A study for the assessment of therapeutic efficacy of a drug (Denosumab) that will be administered in adult patients with mild symptoms of LCH.

Phase 1

• Conditions: angerhans Cell Histiocytosis (LCH) is a rare disease of unknown etiology with variable clinical course exhibiting both neoplastic and inflammatory features. It is characterized by the accumulation and/or proliferation of specific dendritic cells resembling normal epidermal Langerhans cells.; MedDRA version: 21.1 Level: PT Classification code 10069698 Term: Langerhans' cell histiocytosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2016-003300-31-GR
• Lead Sponsor: Hellenic Society for the Study of Bone Metabolism

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-28
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1)Adults (>18 years of age)

2)Definitive diagnosis of LCH [1] [Based on clinic-pathological evidence with microscopic examination and at least one of the following immunological staining: Langerin (CD 207) positivity, CD1a positivity, Presence of Birbeck granules on electronic microscopy]

3)Mild symptoms needing first line systemic therapy for LCH because of:

-single system disease with multifocal lesions;

-single system disease with special site” lesions (vertebral lesions with intraspinal extension, craniofacial bone lesions with soft tissue extension);

-multi-system disease without involvement of risk organs (hematopoietic system, spleen, liver, tumorous CNS.).

4) Have signed the informed consent form (consent should be taken before any study-specific procedure is performed).

5) A patient should undergo a PET-CT imaging test, in order for him to be deemed suitable for the study. The initial PET-CT either may have been carried out, within 3 months prior to visit 1, regardless of the diagnostic center or the type of the device, which has been used for, or may take place in the context of visit 2, at the diagnostic center(s) specialized on Nuclear Medicine, which have been partnered with the Sponsor. Whichever is the case, the initial PET-CT report should be legible and accurate, so that to be assessed by the qualified physician, responsible for the PET-CT test at the partnered diagnostic center(s).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Symptomatic multi system LCH - no risk organs involved.
2. Multi-system LCH (with or without symptoms) - risk organs involved.
3. Isolated pulmonary LCH disease
4. Previous administration of denosumab from clinical trials or other use (e.g. commercial use).
5. Current participation in another clinical trial or having received any investigational product within the last 3 months.
6. Impaired renal function as determined by an estimated glomerular filtration rate eGFR of = 30 mL/min/1,73m2 [using the Chronic Kidney Disease-Epidemiology, (CKD-EPI) formula].
7. Patients that have received oral bisphosphonates within 6 months of study enrollment or intravenous bisphosphonates, fluoride and strontium ranelate within 1 year of study enrollment.
8. Treatment with immune suppressive agents within 4 weeks from baseline evaluation.
9. Patients with severe impairment of clinical condition including: severely impaired pulmonary function (for example TLC<60%, FEV1<30%, DLCO<30%, PaO2<55 mmHg), long term oxygen therapy or cor pulmonale.
10. Known to have a liver failure or chronic hepatic disease e.g. cirrhosis, chronic hepatitis; or elevated transaminases defined as ALT and/or AST > 2 fold the upper limit of normal laboratory range.
11. Heart failure (NYHA above 2).
12. Patients with life expectancy of less than one year.
13. Female subjects of childbearing potential who refuse to use a reliable contraceptive method throughout the study, defined as use of 2 highly effective forms of contraception and continuation of use for 7 months after last administration of study drug. Birth control methods that can achieve a failure rate of less than 1% per year, when used consistently and correctly, are considered as highly effective.
Highly effective methods of birth control include:
•Combined (estrogen and progestogen) hormonal methods (pills, vaginal ring, or skin patch)
•Single hormonal methods (progesterone) to stop release of the egg from the ovary (pills, shots/injections, or implants placed under the skin by a healthcare provider)
•Intrauterine device (IUD)
•Intrauterine hormonal-releasing system (IUS)
•Surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion
•A male partner has had a vasectomy and testing shows there is no sperm in the semen
•Sexual abstinence (not having sex)
14. Pregnancy, planning a pregnancy or currently lactating
15. Severe concurrent illness which in the investigator’s opinion may confound patient evaluation, e.g. malignancy (except basal cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years.
16. Known alcohol or drug abuse.
17. PTH, PTH derivatives, teriparatide, odanacatib, anabolic steroids, testosterone, glucocorticosteroids (> 5 mg/day of prednisone equivalent for > 10 days), systemic hormone-replacement therapy, selective estrogen receptor modulators (SERMs), raloxifene, tibolone, calcitonin use within the last 6 weeks.
18. Evidence of hyper- or hypothyroidism; patients with an abnormal TSH level on thyroid treatment (patients on stable thyroid treatment with a nor

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified