OsteoporosisPhase 3DenosuMastNCT03401060
Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis
A Phase 3 study testing Denosumab in people with Osteoporosis and Systemic Mastocytosis, run by Assistance Publique - Hôpitaux de Paris at 11 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoporosis, Systemic Mastocytosis
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 11 sitesFrance
- Study dates
- 5 Mar 2018to 11 Mar 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
France11 sites
Jean Minjoz Hospital, Dermatology department
Besançon, 25030
Caen Hospital, Clinical haematology department
Caen, 14033
Estaing Hospital, Cellular therapy and clinical haematology department
Clermont-Ferrand, 63100
Lille CHRU Hospital, Internal medicine and clinical immunology department
Lille, 59037
La Timone Hospital, Dermatology and cutaneous oncology department
Marseille, 13385
Lapeyronie Hospital, Rheumatology and Immunology department
Montpellier, 34295
La Pitié-Salpêtrière Hospital, Internal medicine and clinical immunology department
Paris, 75013
Cochin Hospital, Rheumatology department
Paris, 75014
Necker Hospital, Adult haematology department
Paris, 75015
Strasbourg Hospital, Rheumatology department
Strasbourg, 67098
Toulouse Hospital, Dermatology department
Toulouse, 31060
About this study
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.
Read the detailed description
Systemic mastocytosis (SM) represents a heterogenous group of disease characterized by abnormal proliferation of mast cells caused by activating mutations in c-Kit receptor; a tyrosine kinase family receptor present in mast cell that control cell proliferation. Prevalence of SM is estimated to 1/20 000 person. According to the World Health Organization (WHO) criteria (Johnson et al, 2009), SM can be separated into two different groups : indolent SM and aggressive SM.
Aggressive SM are defined by a poor prognostic disease either because of an important mast cell tumor mass as sarcoma mastocytosis or mast cell leukemia, or due to an association with an other myeloid hemopathy as myelodysplasic/myeloproliferative syndrome.
Indolent SM are the most common cases with a very good prognostic similar to general population. Symptoms related to mast cell proliferation in indolent SM are very various (Theoharides et al., 2015) and could be divided into 2 entities : those related to mast cell proliferation in tissue as the urticaria pigmentosa and those related to the mast cell degranulation.
There are many clinical relevant mediators released by mast cells after activation that could have putative effects on different systems as cardiovascular, cutaneous, neurologic, digestive, systemic, respiratory and musculoskeletal (Frenzel et al., 2013). Tryptase, histamine, prostaglandin, interleukine-6 and Tumor Necrosis Factor (TNF)-α are the most common and ubiquitous mediators released by mast cells but there are also some specific mediator targeting an organ as RANKL ; expression of RANKL by mast cells directly control regulation of osteoclast activity and is involved in osteoporosis associated to SM (Rabenhorst et al., 2013).
In systemic mastocytoses, bone lesions are found in about half of patients. A third have osteoporosis defined as a lumbar spine or hip bone T score of -2,5 Standard Deviation (SD) or less. In most cases, osteoporosis was complicated at least by one vertebral fracture with pain and functional disorders (Barete et al, 2010). The median time to fragility fracture after mastocytoses diagnosis is up to 5 years, even in very young population usually considering as low risk of fracture in non mastocytoses associated osteoporosis (Van de Veer et al., 2014)
By default, these patients are generally treated with bisphosphonate per os or intravenously with some efficiency on bone mineral density gain and bone turnover marker decrease (Rossini et al, 2014). However, no study with bisphosphonate in SM has showed durable prevention of new bone events and there are no randomized studies that proved their efficacy in systemic mastocytosis. Moreover, these drugs are not well tolerated in SM wether per os due to worsening of digestive symptoms by mast cells activation, or intravenously with an important number of acute phase characterized by some systemic symptoms as fever ; really experiences with intravenous biphosphonate but very increased in SM. Additional, the use of a bisphosphonate ask the question of the residual long-term effect of this drug that may be several years or even decades with a significant risk of atypical fracture secondary to a adynamic bone remodeling (Edwards et al. , 2013) and the long-term presence of crystals of bisphosphonate in the skeleton, particularly worrying in women of childbearing age. In postmenopausal osteoporosis, importance of residual long-term effect is weighted with advanced median age of patient. The fact that mostly patients with a systemic mastocytosis are young people led to restrict the use of bisphosphonate due to those effects.
Among different treatment available in post menopausal osteoporosis, the use of an anti-RANKL antibody, denosumab, in SM associated osteoporosis could be interesting. First, denosumab has already shown significant efficacy in the treatment of postmenopausal osteoporosis in women (Cummings et al , 2009). Second, this treatment is proposed every 6 months by a subcutaneous injection with very few side effects and half-life drug is shorter than biphosphonate with probably low residual long-time effect. Third, as mast cells expressed mainly RANKL with a direct role on bone turnover in SM. The use of a specific drug seems to be obvious and attractive.
