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]

Trial duration

16 Aug 2023 → 24 Apr 2026

Decision date (initial)

2023-03-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-502076-23-00

ClinicalTrials.gov

NCT06018467

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

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

osteopenia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Men and women (menopause > 5 years and FSH and LH in the postmenopausal range) aged 60-90 years
2. Increased fracture risk according to WHO 10 years absolute Fracture Risk Assessment Tool (FRAX). Osteopenia (ICD10 DM858A) based on a T-score ≤ -1 to -2.5 at the total hip/femoral neck, or lumbar spine, with or without a fragility fracture at any time (excluding hip and vertebral fractures within the last 2 years) (FRAX ranging from 7-70), or Osteoporosis (ICD10 DM819) based on a T-score between ≥-3 and ≤ -2.5, which includes candidates suitable for conventional osteoporosis therapies, but who prefer to participate in the trial, despite being candidates for conventional osteoporosis therapy, or candidates which cannot be treated with conventional therapies due to contraindications.
3. Ability to provide informed consent

Exclusion criteria 21

1. DXA of hip or spine not possible e.g., due to a prosthesis
2. QTc >470 msec
3. Inability to take oral medication
4. Inability to provide fasting blood samples
5. Primary hyperparathyroidism
6. Vitamin D deficiency (<50 nM) (re-test after substitution acceptable)
7. Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, chronic kidney disease defined as eGFR <30 or liver dysfunction, rheumatism, celiac disease/malabsorption, hypogonadism, severe COPD, hypopituitarism, Cushing's disease, uncontrolled diabetes (HbA1c > 58 mmol/mol)
8. Antiresorptive or bone anabolic drugs for the last 2 years (5 years if treated with zoledronic acid)
9. Concomitant treatments known to influence bone metabolism e.g., glucocorticoids (systemic treatments), anabolic steroids, etc.
10. Subjects taking the following other drugs if they cannot be held for at least 2 days before and during administration of D+Q: 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
11. 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.
12. Subjects taking proton pump inhibitors and unwilling to discontinue therapy for two days before and during the study drug dosing periods.
13. The study will exclude subjects with inability to speak and understand Danish and with inability to cooperate.
14. Anti-arrhythmic medications known to cause QTc prolongation
15. Tyrosine kinase inhibitor therapy
16. Subjects with an abnormal Complete Blood Count (clinically insignificant changes would be acceptable based on the judgement of the investigators)
17. 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.
18. Known allergy to dasatinib, quercetin, or nicotinamide riboside
19. Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin, erythromycin), antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir)
20. 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.
21. BMI ≥ 40

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in circulating marker of bone resorption (CTX) at 21 weeks.

Secondary endpoints 2

1. Bone resorption marker tartrate resistant acid phosphatase (TRAcP) at 21 weeks.
2. Bone formation markers (PINP, osteocalcin, and bone alkaline phosphatase) at 21 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

KMEB lab

Public contact point

Organisation

Odense University Hospital

Contact name

KMEB lab

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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