Senolytics to Improve Osteoporosis therapy: A randomised controlled clinical trial The SENIOR Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2022-08-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

to investigate the efficacy and safety of dasatinib plus quercetin or nicotinamide riboside on bone resorption in patients with low bone mass

Conditions and MedDRA coding

Osteoporosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Men and women (menopause > 5 years and FSH and LH in the postmenopausal range) aged 60-90 years with a T-score < -1 at the total hip/femoral neck, or lumbar spine (increased risk for developing osteoporosis T-score -1to -2.5, or osteoporosis T-score <-2.5).
2. Ability to provide informed consent

Exclusion criteria 20

1. DXA of hip or spine not possible e.g., due to a prosthesis
2. T-score <-2.5 at the hip or lumbar spine. These individuals may be included if they prefer to participate or are not candidates for conventional osteoporosis therapies
3. Inability to provide fasting blood samples
4. Primary hyperparathyroidism
5. Vitamin D deficiency (<50 nM) (re-test after substitution acceptable)
6. Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <20) or liver function (baseline phosphatase higher than twice upper limit, rheumatism, celiac disease/malabsorption, hypogonadism, severe COPD, hypopituitarism, Cushing's disease, uncontrolled diabetes (HbA1c > 58 mmol/mol).
7. Antiresorptive or bone anabolic drugs for the last 3 years
8. Concomitant treatments known to influence bone metabolism e.g., glucocorticoids (systemic treatments), anabolic steroids, etc.
9. Subjects taking the following other drugs if they cannot be held for at least 2 days before and during administration of dasatinib+quercetin: digoxin, lithium, all statins, repaglidine, bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate, corticosteroids, eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacrolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, warfarin, heparin, clopidogrel, celecoxib, desipramine, thioridazine, venlafaxine, tizanidine, atomoxetine, voriconazole, citalopram, diazepam, escitalopram, propranolol, clozapine, cyclobenzaprine, mexiletine, olanzapine, ondansetron
10. Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus). If antifungals are necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic.
11. Subjects taking proton pump inhibitors and unwilling to discontinue therapy for two days before and during the study drug dosing periods.
12. Anti-arrhythmic medications known to cause QTc prolongation
13. Tyrosine kinase inhibitor therapy
14. Subjects with an abnormal Complete Blood Count (clinically insignificant changes would be acceptable based on the judgement of the investigators)
15. Subjects on antiplatelet agents (Clopidogrel; Dipyridamole + ASA; ASA, Ticagrelor; Prasugrel; Ticlopidine or other) who are unable or unwilling to reduce or hold therapy prior to and during the study drug dosing periods and collection of bone biopsies. Subjects may continue their previous regimen between study drug dosing periods.
16. Known allergy to dasatinib, quercetin, or NR
17. Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin, erythromycin), antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir)
18. Presence of any condition the Investigator believes would place the subject at risk or would preclude the subject from successfully completing all aspects of the trial e.g., heart failure, malignancy etc.
19. QTc >470 msec
20. Inability to take oral medication

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in circulating marker of bone resorption (CTX) at 20 weeks.

Secondary endpoints 2

1. Bone resorption marker tartrate resistant acid phosphatase (TRAcP) at 20 weeks.
2. Bone formation markers (PINP, osteocalcin, and bone alkaline phosphatase) at 20 weeks.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Shakespeare Jeromdesella

Public contact point

Organisation

Odense University Hospital

Contact name

Shakespeare Jeromdesella

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications