Longjohn Amgen Study - Effect of Denosumab...

NCT02444585 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: HS-14-00135
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of the proposed study is to quantify bone loss around non-cemented total hip replacement femoral and acetabular components using DEXA analysis in patients receiving Prolia (denosumab) in the first year of follow up after total hip joint replacement surgery, and to compare this to bone loss in control hip replacement patients receiving a placebo. The primary outcome variable will be the difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group, calculated as a percentage, in Gruen Zone 7, the proximal medial calcar region of the femur, over a follow-up period of 12 post-operative months. The secondary objectives will be to assess the following variables:

• Bone turnover differences between the experimental group taking denosumab and the placebo control group, utilizing serum C-terminal cross-linking telopeptides of type I collagen (CTX-I) (bone resorption) and N-terminal propeptides of type I procollagen (P1NP) (bone formation).
• Difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group, calculated as a percentage, in each of Gruen Zones 1 through 6, periprosthetic femur.
• Difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group, calculated as a percentage, in each of DeLee and Charnley's Zones 1 through 3, periprosthetic acetabulum. Exploratory objectives will be to assess difference in loss of bone mineral density in the contralateral, or non-operated femur for both experimental and control groups, and to determine the role that covariates such as weight, gender, age, baseline BMD, and implant type have on percent change in BMD at 12 months.

Conditions

Arthroplasty, Replacement, Hip

Outcome Measures

Primary Outcomes (1)

• Change in Bone Mineral Density

  The primary outcome variable will be the difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group.

  One Year

Secondary Outcomes (1)

• Bone Turnover Markers

  One Year

Study Arms (2)

Denosumab

EXPERIMENTAL

Drug for prevention of bone loss

Drug: Denosumab

Control

PLACEBO COMPARATOR

Hip Replacement Patient without Drug

Drug: Denosumab

Interventions

Denosumab DRUG

Intended to prevent periprosthetic loss of bone mineral density

Also known as: Prolia

Control; Denosumab

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Current use of medications that may affect bone and mineral metabolism (e.g., glucocorticoids, diuretics, estrogen, oral contraceptives, tamoxifen, bisphosphonates, raloxifene, calcitonin, PTH, anticonvulsants, immunosuppressants), and subjects with a history of any disease that affects bone and mineral metabolism (e.g., thyrotoxicosis, hyperparathyroidism, hypocalcemia hypoparathyroidism, chronic renal failure, Cushing's disease, rheumatoid arthritis, hematological disease, alcohol abuse \> 3 drinks a day), cancer. Additionally, patients who are taking immunosuppressants will be excluded. Patients who have been treated with anti-TNF in the past 3 months will be excluded. Patients with hypocalcemia or patients who have used bisphosphonates in the 2-3 years prior to the surgery will be excluded. Additionally, patients with creatinine clearance rates below 30 ml/minwill be excluded, as will patients with severe vitamin D deficiencies (\<12 ng/ml). Patients with decreased hepatic function as measured by AST, ALT, Alkaline Phosphatase or Total Bilirubin will be excluded from the study. Patients who have had any solid organ or bone marrow transplants will be excluded. Patients who have a history of malignancy within the past 5 years, with the exception of basal cell carcinoma or cervical carcinoma in situ, will be excluded. Additionally, as the incidence of serious infections may be higher in patients treated with denosumab, patients with poorly controlled diabetes/HbA1C will be excluded.

Sponsors & Collaborators

• University of Southern California: lead
• Orthopaedic Institute for Children: collaborator

Study Sites (1)

Keck Medicine of USC

Los Angeles, California, 90033, United States

Location

MeSH Terms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Donald Longjohn, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

• Edward Ebramzadeh, PhD

  Orthopaedic Institute for Children (Orthopaedic Hospital)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Orthopaedics

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 14, 2015
• Study Start: February 28, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: November 10, 2020

Record last verified: 2020-11

Locations

US (1)