Early Effects of Abaloparatide on Tissue-Based Indices of Bone Formation and Resorption

NCT03710889 | Completed Phase 3 Results FDA Drug

• 1 other identifier: BA058-05-020
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

The objective of this study is to measure the early effects of abaloparatide on tissue-based bone formation using samples obtained by transiliac crest bone biopsy after quadruple fluorochrome labeling.

Conditions

Osteoporosis, Postmenopausal; Osteoporosis; Osteoporosis Vertebral; Osteoporosis Risk; Osteoporosis Fracture; Osteoporosis Localized to Spine; Osteoporosis, Age-Related; Osteoporosis Senile; Osteoporosis of Vertebrae

Keywords

BA058; abaloparatide; TYMLOS®; Bone metabolism; Osteoporosis; Fracture; Bone loss

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Envelope at Month 3

  Change in dynamic histomorphometry indices was assessed in the cancellous envelope.

  Baseline (Day 1), Month 3

Secondary Outcomes (3)

• Change From Baseline in Bone Formation Rate/Bone Surface (BFR/BS) in the Cancellous Envelope at Month 3

  Baseline (Day 1), Month 3

• Change in Serum Procollagen Type I N-terminal Propeptide (s-P1NP) From Baseline at Month 1 and Month 3

  Baseline (Day 1), Months 1 and 3

• Change in Serum Carboxy-Terminal Cross-Linking Telopeptide of Type I Collagen (s-CTX) From Baseline at Month 1 and Month 3

  Baseline (Day 1), Months 1 and 3

Study Arms (1)

Abaloparatide

EXPERIMENTAL

Participants self-administered a single daily dose of 80 micrograms (µg) of abaloparatide subcutaneously (SC) during the treatment period. Participants were instructed to use a new injection pen after each 30-day period.

Drug: Abaloparatide

Interventions

Abaloparatide DRUG

Abaloparatide is a novel, synthetic, 34 amino acid peptide designed to be a potent and selective activator of the PTH/PTH-related protein (PTHrP) type 1 receptor (PTHR1) signaling pathway with 41% homology to PTH\[1-34\] and 76% homology to human PTHrP\[1-34\].

Also known as: TYMLOS®, BA058

Abaloparatide

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible to participate in this study:
• The participant is a healthy ambulatory postmenopausal female from 50 to 85 years of age (inclusive) with osteoporosis.
• The participant has been postmenopausal for at least 5 years. Postmenopausal status will be established by a history of amenorrhea for at least 5 years and by an elevated follicle stimulating hormone (FSH) value of ≥30 international units(IU)/liter (L).
• The participant has a BMD T-score ≤-2.5 at the lumbar spine (L1-L4) or hip (femoral neck or total hip) by dual-energy x-ray absorptiometry (DXA) or lumbar spine or hip BMD T-score ≤-2.0 with a history of low trauma vertebral, forearm, humerus, sacral, pelvic, hip, femoral, or tibial fracture sustained within 5 years prior to enrollment. These fractures must be documented by radiograph or hospital report.
• The participant is in good general health as determined by medical history and physical examination (including vital signs), has a body mass index (BMI) of 18.5 to 33, inclusive, and is without evidence of clinically significant abnormality in the opinion of the Investigator.
• The participant has serum calcium (albumin-corrected), parathyroid hormone (PTH) (1-84), phosphorus, and alkaline phosphatase levels all within the normal range during the Screening Period. Any participant with an elevated alkaline phosphatase value, and who meets all other entry criteria, is required to have a normal bone-specific alkaline phosphatase result to be enrolled.
• The participant has serum 25-hydroxyvitamin D values ≥ 20 nanograms (ng)/milliliter (mL) and within the normal range. Participants with serum 25-hydroxyvitamin D levels \< 20 ng/ml may be treated with vitamin D3 and re-tested once.
• The participant's resting 12-lead electrocardiogram (ECG) obtained during screening shows no clinically significant abnormality.
• The participant has read, understood, and signed the written informed consent form.

You may not qualify if:

• Participants with any of the following characteristics are not eligible to participate in the study:
• Presence of abnormalities of the lumbar spine that would prohibit assessment of lumbar spine BMD, defined as having at least 2 radiologically evaluable vertebrae within L1-L4.
• Unevaluable hip BMD or participants who have undergone bilateral hip replacement (unilateral hip replacement is acceptable).
• History of bone disorders (for example, Paget's disease) other than postmenopausal osteoporosis.
• Clinically significant abnormality of serum hemoglobin, hematocrit, white blood cells (WBC) and platelets, coagulation, or usual serum chemistry: electrolytes, renal function, liver function and serum proteins.
• Unexplained elevation of serum alkaline phosphatase.
• History of radiotherapy (radiation therapy), other than radioiodine.
• History of bleeding disorder that would preclude a bone biopsy, in the opinion of the Investigator.
• History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular, gastrointestinal, endocrine, central nervous system, hematologic or metabolic diseases, or immunologic, emotional and/or psychiatric disturbances to a degree that would interfere with the interpretation of study data or compromise the safety of the participant.
• History of Cushing's disease, hyperthyroidism, hypo- or hyperparathyroidism, or malabsorptive syndromes within the past year.
• History of significantly impaired renal function (serum creatinine \> 177 micromoles \[µmol\]/L or \>2.0 milligrams \[mg\]/deciliter \[dL\]). If the serum creatinine is \>1.5 and ≤ 2.0 mg/dL, the calculated creatinine clearance (Cockcroft-Gault) must be ≥ 30 mL/minute (min).
• History of any cancer within the past 5 years (other than basal cell or squamous cell cancer of the skin).
• History of osteosarcoma at any time or a history of hereditary disorders which could predispose the participant to osteosarcoma.
• History of nephrolithiasis or urolithiasis within the past 5 years.
• Participant known to be positive for hepatitis B, hepatitis C, or human immunodeficiency virus infection (HIV-1 or HIV-2). Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection or acute or chronic hepatitis.

Sponsors & Collaborators

• Radius Health, Inc.: lead

Study Sites (4)

Panorama Orthopedics & Spine Center

Golden, Colorado, 80401, United States

Location

Center for Advanced Research & Education

Gainesville, Georgia, 30501, United States

Location

Harvard Medical School

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Detroit, Michigan, 48230, United States

Location

Related Publications (3)

• Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ. Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology. 2016 Jan;157(1):141-9. doi: 10.1210/en.2015-1726. Epub 2015 Nov 12.

  PMID: 26562265 BACKGROUND

• Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Valter I, Fitzpatrick LA, Riis BJ, Christiansen C, Bilezikian JP, Black D. Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial. Mayo Clin Proc. 2017 Feb;92(2):200-210. doi: 10.1016/j.mayocp.2016.10.009.

  PMID: 28160873 BACKGROUND

• Dempster DW, Zhou H, Rao SD, Recknor C, Miller PD, Leder BZ, Annett M, Ominsky MS, Mitlak BH. Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With Osteoporosis. J Bone Miner Res. 2021 Apr;36(4):644-653. doi: 10.1002/jbmr.4243. Epub 2021 Jan 28.

  PMID: 33434314 DERIVED

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Osteoporosis; Osteoporotic Fractures; Fractures, Bone; Bone Diseases, Metabolic

Interventions

abaloparatide

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Wounds and Injuries

Results Point of Contact

• Title: Associate Director, Clinical Operations
• Organization: Radius Health, Inc.

info@radiuspharm.com

(617) 551-4000

Study Officials

• Medical Director

  Radius Health, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 18, 2018
• Study Start: September 20, 2018
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: October 15, 2021
• Results First Posted: October 15, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)