The effect of oral Semaglutide on bone turnover in patients with T2D: a randomized placebo-controlled clinical trial (SOBER II)

2023-505959-45-00 Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 31 May 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 64
Countries 1
Sites 1

Type 2 diabetes

The aim of this trial is to investigate if semaglutide a long-acting GLP-1RA, improves bone formation and strength in men and women with type 2 diabetes and either normal or low bone mass.

Key facts

Sponsor
Odense University Hospital
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nutritional and Metabolic Diseases [C18]
Trial duration
31 May 2024 → ongoing
Decision date (initial)
2023-09-07
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Novo Nordisk Foundation · Novo Nordisk A/S

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The aim of this trial is to investigate if semaglutide a long-acting GLP-1RA, improves bone formation and strength in men and women with type 2 diabetes and either normal or low bone mass.

Conditions and MedDRA coding

Type 2 diabetes

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Study design SOBER II
This is a randomized, placebo-controlled, double-blinded study of the effects of 52 weeks of treatment with once daily oral GLP-1Ra semaglutide or matching placebo on bone formation. Semaglutide will be dosed as follows: Weeks 1-4: 3 mg of oral semaglutide or placebo once daily. Weeks 5-52: 7 mg of semaglutide or placebo once daily as maintenance dose. Dose may be increased to 14 mg of semaglutide or placebo once daily as maintenance dose after 2 months if HbA1c is out of range.
 Randomised Controlled Double [{"id":155395,"code":3,"name":"Monitor"},{"id":155394,"code":1,"name":"Subject"},{"id":155391,"code":2,"name":"Investigator"},{"id":155393,"code":5,"name":"Carer"},{"id":155392,"code":4,"name":"Analyst"}] Semaglutide: Oral semaglutide
Placebo: Oral placebo

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. Type 2 diabetes and glycosylated haemoglobin (HbA1C) of 44-91 mmol/mol (6.2-10.5%) and
  2. T-score </=+1 in hip or lower back, assessed by DXA scan and / or
  3. Low-energy fracture within the last 3 years

Exclusion criteria 18

  1. T-score <-2.5 in hip or lower back, assessed by DXA scan, although these individuals may be included if they are not candidates for conventional osteoporosis therapy, e.g., due to allergies and renal impairment, or if they prefer to participate in the trial.
  2. Type 1 diabetes mellitus
  3. Severe NPDR (non-proliferative diabetic retinopathy) or PDR (proliferative diabetic retinopathy) assessed within the last year. If a recent assessment is unavailable, a new retinal photo test will be performed.
  4. Congestive heart failure (NYHA Class IV)
  5. Primary hyperparathyroidism
  6. Vitamin D deficiency (<25 nM) (re-test after substitution acceptable)
  7. Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <30) or liver dysfunction (baseline phosphatase higher than twice upper limit (105 U/L)), rheumatism, celiac disease, hypogonadism, severe COPD, hypopituitarism, Cushing's disease
  8. Clinically significant concomitant diseases or disorders (e.g., cancer) or clinically significant abnormal values in laboratory screening tests, including increased Choriogonadotropin (hCG) in women.
  9. History of gastrointestinal surgery (except uncomplicated surgical procedures such as hernia surgery and appendectomy)
  10. Antiresorptive or bone anabolic drugs for the last 12 months
  11. Use of anabolic steroids in the previous year
  12. Use of GLP-1Ras within 90 days
  13. Stable therapy with DPP4 inhibitors (unless the patient is willing to discontinue the treatment)
  14. History of pancreatitis
  15. Allergy or hypersensitivity to the active substance or to any of the ingredients
  16. Inability to give informed consent
  17. Previous bariatric surgery
  18. BMI <20 kg/m2 or BMI>37 kg/m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Percentage change in bone formation marker procollagen type 1 N-terminal propeptide (P1NP) after 52 weeks.

Secondary endpoints 10

  1. Change in bone strength, assessed by microindentation
  2. Change in bone formation rate, based on dynamic histomorphometry of bone tissue
  3. Change in bone degradation markers Collagen I, cross-linked C-terminal telopeptide (CTX)
  4. Change in bone formation markers osteocalcin and bone alkaline phosphatase
  5. Change in bone mineral density, assessed by DXA scan
  6. Change in trabecular and cortical volumetric bone density and estimated strength (finite element analysis), assessed using second generation high resolution peripheral quantitative CT
  7. Change in fat and lean tissue distribution, assessed by DXA
  8. Change in BMI
  9. Change in HbA1c
  10. Change in physical activity, based on analysis of International Physical Activity Questionnaire Short Form (IPAQ-SF).

