A Safety, Tolerability and Efficacy Study of ACE-011 in Patients With Osteolytic Lesions of Multiple Myeloma

A Phase 2a, Multi-Center, Randomized, Multiple-Dose Study to Evaluate the Safety, Tolerability and Efficacy of ACE-011 (hActRIIA-IgG1) in Patients With Osteolytic Lesions of Multiple Myeloma

Multi-center, randomized, multiple-dose study to evaluate the safety, tolerability and efficacy of ACE-011 in patients with osteolytic lesions of multiple myeloma.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: Placebo; Biological: ACE-011

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Investigative Site
  • Saint-Petersburg, Russian Federation
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Patient at least 18 years of age with stage II or III multiple myeloma
• One or more lytic bone lesions
• If currently receiving bisphosphonate therapy, have been on a stable dose for ≥ 2 months before dosing day 1 or must not have received bisphosphonates within 2 months of dosing day 1
• If patient has undergone previous autologous or allogenic hematopoietic stem cell transplantation (HSCT), they must be stable (in the opinion of the investigator) and be a minimum of 6 months since HSCT
• Has planned HSCT for the duration of the study
• Has moles or lesions that are currently undiagnosed, but are suspect for malignancy
• Has an underlying condition that may result in abnormal bone metabolism other than cancer related bone lesions, such as a history of hyperparathyroidism, hypoparathyroidism, hypocalcemia, rheumatoid arthritis, myeloproliferative disorder, gout, Paget's disease of the bone, or osteomalacia; patients with a diagnosis of osteoporosis prior to multiple myeloma diagnosis are eligible to participate.

Key Exclusion Criteria:

• Known underlying condition that may result in abnormal bone metabolism other than cancer related bone lesions
• History of polyneuropathy ≥ grade 3
• Patients with plasma cell leukemia
• Planned stem cell transplant (HSCT) or radiation for the duration of the study
• Skeletal related event within 2 weeks of study enrollment
• Has received erythropoiesis-stimulating agents (ESAs) within the last 21 days or is planned to receive ESAs during the course of the study
• Has received anti-myeloma therapy within the last 21 days
• Is scheduled to receive local radiation to bone during the course of the study
• Has taken estrogen, androgen, anabolic steroids, calcitonin or other bone-active drugs within 4 months of study enrollment
• Woman of childbearing potential (not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subcutaneous injection on days 1, 29, 57 and 85.	Biological: Placebo; Placebo given by the subcutaneous route of administration monthly for 4 doses.
Experimental: ACE-011 0.1 mg/kg; Subcutaneous injection of ACE-011 0.1 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).	Biological: ACE-011; ACE-011 given by the subcutaneous route of administration monthly for 4 doses.; Other Names: hActRIIA-IgG1
Experimental: ACE-011 0.3 mg/kg; Subcutaneous injection of ACE-011 0.3 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).	Biological: ACE-011; ACE-011 given by the subcutaneous route of administration monthly for 4 doses.; Other Names: hActRIIA-IgG1
Experimental: ACE-011 0.5 mg/kg; Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).	Biological: ACE-011; ACE-011 given by the subcutaneous route of administration monthly for 4 doses.; Other Names: hActRIIA-IgG1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with Treatment-emergent Adverse Experiences		Up to Day 169
Change from baseline at end of treatment in Bone Specific Alkaline Phosphatase (BSAP)	BSAP is a biomarker of bone formation.	Up to Day 169
Change from baseline at end of treatment in Serum intact procollagen type I N terminal propeptide (PINP)	PINP is a biomarker of bone formation.	Up to Day 169
Change from Baseline at End of Treatment in Serum C-terminal type I collagen telopeptide (CTX)	CTX is a bone resorption biomarker.	Up to Day 169
Change from Baseline at End of Treatment in Serum tartrate-resistant acid phosphatase isoform-5b (Tracp-5b)	Tracp-5b is a bone resorption biomarker.	Up to Day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline at End of Treatment in Hip Bone Mineral Density		Up to Day 169
Change from Baseline at End of Treatment in Lumbar Spine Bone Mineral Density		Up to Day 169
Summary of Investigator's Bone Lesion Assessment Based on Skeletal X-rays During Follow-up		Up to Day 169
Change from Baseline to End of Treatment in Participant-reported Bone Pain Assessment Using a Visual Analog Scale (VAS) Score		Up to Day 169
Participants with Skeletal-related Adverse Events		Up to Day 169
Pharmacokinetics - AUC	Area under the plasma concentration-time curve	Up to Day 169
Pharmacokinetics - Cmax	Maximum observed concentration	Up to 169 days
Pharmacokinetics - Tmax	Time to maximum observed concentration	Up to 169 days
Pharmacokinetics - t½	Elimination half-life	Up to 169 days
Pharmacokinetics - λz	Elimination rate constant	Up to 169 days
Pharmacokinetics - Vz/F	Volume of distribution	Up to 169 days
Pharmacokinetics - CL/F	Total clearance	Up to 169 days
Pharmacokinetics - Ka	Absorption rate constant	Up to 169 days

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Abderrahmane Laadem, MD, Celgene Corporation

Publications and helpful links

General Publications

• Abdulkadyrov KM, Salogub GN, Khuazheva NK, Sherman ML, Laadem A, Barger R, Knight R, Srinivasan S, Terpos E. Sotatercept in patients with osteolytic lesions of multiple myeloma. Br J Haematol. 2014 Jun;165(6):814-23. doi: 10.1111/bjh.12835. Epub 2014 Mar 21.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: September 3, 2008
• First Submitted That Met QC Criteria: September 3, 2008
• First Posted (Estimate): September 4, 2008

Study Record Updates

• Last Update Posted (Actual): October 24, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: A011-04