- Conditions
- Osteoporosis, Systemic Mastocytosis
- Being tested
- Denosumab, Placebo
- Keywords
- Systemic mastocytosis, Osteoporosis, Bone mineral density (BMD), Denosumab, RANKL
- Medical subject headings
- Osteoporosis, Mastocytosis, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called XGeva®
Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections
PlaceboDrug
Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections
| Study group | Role | What they receive |
|---|---|---|
| Experimental medication 1 | Experimental | Denosumab 60 mg subcutaneously injection with prefilled syringe Receives: Drug: Denosumab |
| Experimental medication 2 | Placebo comparator | NaCl 0.9%, 20ml phial, solution for injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of the lumbar spine bone mineral density (BMD)
Dual energy x-ray absorptiometry at lumbar spine (L2-L4)
Measured: 3 years
Secondary outcomes (7)
Occurrence of a low energy vertebral fracture and non vertebral fracture
Lateral and front lumbar x-ray
Measured: Baseline, 1 year, 2 years and 3 years
BMD at the total left hip
Dual energy x-ray absorptiometry at lumbar spine (L2-L4)
Measured: Baseline, 3 years
BMD at lumbar spine and the total left hip
Dual energy x-ray absorptiometry at left femoral neck and total left hip
Measured: Baseline, 1 year, 2 years
Biological assays with bone turnover marker of resorption and tryptase levels to assess mastocytosis activity
Withdrawal of 45 ml of blood
Measured: Baseline, then every 6 months in 3 years
Number of serious adverse events to evaluate drug tolerance
- Biological assessment: complete blood count, creatinemia, electrolytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, c-reactive protein (CRP), phosphocalcic analyses with calcemia, phosphoremia, parathormone, vitamin D (25-OH-D), β-Human Chorionic Gonadotropin (HCG) (if needed)
- Clinical assessment: blood pressure, pulse, weight, height, PS, temperature
Measured: Every 6 months in 3 years
Number of non-serious adverse events to evaluate drug tolerance
- Biological assessment: complete blood count, creatinemia, electrolytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, c-reactive protein (CRP), phosphocalcic analyses with calcemia, phosphoremia, parathormone, vitamin D (25-OH-D), β-Human Chorionic Gonadotropin (HCG) (if needed)
- Clinical assessment: blood pressure, pulse, weight, height, PS, temperature
Measured: Every 6 months in 3 years
Annual variation of BMD in placebo group and number of low energy fracture compared to historical postmenopausal data
Dual energy x-ray absorptiometry at lumbar spine (L2-L4), left femoral neck and total left hip
Measured: Baseline, 1 year, 2 years, 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start5 Mar 2018
- Primary completion11 Mar 2024
- Study completion11 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- CEREMAST, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Olivier Hermine, MD, Study director, Assistance Publique - Hôpitaux de ParisLaurent FRENZEL, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401060
- Sponsor's protocol ID
- P150918J
- Other IDs
- 2016-000596-25, 2016
- Acronym
- DenosuMast
- Status last verified
- Mar 2026
- First submitted
- 4 Jan 2018
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 19116630Theoharides 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.
PubMed 26154789Frenzel 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.
PubMed 23116710Rabenhorst 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.
PubMed 23910691Barete 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.
PubMed 20570833van 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.
PubMed 24985401Rossini 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.
PubMed 24954632Edwards 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.
PubMed 23426763Cummings 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.
PubMed 19671655
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis
- ClinicalTrials.gov ID
- NCT03401060
- Acronym / sponsor ID
- DenosuMast / P150918J
- Conditions
- Osteoporosis, Systemic Mastocytosis
- Keywords
- Systemic mastocytosis, Osteoporosis, Bone mineral density (BMD), Denosumab, RANKL
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- CEREMAST, URC-CIC Paris Descartes Necker Cochin
- Study start
- 5 Mar 2018 (actual)
- Primary completion
- 11 Mar 2024 (actual)
- Study completion
- 11 Mar 2024 (actual)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Systemic mastocytosis (SM) represents a heterogenous group of disease characterized by abnormal proliferation of mast cells caused by activating mutations in c-Kit receptor; a tyrosine kinase family receptor present in mast cell that control cell proliferation. Prevalence of SM is estimated to 1/20 000 person. According to the World Health Organization (WHO) criteria (Johnson et al, 2009), SM can be separated into two different groups : indolent SM and aggressive SM.
Aggressive SM are defined by a poor prognostic disease either because of an important mast cell tumor mass as sarcoma mastocytosis or mast cell leukemia, or due to an association with an other myeloid hemopathy as myelodysplasic/myeloproliferative syndrome.
Indolent SM are the most common cases with a very good prognostic similar to general population. Symptoms related to mast cell proliferation in indolent SM are very various (Theoharides et al., 2015) and could be divided into 2 entities : those related to mast cell proliferation in tissue as the urticaria pigmentosa and those related to the mast cell degranulation.
