Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients

Osteoporosis Clinical Trial

— POSTOP  

Official title:

A Phase 3, Investigator-initiated, Randomized, Open-label Single-center Study of the Effect of Denosumab on the Prevention of Bone Mineral Density Loss After Renal Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01377467
• Other study ID #: UZH-NEP 2.1
• Status: Active, not recruiting
• Phase: Phase 3
• First received: June 20, 2011
• Last updated: July 28, 2014
• Start date: June 2011
• Est. completion date: October 2015

Study information

• Verified date: July 2014
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to examine the effect of denosumab on lumbar spine bone mineral density (BMD) after one year of treatment in newly transplanted renal allograft recipients. Secondary endpoints include BMD changes at the total hip and the femoral neck, changes in body height, changes in bone mineral metabolism parameters, incidence of fractures, and allograft function at one year. Safety measurements include the occurrence of rejection episodes, infectious complications, graft loss and mortality.

• Trial with medicinal product

Description:

Renal allograft recipients are at high risk to suffer a substantial loss of bone mineral density (BMD) within the first year after kidney transplantation. This loss of BMD correlates with an increased risk for the development of osteoporosis or worsening of pre-existing osteopenia/osteoporosis, heightening the risk for the subsequent occurrence of fractures. Renal allograft recipients are often treated with calcium and vitamin D preparations to prevent BMD loss. The addition of bisphosphonates can further improve BMD. However, bisphosphonates are potentially nephrotoxic and promote adynamic bone disease, and are therefore not regularly prescribed.

Receptor Activator of Nuclear factor- Kappa-B Ligand (RANKL) is a key molecule mediating development, activity, and survival of osteoclasts. Osteoporosis results in part from increased osteoclastic bone resorption, and therefore the inhibition of RANKL activity has become an obvious therapeutic strategy to prevent bone mineral density (BMD) loss and the development of osteoporosis.

The novel anti-osteoporotic drug denosumab (trade name Prolia®) is a fully human monoclonal antibody against RANKL. By inhibiting the development and the activity as well as reducing the survival of osteoclasts it decreases bone resorption and increases bone density.

The hypothesis of the present study is that denosumab has a beneficial effect on the loss of BMD in the first year after renal transplantation. The preservation of BMD is a surrogate parameter, generally predicting subsequent improvements in the occurrence rate of fractures. The hypothesis will be tested by studying the effect of denosumab on BMD in newly transplanted renal allograft recipients.

The purpose of the present trial is to study the effect of denosumab on BMD in kidney allograft recipients. The study participants will be treated for 1 year, receiving a total of 2 injections of the standard 60 mg dose at baseline and at 6 months.

Ninety sequential renal allograft recipients will be randomized 1:1 to receive two subcutaneous 60 mg denosumab injections within 14 days and 6 months following renal transplantation, or no treatment. All patients will also receive oral standard treatment with 1000 mg calcium plus 800 IU vitamin D.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: October 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

The key inclusion criteria are:

1. Male or female adult de novo kidney, kidney-pancreas or kidney-islet, or kidney-liver transplant recipients

2. Functioning graft within 28 days after transplantation (creatinine having decreased to <200 micromol/l without the need for dialysis)

3. Being on standard triple immunosuppression including a calcineurin antagonist (cyclosporine or tacrolimus), mycophenolate (MMF or MPA) and steroids, with or without induction treatment with basiliximab or anti-thymocyte globulin

Key exclusion criteria are:

1. Age <18 years

2. Rising creatinine after initial drop <200 micromol/l or creatinine >200 micromol/l at baseline

3. Evidence of early acute rejection, either suspected clinically and/or proven by biopsy

4. Presence of severe osteoporosis as evidenced by a T score <-4 at the hip, femoral neck or any of the 4 vertebrae L1 to L4

5. Evidence of severe hyper- or hypoparathyroidism (iPTH >800 ng/l or <10 ng/l)

6. Hypocalcemia (total calcium <1.8 mmol/l) or hypercalcemia (total calcium >2.7 mmol/l)

7. Steroid-free de novo immunosuppression scheme

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Osteoporosis
• Renal Insufficiency, Chronic

Intervention

Drug:
• Denosumab (Prolia)
60 mg s.c. injection at baseline and after 6 months

Locations

Country	Name	City	State
Switzerland	Division of Nephrology, University Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Rudolf Wuethrich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lumbar spine bone mineral density (BMD) after one year of treatment		Bone mineral density at 12 months	No
Secondary	Occurrence of fractures	BMD changes at the total hip and the femoral neck, changes in body height, and changes in bone mineral metabolism parameters, incidence of fractures, allograft function at one year, occurrence of infections	1 year	Yes