse Hospital, Dermatology department

Toulouse, 31060, France

Location

Related Publications (9)

• Johnson MR, Verstovsek S, Jorgensen JL, Manshouri T, Luthra R, Jones DM, Bueso-Ramos CE, Medeiros LJ, Huh YO. Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow. Mod Pathol. 2009 Jan;22(1):50-7. doi: 10.1038/modpathol.2008.141. Epub 2008 Sep 19.

  PMID: 19116630 BACKGROUND

• Theoharides TC, Valent P, Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med. 2015 Jul 9;373(2):163-72. doi: 10.1056/NEJMra1409760. No abstract available.

  PMID: 26154789 BACKGROUND

• Frenzel L, Hermine O. Mast cells and inflammation. Joint Bone Spine. 2013 Mar;80(2):141-5. doi: 10.1016/j.jbspin.2012.08.013. Epub 2012 Oct 30.

  PMID: 23116710 BACKGROUND

• Rabenhorst A, Christopeit B, Leja S, Gerbaulet A, Kleiner S, Forster A, Raap U, Wickenhauser C, Hartmann K. Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol. 2013 Nov;132(5):1234-1237.e7. doi: 10.1016/j.jaci.2013.06.019. Epub 2013 Jul 31. No abstract available.

  PMID: 23910691 BACKGROUND

• Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Frances C. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010 Oct;69(10):1838-41. doi: 10.1136/ard.2009.124511. Epub 2010 Jun 22.

  PMID: 20570833 BACKGROUND

• van der Veer E, Arends S, van der Hoek S, Versluijs JB, de Monchy JGR, Oude Elberink JNG, van Doormaal JJ. Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis. J Allergy Clin Immunol. 2014 Dec;134(6):1413-1421. doi: 10.1016/j.jaci.2014.05.003. Epub 2014 Jun 27.

  PMID: 24985401 BACKGROUND

• Rossini M, Zanotti R, Viapiana O, Tripi G, Idolazzi L, Biondan M, Orsolini G, Bonadonna P, Adami S, Gatti D. Zoledronic acid in osteoporosis secondary to mastocytosis. Am J Med. 2014 Nov;127(11):1127.e1-1127.e4. doi: 10.1016/j.amjmed.2014.06.015. Epub 2014 Jun 20.

  PMID: 24954632 BACKGROUND

• Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, McKoy JM, Omar I, Belknap SM, Garg V, Hahr AJ, Samaras AT, Fisher MJ, West DP, Langman CB, Stern PH. Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. J Bone Joint Surg Am. 2013 Feb 20;95(4):297-307. doi: 10.2106/JBJS.K.01181.

  PMID: 23426763 BACKGROUND

• Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.

  PMID: 19671655 BACKGROUND

MeSH Terms

Conditions

Osteoporosis; Mastocytosis, Systemic

Interventions

Denosumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Olivier Hermine, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

• Laurent FRENZEL, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 17, 2018
• Study Start: March 5, 2018
• Primary Completion: March 11, 2024
• Study Completion: March 11, 2024
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)