There are many clinical relevant mediators released by mast cells after activation that could have putative effects on different systems as cardiovascular, cutaneous, neurologic, digestive, systemic, respiratory and musculoskeletal (Frenzel et al., 2013). Tryptase, histamine, prostaglandin, interleukine-6 and Tumor Necrosis Factor (TNF)-α are the most common and ubiquitous mediators released by mast cells but there are also some specific mediator targeting an organ as RANKL ; expression of RANKL by mast cells directly control regulation of osteoclast activity and is involved in osteoporosis associated to SM (Rabenhorst et al., 2013).
In systemic mastocytoses, bone lesions are found in about half of patients. A third have osteoporosis defined as a lumbar spine or hip bone T score of -2,5 Standard Deviation (SD) or less. In most cases, osteoporosis was complicated at least by one vertebral fracture with pain and functional disorders (Barete et al, 2010). The median time to fragility fracture after mastocytoses diagnosis is up to 5 years, even in very young population usually considering as low risk of fracture in non mastocytoses associated osteoporosis (Van de Veer et al., 2014)
By default, these patients are generally treated with bisphosphonate per os or intravenously with some efficiency on bone mineral density gain and bone turnover marker decrease (Rossini et al, 2014). However, no study with bisphosphonate in SM has showed durable prevention of new bone events and there are no randomized studies that proved their efficacy in systemic mastocytosis. Moreover, these drugs are not well tolerated in SM wether per os due to worsening of digestive symptoms by mast cells activation, or intravenously with an important number of acute phase characterized by some systemic symptoms as fever ; really experiences with intravenous biphosphonate but very increased in SM. Additional, the use of a bisphosphonate ask the question of the residual long-term effect of this drug that may be several years or even decades with a significant risk of atypical fracture secondary to a adynamic bone remodeling (Edwards et al. , 2013) and the long-term presence of crystals of bisphosphonate in the skeleton, particularly worrying in women of childbearing age. In postmenopausal osteoporosis, importance of residual long-term effect is weighted with advanced median age of patient. The fact that mostly patients with a systemic mastocytosis are young people led to restrict the use of bisphosphonate due to those effects.
Among different treatment available in post menopausal osteoporosis, the use of an anti-RANKL antibody, denosumab, in SM associated osteoporosis could be interesting. First, denosumab has already shown significant efficacy in the treatment of postmenopausal osteoporosis in women (Cummings et al , 2009). Second, this treatment is proposed every 6 months by a subcutaneous injection with very few side effects and half-life drug is shorter than biphosphonate with probably low residual long-time effect. Third, as mast cells expressed mainly RANKL with a direct role on bone turnover in SM. The use of a specific drug seems to be obvious and attractive.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental medication 1 | Experimental | Drug: DenosumabDenosumab 60 mg subcutaneously injection with prefilled syringe |
| Experimental medication 2 | Placebo comparator | Drug: PlaceboNaCl 0.9%, 20ml phial, solution for injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- (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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: XGeva®Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections | Drug | Experimental medication 1 |
| PlaceboEach subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections | Drug | Experimental medication 2 |
Primary outcome
Analysis of the lumbar spine bone mineral density (BMD)
Time frame: 3 years
Dual energy x-ray absorptiometry at lumbar spine (L2-L4)
7 secondary outcomes
Occurrence of a low energy vertebral fracture and non vertebral fracture
Time frame: Baseline, 1 year, 2 years and 3 years
BMD at the total left hip
Time frame: Baseline, 3 years
BMD at lumbar spine and the total left hip
Time frame: Baseline, 1 year, 2 years
Biological assays with bone turnover marker of resorption and tryptase levels to assess mastocytosis activity
Time frame: Baseline, then every 6 months in 3 years
Number of serious adverse events to evaluate drug tolerance
Time frame: Every 6 months in 3 years
Number of non-serious adverse events to evaluate drug tolerance
Time frame: Every 6 months in 3 years
Annual variation of BMD in placebo group and number of low energy fracture compared to historical postmenopausal data
Time frame: Baseline, 1 year, 2 years, 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Background: PubMed 19116630Johnson 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.
- Background: PubMed 26154789Theoharides 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.
- Background: PubMed 23116710Frenzel 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.
- Background: PubMed 23910691Rabenhorst 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.
- Background: PubMed 20570833Barete 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.
- Background: PubMed 24985401van 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.
- Background: PubMed 24954632Rossini 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.
- Background: PubMed 23426763Edwards 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.
- Background: PubMed 19671655Cummings 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Hermine, MD study director
Assistance Publique - Hôpitaux de Paris
Laurent FRENZEL, MD principal investigator
Assistance Publique - Hôpitaux de Paris
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Denosumab in people with Osteoporosis and Systemic Mastocytosis, run by Assistance Publique - Hôpitaux de Paris at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analysis of the lumbar spine bone mineral density (BMD) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03401060, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.