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A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases.
Cancer. 2003 Feb 01; 97(3 Suppl):887-92.C

Abstract

BACKGROUND

Osteoprotegerin (OPG) is a decoy receptor for OPG ligand (OPGL), or receptor activator of NF-kappaB ligand (RANKL). RANKL/RANK interaction is important in terminal differentiation and activation of osteoclasts. In binding to RANKL, OPG blocks differentiation and activation of osteoclasts. AMGN-0007 is a recombinant OPG construct developed as a potential therapeutic agent in the treatment of bone disease.

METHODS

A randomized, double-blind, double-dummy, active-controlled, single-dose, dose escalation study was conducted to determine the safety and effect on bone resorption of AMGN-0007 in patients with multiple myeloma (n = 28) or breast carcinoma (n = 26) with radiologically confirmed lytic bone lesions. Patients were randomized (3:1 ratio) to receive a single dose of either AMGN-0007 (subcutaneously [SC]) or pamidronate (90 mg intravenously) and were followed for 56 days. Medications or other diseases affecting bone metabolism and chemotherapy within 28 days of dosing were exclusion criteria. Biologic activity of AMGN-0007 was assessed by measurement of the surrogate marker of bone resorption, urinary N-telopeptide of collagen (NTX).

RESULTS

AMGN-0007 caused a rapid, sustained, dose-dependent decrease in NTX/creatinine levels, which was at least comparable to the profile observed with pamidronate. Four serious adverse events were reported, three in breast carcinoma patients: a fracture in the left femur (pamidronate, considered unrelated), extreme fatigue (0.3 mg/kg AMGN-0007, considered unrelated), and congestive heart failure (1.0 mg/kg AMGN-0007, considered by the investigator to be probably related to doxorubicin and radiation therapy); one event occurred in a multiple myeloma patient: Herpes zoster (pamidronate, considered unrelated). Two multiple myeloma patients (1.0 mg/kg AMGN-0007) had albumin-adjusted serum calcium levels of 1.9 mmol/L on Day 8 but without clinical symptoms.

CONCLUSIONS

A single SC dose of AMGN-0007 suppressed bone resorption as indicated by a rapid, sustained, and profound decrease of urinary NTX/creatinine in multiple myeloma and breast carcinoma patients. Changes were comparable to those with pamidronate. AMGN-0007 was well tolerated.

Authors+Show Affiliations

Unit of Endocrinology, Institut Jules Bordet, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12548591

Citation

Body, Jean-Jacques, et al. "A Phase I Study of AMGN-0007, a Recombinant Osteoprotegerin Construct, in Patients With Multiple Myeloma or Breast Carcinoma Related Bone Metastases." Cancer, vol. 97, no. 3 Suppl, 2003, pp. 887-92.
Body JJ, Greipp P, Coleman RE, et al. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer. 2003;97(3 Suppl):887-92.
Body, J. J., Greipp, P., Coleman, R. E., Facon, T., Geurs, F., Fermand, J. P., Harousseau, J. L., Lipton, A., Mariette, X., Williams, C. D., Nakanishi, A., Holloway, D., Martin, S. W., Dunstan, C. R., & Bekker, P. J. (2003). A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer, 97(3 Suppl), 887-92.
Body JJ, et al. A Phase I Study of AMGN-0007, a Recombinant Osteoprotegerin Construct, in Patients With Multiple Myeloma or Breast Carcinoma Related Bone Metastases. Cancer. 2003 Feb 1;97(3 Suppl):887-92. PubMed PMID: 12548591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. AU - Body,Jean-Jacques, AU - Greipp,Philip, AU - Coleman,Robert E, AU - Facon,Thierry, AU - Geurs,Filip, AU - Fermand,Jean-Paul, AU - Harousseau,Jean-Luc, AU - Lipton,Allan, AU - Mariette,Xavier, AU - Williams,Catherine D, AU - Nakanishi,Arline, AU - Holloway,Donna, AU - Martin,Steven W, AU - Dunstan,Colin R, AU - Bekker,Pirow J, PY - 2003/1/28/pubmed PY - 2003/4/15/medline PY - 2003/1/28/entrez SP - 887 EP - 92 JF - Cancer JO - Cancer VL - 97 IS - 3 Suppl N2 - BACKGROUND: Osteoprotegerin (OPG) is a decoy receptor for OPG ligand (OPGL), or receptor activator of NF-kappaB ligand (RANKL). RANKL/RANK interaction is important in terminal differentiation and activation of osteoclasts. In binding to RANKL, OPG blocks differentiation and activation of osteoclasts. AMGN-0007 is a recombinant OPG construct developed as a potential therapeutic agent in the treatment of bone disease. METHODS: A randomized, double-blind, double-dummy, active-controlled, single-dose, dose escalation study was conducted to determine the safety and effect on bone resorption of AMGN-0007 in patients with multiple myeloma (n = 28) or breast carcinoma (n = 26) with radiologically confirmed lytic bone lesions. Patients were randomized (3:1 ratio) to receive a single dose of either AMGN-0007 (subcutaneously [SC]) or pamidronate (90 mg intravenously) and were followed for 56 days. Medications or other diseases affecting bone metabolism and chemotherapy within 28 days of dosing were exclusion criteria. Biologic activity of AMGN-0007 was assessed by measurement of the surrogate marker of bone resorption, urinary N-telopeptide of collagen (NTX). RESULTS: AMGN-0007 caused a rapid, sustained, dose-dependent decrease in NTX/creatinine levels, which was at least comparable to the profile observed with pamidronate. Four serious adverse events were reported, three in breast carcinoma patients: a fracture in the left femur (pamidronate, considered unrelated), extreme fatigue (0.3 mg/kg AMGN-0007, considered unrelated), and congestive heart failure (1.0 mg/kg AMGN-0007, considered by the investigator to be probably related to doxorubicin and radiation therapy); one event occurred in a multiple myeloma patient: Herpes zoster (pamidronate, considered unrelated). Two multiple myeloma patients (1.0 mg/kg AMGN-0007) had albumin-adjusted serum calcium levels of 1.9 mmol/L on Day 8 but without clinical symptoms. CONCLUSIONS: A single SC dose of AMGN-0007 suppressed bone resorption as indicated by a rapid, sustained, and profound decrease of urinary NTX/creatinine in multiple myeloma and breast carcinoma patients. Changes were comparable to those with pamidronate. AMGN-0007 was well tolerated. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/12548591/A_phase_I_study_of_AMGN_0007_a_recombinant_osteoprotegerin_construct_in_patients_with_multiple_myeloma_or_breast_carcinoma_related_bone_metastases_ DB - PRIME DP - Unbound Medicine ER -