The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients

NCT03960554 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAS3103
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 2 Multi-Center Clinical Trial (safety and effectiveness trial) in 60 patients (40 denosumab; 20 placebo) who have had a kidney transplant for 12-months or longer with more than 30% of kidney function. The investigators will test whether denosumab safely improves bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and improves bone strength by high resolution peripheral quantitative computed tomography (HR-pQCT) in the subset of patients recruited at Columbia University Irving Medical Center. These data will inform the development and execution of a larger trial to test if denosumab prevents fractures in kidney transplant recipients.

Conditions

Osteoporosis; Renal Osteodystrophy; Kidney Transplant; Complications

Keywords

Denosumab; Bone density; Kidney transplant; Prolia

Outcome Measures

Primary Outcomes (2)

• Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA)

  BMD will be measured to determine if 1-year of treatment with denosumab changes BMD as measured by DXA.

  12 months

• Estimated Bone Strength Measured by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging

  Estimated bone mechanical competence will be measured by HR-pQCT.

  12 months

Study Arms (2)

Active drug

ACTIVE COMPARATOR

Denosumab 60 mg subcutaneous injection every 6 months for 12 months (i.e., 2 injections)

Drug: Denosumab Inj 60 mg/ml

Placebo

PLACEBO COMPARATOR

Placebo subcutaneous injection every 6 months for 12 months (i.e., 2 injections)

Other: Placebo

Interventions

Denosumab Inj 60 mg/ml DRUG

Treatment will be administered by study personnel as a subcutaneous injection every 6-months for one year.

Also known as: Prolia

Active drug

Placebo OTHER

Placebo will be administered by study personnel as a subcutaneous injection every 6-months for one year.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women
• All race-ethnicities
• Age ≥ 18 years
• ≥ 12-months after kidney transplantation (living or deceased donor recipient)
• Stable allograft function over the previous year defined as:
• No rejections
• No more than a 15% decline in Glomerular filtration rate (GFR) over the prior year
• Allograft GFR ≥ 30 mL/minute/1.73 m2 (MDRD or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) per local lab reporting)
• OHD ≥ 30 ng/mL (determined at screening visit)
• Serum calcium ≥ 9.0 mg/dL (determined at screening visit)
• T-Score at the spine including and between -1.0 and -3.5 (determined at screening visit)
• Must have had a routine dental exam within 6-months of study recruitment
• Must agree to continue with routine dental exams over the course of the study
• Has not undergone an invasive dental procedure (i.e., tooth extraction, dental implants, oral surgery) within ≤ 3-months of recruitment
• Must agree to referral to metabolic bone disease specialist at the end of the study

You may not qualify if:

• Allograft GFR \< 30 mL/minute/1.73 m2 (MDRD or CKD-EPI per local lab reporting)
• Within 24-months of starting renal replacement therapy
• Prevalent or occult vertebral fractures
• History of post-transplantation non-basal cell carcinoma cancers
• Non-ambulatory
• Malignancy requiring chemotherapy or metastatic to bone
• Non-transplant related metabolic bone diseases that alter bone mineral density, including but not limited to Primary hyperparathyroidism, Paget's, Osteogenesis Imperfecta
• Within one-year of parathyroidectomy
• Untreated hyperthyroidism for 6-months or longer
• Untreated hypothyroidism for 6-months of longer
• Medical diseases (end stage liver, lung or heart, intestinal malabsorption)
• Use within the prior year of bisphosphonates, teriparatide, selective estrogen receptor modulators, testosterone, estrogen, denosumab, abaloparatide, calcitonin, and romosozumab
• Allergy to components within the denosumab preparation or to denosumab
• Weight \> 300 pounds
• Parathyroid hormone (PTH) \> 450 pg /mL

Sponsors & Collaborators

• Thomas Nickolas, MD MS: lead

Study Sites (3)

Northwestern University, Feinburg School of Medicine

Chicago, Illinois, 60611, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Osteoporosis; Chronic Kidney Disease-Mineral and Bone Disorder

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Rickets; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hyperparathyroidism, Secondary; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Due to the COVID-19 pandemic, this study was terminated early and no Outcome Measure data was collected from participants.

Results Point of Contact

• Title: Thomas L. Nickolas MD
• Organization: Columbia University Irving Medical Center

tln2001@cumc.columbia.edu

212-305-5020

Study Officials

• Thomas Nickolas, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The investigators and clinical research coordinators will be blinded to treatment assignment for the duration of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 23, 2019
• Study Start: January 16, 2020
• Primary Completion: December 2, 2021
• Study Completion: December 2, 2021
• Last Updated: July 25, 2024
• Results First Posted: July 25, 2024

Record last verified: 2024-07

Locations

US (3)