Safety and efficacy of oral semaglutide in hyperglycaemic patients after renal transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

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

3 Sep 2024 → ongoing

Decision date (initial)

2023-08-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Augustinus Foundation · Region Hovedstadens forskningsfond

External identifiers

EU CT number

2023-504159-29-01

WHO UTN

U1111-1277-9936

ClinicalTrials.gov

NCT05702931

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to establish whether oral semaglutide (Rybelsus) compared with placebo, both as add-on to standard-of-care, is non-inferior in regulating plasma glucose in patients with hyperglycaemia after renal transplantation.

Secondary objectives 1

1. Secondary objectives aim to evaluate the effect of oral semaglutide on renal graft function, weight, use of insulin, cardiovascular parameters and safety parameters (plasma semaglutide concentration, gastrointestinal side effects, dose of immunosuppressants).

Conditions and MedDRA coding

Hyperglycaemia after renal transplantation

Regulatory references

Plan to share IPD

No

IPD plan description

.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Written informed consent obtained before any trial-related procedures are performed
2. Male or female; age: 18–80 years
3. Diagnosis of post-transplant hyperglycaemia 10 to 40 days after transplantation: Fasting plasma glucose ≥ 7.0 mmol/L or an oral glucose tolerance test with at plasma glucose ≥ 11.1 mmol/L, or Pre-transplant type 2 diabetes: Receiving glucose-lowering treatment prior to kidney transplantation.
4. An eGFR > 15 ml/min/1.73 m2 10 to 40 days after renal transplantation
5. Subject must be willing and able to comply with trial protocol

Exclusion criteria 16

1. Type 1 diabetes
2. Inflammatory bowel disease
3. Previous bowel resection
4. Cardiac disease defined as decompensated heart failure (New York Heart Association class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last six months
5. Any acute condition or exacerbation of chronic condition that would in the investigator’s opinion interfere with the initial trial visit schedule and procedures.
6. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant, or are not using adequate contraceptive methods
7. Malignancy (except basal cell carcinoma)
8. Impaired liver function (plasma ALAT > two times upper reference levels)
9. Elevated amylase (plasma amylase > two times upper reference levels)
10. Dialysis
11. High risk immunological transplantation (not including ABO-incompatible or re-transplantation)
12. Early graft rejection (all rejections verified by biopsy, except borderline rejections. Study initiations can begin 5 days after last dose of rejection treatment with methylprednisolone)
13. Chronic pancreatitis/previous acute pancreatitis
14. Known or suspected hypersensitivity to trial or related products
15. Use of DPP-4 inhibitors within five days prior to screening
16. Use of GLP-1RA within 10 days prior to screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean sensor glucose (mmol/L) evaluated by CGM

Secondary endpoints 35

1. Percentage time in target range (3.9–10.0 mmol/L) as evaluated by CGM
2. Percentage time in tight glycaemic range (3.9–7.8 mmol/L)
3. Percentage time in hyperglycaemia (level 1 (10.1–13.9 mmol/L) and level 2 (above 13.9 mmol/L) evaluated by CGM
4. Glucose variability (standard deviation [mmol/L] and coefficient of variation [%]) evaluated by CGM
5. Glucose management indicator (mmol/mol and %) evaluated by CGM
6. HbA1c (mmol/mol and %)
7. Body weight (kg)
8. Body mass index (BMI) expressed as kg/m2
9. Creatinine (µmol/L)
10. eGFR (ml/min/1.73m2)
11. Systolic blood pressure (mmHg)
12. Diastolic blood pressure (mmHg)
13. Pulse (beats-per-min)
14. Urinary albumin-to-creatinine ratio (mg/g)
15. Plasma concentrations of cholesterol, low-and high-density lipoproteins (LDL and HDL, respectively) and triglycerides
16. Daily insulin dose (IE per day)
17. Daily dose of immunosuppressant (prednisone, cyclosporine, tacrolimus, mycophenolate mofetile)
18. Plasma concentration of semaglutide (nmol/L)
19. Plasma insulin (pmol/L)
20. C-peptide (nmol/L)
21. Homeostatic model assessment (HOMA) for assessing beta-cell function and insulin resistance
22. Blood concentrations of cyclosporine (µg/L) and tacrolimus (µg/L)
23. Dose-corrected plasma semaglutide concentration (nmol/L)
24. Plasma alanine transaminase (ALAT) (U/L)
25. Plasma amylase (U/L)
26. Gastrointestinal side effects evaluated using the Gastrointestinal symptom rating scale (GSRS) (Consist of 15 gastrointestinal symptoms that are each rated on a 7-point scale with 1 being "no discomfort" and 7 being "very severe discomfort")
27. Incidence of adverse events
28. Incidence of serious adverse events
29. Incidence of self-reported hypoglycaemic episodes
30. Incidence of out-of-target measures of blood tacrolimus and blood ciclosporin
31. Incidence of 25% increase in creatinine from discharge after renal transplantation
32. Incidence of admissions
33. Incidence of admissions due to dehydration
34. Incidence of renal graft rejection
35. Incidence of renal graft failure (defined as return to dialysis)

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Mads Hornum

Public contact point

Organisation

Rigshospitalet

Contact name

Mads Hornum

Third parties 1

Locations

1 EU/EEA country · 3 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 4 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