Treatment of adynamic bone disorder with parathyroid hormone in patients with chronic kidney disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Herlev Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

20 May 2021 → ongoing

Decision date (initial)

2023-07-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-506853-39-00

EudraCT number

2018-003888-56

ClinicalTrials.gov

NCT04522622

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of this trial is to evaluate whether 18 months of treatment with teriparatide is more efficient than no treatment on improvement of bone metabolism in patients with chronic kidney disease and adynamic bone disorder.

Conditions and MedDRA coding

Adynamic bone disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥18 years
2. CKD stage 4-5D (eGFR ≤29 ml/min) according to KDIGO (Kidney Disease Improving Global Outcome) definition
3. DEXA scan with a T-score at the total hip, femoral neck or lumbar spine (L1-4) ≤-2 (or Z-score ≤-2) in a minimum of 2 vertebrae (for patients with active oral prednisolone treatment ≥ 5 mg/day for minimum 3 months the T-score or Z-score limit is <-1) and/or former fragility fracture (vertebral, hip, for- or upper arm, ankle) assessed with VFA or x-ray of the columna
4. Patients with expected adynamic bone disorder, based on BSAP≤21 µg/l (11) or biopsy-verified low bone turnover

Exclusion criteria 21

1. Hypercalcemia defined as sustained ionized calcium >1.35 mmol/l
2. Patients who have undergone a kidney transplantation within the last 12 months
3. 25 hydroxyvitamin D2 and D3 <50 nmol/l (Patients may be rescreened after correction)
4. Inability to administer teriparatide
5. Reduced liver function (ALAT >3x upper limit of normal or bilirubin > 2x upper limit of normal)
6. Pregnancy, lactation or fertile women (Post-menopausal females are not considered fertile) not using safe anticonception (the following contraceptive methods are considered appropriate: Intrauterine device (IUD) or hormonal anticontraceptive (oral contraceptives, implant, transdermal patches, vaginal ring or depot injection)).
7. Hypersensitivity to the active substance in teriparatide or to any of the excipients or content
8. Inability to provide informed consent
9. Medical conditions or treatments that may interfere with assessments of the outcomes of the trial
10. Drug or alcohol abuse
11. Previous fracture within the last 6 months (Patients may be rescreened after the 6 months)
12. Unable to participate in a clinical study based on the judgement by the local investigator
13. For those participating in the bone biopsy procedure: 1) Hypersensitivity to any of the tetracyclines or to any of the excipients or content, 2) Treatment with anticoagulants (vitamin K antagonists, NOAC, unfractionated or low-molecular heparin or antiplatelet agents that, due to clinical indication, can’t be paused 3) Disturbances in thrombosis and/or haemostasis
14. For those participating in pulse wave measurements: 1) Atrial fibrillation, 2) Aorta stenosis
15. Previous calciphylaxis
16. Thyroid disturbances not adequately treated based on the opinion by the clinician (Patients may be rescreened after treatment optimization)
17. Treatment with digoxin
18. Paget’s disease or other metabolic bone disorders
19. Antiresorptive or bone anabolic medication during the last 24 months (for bisphosphonates it is only during the last 12 months)
20. Former or present malignant disease (except skin basal or planocellular carcinoma)
21. Previous external beam or implant radiation therapy to the skeleton

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The difference between the two groups (treated versus controls) in changes in BSAP after 18 months

Secondary endpoints 13

1. Changes between baseline and 18 months as well as differences between treated and untreated in: Number of patients who no longer have adynamic bone disorder based on a BSAP >21 µg/l
2. Changes between baseline and 18 months as well as differences between treated and untreated in: BMD at the lumbar spine, antebrachium, femoral neck and total hip
3. Changes between baseline and 18 months as well as differences between treated and untreated in: Incidence of fragility fractures and vertebral fractures assessed using vertebral fracture assessment (VFA) or x-ray of columna
4. Changes between baseline and 12 months as well as differences between treated and untreated in: Bone microarchitecture, volumetric BMD, bone geometry and bone strength assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)
5. Changes between baseline and 12 months as well as differences between treated and untreated in: Regional bone formation using 18F-NAF PET/CT
6. Changes between baseline and 18 months as well as differences between treated and untreated in: P-parathyroid hormone (intact, whole and nonoxidated-PTH), p-ionised calcium, p-phosphate, p-magnesium, p-FGF-23 and p-sclerostin
7. Changes between baseline and 18 months as well as differences between treated and untreated in: Bone microstructure by micro-computer tomography (µCT) of the bone biopsy
8. Changes between baseline and 12 months as well as differences between treated and untreated in: Static and dynamic bone histomorphometry classified by the TMV classification assessed by bone biopsy
9. Changes between baseline and 18 months as well as differences between treated and untreated in: Detailed histology of underlying cellular mechanisms using a combination of immunostainings and advanced in situ hybridizations on the bone biopsy
10. Changes between baseline and 18 months as well as differences between treated and untreated in: Bone turnover markers i.e. intact PINP, TRAP5b, osteocalcin, RANKL and OPG
11. Changes between baseline and 18 months as well as differences between treated and untreated in: 24-hour blood pressure and pulse wave measurements including velocity
12. Changes between baseline and 18 months as well as differences between treated and untreated in: T50, NT-proBNP as well as other cardiovascular biomarkers
13. Changes between baseline and 18 months as well as differences between treated and untreated in: The incidence of adverse reactions

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Herlev Hospital

Sponsor organisation

Herlev Hospital

Address

Herlev Ringvej 75

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Herlev Hospital

Contact name

Ditte Hansen

Public contact point

Organisation

Herlev Hospital

Contact name

Ditte Hansen

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 3 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