Investigational products

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

Test 3

Semaglutide

SUB32188 · Substance

Active substance
Semaglutide
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
7 mg milligram(s)
Max total dose
2352 mg milligram(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Semaglutide

SUB32188 · Substance

Active substance
Semaglutide
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
3 mg milligram(s)
Max total dose
1095 mg milligram(s)
Max treatment duration
52 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Semaglutide

SUB32188 · Substance

Active substance
Semaglutide
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
14 mg milligram(s)
Max total dose
4704 mg milligram(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo

SUB21402 · Substance

Active substance
Placebo
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
0 mg milligram(s)
Max total dose
0 mg milligram(s)
Max treatment duration
52 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Placebo for semaglutide. the clinic variant of placebo are produced with the same composition (despite no active substance) as semaglutide of novo nordisk a/s. both oral semaglutide and placebo are produced with the tablet debossment ‘m8’ in 7 tablet blister packs with no colour on forming foil and no print on lid foil.

Auxiliary 1

Tetracycline 250 mg Tablets

PRD427031 · Product

Active substance
Tetracycline Hydrochloride
Pharmaceutical form
COATED TABLET
Route of administration
ORAL
Max daily dose
500 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
6 Day(s)
Authorisation status
Authorised
ATC code
J01AA07 — TETRACYCLINE
Marketing authorisation
PL 36722/0018
MA holder
SPECIAL CONCEPT DEVELOPMENT (UK) LTD
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

51 Total trials 30 Recruiting 11 Ended
Academic / Non-commercial
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
Julie Bjerrelund

Public contact point

Organisation
Odense University Hospital
Contact name
Julie Bjerrelund

Third parties 1

OrganisationCity, countryDuties
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

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruiting 64 1
Rest of world — 0 —

Investigational sites

Denmark

1 site · Ongoing, recruiting
Odense University Hospital
Department of Endocrinology / Steno Diabetes Centre Odense, J B Winsloews Vej 4, 5000, Odense C

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2024-05-31 2024-05-31

Results and documents

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

Documents 22 files

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

TypeTitleVersion
Protocol (for publication) IPAQ kort sprgeskema 1
Protocol (for publication) Protocol 2023-505959-45-00 2.7
Recruitment arrangements (for publication) Recruitment arrangements 2
Recruitment arrangements (for publication) Recruitment material document 1.2
Recruitment arrangements (for publication) Recruitment material powerpoint 1.1
Subject information and informed consent form (for publication) Appendiks ICF Bone marrow aspirate and biopsy 1
Subject information and informed consent form (for publication) Bilag 1 Tidsplan SOBER II 1
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) Directions for use semaglutide 1
Subject information and informed consent form (for publication) ICF adults 2.2
Subject information and informed consent form (for publication) ICF adults bone marrow aspirate and biopsy 1.1
Subject information and informed consent form (for publication) ICF extra visit 52 weeks after last visit 1
Subject information and informed consent form (for publication) ICF future biobank 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
Subject information and informed consent form (for publication) SIS 2.4
Subject information and informed consent form (for publication) SIS bone marrow aspirations and biopsies 1.3
Subject information and informed consent form (for publication) SIS bone marrow aspirations and biopsies clean 1.1
Subject information and informed consent form (for publication) SIS clean 2.1
Subject information and informed consent form (for publication) SIS extra visit 52 weeks after last visit 1
Summary of Product Characteristics (SmPC) (for publication) SmPC Rybelsus 1
Synopsis of the protocol (for publication) Protocol synopsis_ENG 2023-505959-45-00 1.3

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-06-16 Denmark Acceptable
2023-08-24
 2023-09-07
2 SUBSTANTIAL MODIFICATION SM-1 2024-04-12 Denmark Acceptable
2024-05-14
 2024-05-23
3 SUBSTANTIAL MODIFICATION SM-4 2024-05-23 Denmark Acceptable
2024-05-28
 2024-05-28
4 NON SUBSTANTIAL MODIFICATION NSM-3 2024-06-21 Acceptable
2024-05-28
5 SUBSTANTIAL MODIFICATION SM-6 2025-01-12 Denmark Acceptable
2025-03-07
 2025-03-07
6 SUBSTANTIAL MODIFICATION SM-7 2025-10-23 Denmark Acceptable
2025-11-13
 2025-11-13

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