Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruitment pending
Participants planned
120
Countries
1
Sites
1
General healthy elderly with stable medical conditions
To investigate if everolimus (rapamycin analog) prevents age-related bone loss by enhancing bone formation and improving muscle functions and reducing the burden of biological mechanisms of aging in elderly persons.
Key facts
- Sponsor
- Odense University Hospital
- Participant type
- Healthy volunteers
- Age range
- 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05]
- Decision date (initial)
- 2024-03-14
- 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 if everolimus (rapamycin analog) prevents age-related bone loss by enhancing bone formation and improving muscle functions and reducing the burden of biological mechanisms of aging in elderly persons.
Conditions and MedDRA coding
General healthy elderly with stable medical conditions
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Men and women aged 65-85 years old, any ethnicity
- Be in relatively good general health,(with only well-managed chronic diseases (hypertension, coronary artery disease, etc.), clinically stable
- Participants without health conditions that could limit walking (for instance recent injury)
Exclusion criteria 19
- Diabetes type 1 and 2
- Heart failure similar to NYHA Class IV
- Primary hyperparathyroidism
- Known vitamin D deficiency (<25 nM) (re-test after substitution acceptable)
- Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <20) or liver function (baseline phosphatase higher than twice upper limit (105 U/L)), active rheumatic diseases, celiac disease, severe chronic obstructive lung disease (COPD), hypopituitarism, or Cushing’s disease.
- Previous use of bone antiresorptive or bone anabolic drugs within the last 5 years
- Use of anabolic steroids in the previous year
- Inability to give informed consent
- Treatment with drugs known to affect cytochrome P450 3A due to its role in rapamycin metabolism
- History of coagulopathy or medical condition requiring long-term anticoagulation
- Anemia – Hg < 9.0 g/dl, Leukopenia – white blood cells (WBC) < 3,500/mm3 , Neutropenia absolute neutrophil count < 2,000/mm3 , or Platelet count – platelet count < 125,000/mm3
- Patients with impaired wound healing or history of a chronic open wound
- Scheduled for immunsuppresant therapy for transplant or scheduled to undergo chemotherapy or any other treatment for malignancy
- Untreated dyslipidemia with LDL-c > 4.9 mmol/L and family history of dyslipidemia, Total cholesterol > 9.1 mmol/L, or triglycerides > 9.9 mmol/L
- Any form of clinically relevant primary or secondary immune dysfunction or deficiency
- Unstable ischemic heart disease
- Bone mineral density (BMD) measured by DXA scanning with T-score <-3
- Known allergy to rapamycin or rapalogs
- The study will exclude participants with inability to speak and understand Danish and with inability to cooperate
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Changes in serum bone formation marker P1NP
Secondary endpoints 5
- Changes in serum bone resorption marker CTX
- Changes in areal BMD at the lumbar spine, total hip and femoral neck measured by DXA scanning
- Changes in volumetric BMD, bone microstructures and estimated strength at distal tibia and radius (HRpQT)
- Changes in muscle function, power and strength for upper and lower extremities will be assessed using a standard hydraulic hand dynamometer, the 30-second sit-to-stand test (RSS), respectively and gait speed.
- Changes in health-related quality of life assessment (SF-12 questionnaire)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD400622 · Product
- Active substance
- Everolimus
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 0.7 mg milligram(s)
- Max total dose
- 80 mg milligram(s)
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EG02 — -
- Marketing authorisation
- EU/1/09/538/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The tablet comes in a capsule and will be blinded for the participants
Placebo 1
SUB21402 · Substance
- Active substance
- Placebo
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 0.7
- Max total dose
- 80
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 1
PRD2872958 · Product
- Active substance
- Tetracycline Hydrochloride Bp
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 500 mg milligram(s)
- Max total dose
- 3000 mg milligram(s)
- Max treatment duration
- 20 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01AA07 — TETRACYCLINE
- Marketing authorisation
- PL 33414/0110
- MA holder
- CHELONIA HEALTHCARE LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
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
- Moustapha Kassem
Public contact point
- Organisation
- Odense University Hospital
- Contact name
- Moustapha Kassem
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Odense University Hospital ORG-100007716
|
Odense C, Denmark | On site monitoring, E-data capture, Code 8 |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Authorised, recruitment pending | 120 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | Recruitment arrangements | 1.1 |
| Recruitment arrangements (for publication) | Recruitment material description | 2.0 |
| Subject information and informed consent form (for publication) | Dine rettigheder som forsgsperson i forsg med medicin | 1 |
| Subject information and informed consent form (for publication) | ICF adults | 1 |
| Subject information and informed consent form (for publication) | ICF adults bonemarrow aspirate and biopsy | 1.1 |
| Subject information and informed consent form (for publication) | ICF data rights | 1 |
| Subject information and informed consent form (for publication) | ICF unused material biobank | 1 |
| Subject information and informed consent form (for publication) | ICF unused material biobank bone samples | 1.1 |
| Subject information and informed consent form (for publication) | Recruitment material powerpoint | 2.0 |
| Subject information and informed consent form (for publication) | RENOVATE Visual Trial Design Overview | 1 |
| Subject information and informed consent form (for publication) | RENOVATE Visual Trial Design Overview | 2.0 |
| Subject information and informed consent form (for publication) | SF-12 questionnaire | 1 |
| Subject information and informed consent form (for publication) | SIS | 2.0 |
| Subject information and informed consent form (for publication) | SIS bone marrow aspirations and biopsies | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC Afinitor | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-12-20 | Denmark | Acceptable 2024-03-14
|
2024-03-14 |
| 2 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-03-05 | Denmark | Acceptable | 2026-03-24 |