Abaloparatide and Pelvic Fracture Healing

NCT04249232 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2019-1978
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

This is a prospective randomized, double-blinded, placebo-controlled, phase 2, three-month study of the efficacy of abaloparatide in postmenopausal women and men ≥ 50 years of age with acute fractures of the pelvis (n=78). The primary outcome is CT image based evidence of fracture healing. The secondary aims are pain and physical performance measures at 3 months. This study will be extended with 9 months of open label abaloparatide to determine if any potential differences between the placebo and abaloparatide groups during the 3 months of treatment are evident and persist over time, even in patients who use abaloparatide after the three-month placebo controlled intervention.

Conditions

Fracture of Pelvis (Disorder)

Keywords

abaloparatide

Outcome Measures

Primary Outcomes (1)

• Efficacy for fracture healing- Measured by participant cortical bridging scores

  Score for cortical bridging on a CT exam at 3 months in abaloparatide versus placebo groups.

  3 months

Secondary Outcomes (6)

• Efficacy measure of participant pain score as assessed by the Numeric Rating Scale

  8 weeks

• Efficacy measure of participant pain score as assessed by the Numeric Rating Scale

  12 months

• Participant lower extremity function based on a score from the Continuous Summary Physical Performance Score. The measure of lower extremity physical function is an efficacy variable.

  3 months

• Participant lower extremity function based on a score from the Continuous Summary Physical Performance Score. The measure of lower extremity physical function is an efficacy variable.

  12 months

• Participant (percent) reporting narcotic use for pain

  8 weeks

Study Arms (2)

abaloparatide prefilled syringe

ACTIVE COMPARATOR

Abaloparatide-SC is supplied as a liquid, 3120 micrograms per 1.56 milliliter (2000 mcg/mL) in a single patient multi-use prefilled pen. The prefilled pen delivers 30 doses of abaloparatide, each containing 80 mcg of abaloparatide in 40 microliters of a sterile, clear, colorless solution. To be administered subcutaneously daily.

Drug: Abaloparatide 80 micrograms per Pen dose

Placebo prefilled syringe

PLACEBO COMPARATOR

For the placebo-SC a prefilled multi-use pen injector cartridge is designed to deliver 30 doses of placebo each in 40 microliters of sterile, clear, colorless solution to be administered subcutaneously daily.

Drug: Placebo prefilled injector pen

Interventions

Abaloparatide 80 micrograms per Pen dose DRUG

prefilled injector pen to deliver 80 micrograms daily subcutaneously

Also known as: Tymlos

abaloparatide prefilled syringe

Placebo prefilled injector pen DRUG

prefilled injector pen to deliver inactive solution daily subcutaneously

Also known as: placebo

Placebo prefilled syringe

Eligibility Criteria

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

You may qualify if:

• Postmenopausal women and men \>50 years of age with acute pelvic fractures, occurring with minimal trauma, presenting to Mount Sinai, New York University, New York Presbyterian-Queens, Hospital for Special Surgery, or New York Hospital (Cornell Medical) within one month of the onset of symptoms.

You may not qualify if:

• Persons unable to complete the NRS and other surveys based on assessment by the study doctor.
• Previously (prior to fracture) non-ambulatory subjects
• Hypersensitivity to ABALOPARATIDE
• Patients with increased risk of osteosarcoma: Paget's disease, history of radiation treatment
• Patients with active hypercalcemia based on serum calcium above the upper limit of normal.
• Serum creatinine cannot be elevated more than 1.5 times above upper normal limit for age
• Current diagnosis of hyperparathyroidism and other metabolic bone disease including osteogenesis imperfecta
• Normal alkaline phosphatase levels will not be used as an entrance criterion because most fracture patients will have elevations due to the acute fracture. However, we will attempt to obtain lab tests from the period prior to fracture to determine if they were normal. If unexplained elevations in alkaline phosphatase (more than 1.5 times above the upper limit of normal) are found in labs prior to the fracture, we will exclude that subject.
• Diagnosis of metastatic cancer within the past 10 years; primary bone cancer or multiple myeloma at any time. For other primary active non-skin cancers (diagnosed within the last 5 years), the patient's oncologist should be consulted to determine participant eligibility.

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Weill Medical College of Cornell University: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• New York University: collaborator
• Westchester Medical Center: collaborator

Study Sites (3)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Related Publications (14)

• Prieto-Alhambra D, Aviles FF, Judge A, Van Staa T, Nogues X, Arden NK, Diez-Perez A, Cooper C, Javaid MK. Burden of pelvis fracture: a population-based study of incidence, hospitalisation and mortality. Osteoporos Int. 2012 Dec;23(12):2797-803. doi: 10.1007/s00198-012-1907-z. Epub 2012 Feb 4.

  PMID: 22310957 BACKGROUND

• Kannus P, Palvanen M, Niemi S, Parkkari J, Jarvinen M. Epidemiology of osteoporotic pelvic fractures in elderly people in Finland: sharp increase in 1970-1997 and alarming projections for the new millennium. Osteoporos Int. 2000;11(5):443-8. doi: 10.1007/s001980070112.

  PMID: 10912847 BACKGROUND

• Andrich S, Haastert B, Neuhaus E, Neidert K, Arend W, Ohmann C, Grebe J, Vogt A, Jungbluth P, Rosler G, Windolf J, Icks A. Epidemiology of Pelvic Fractures in Germany: Considerably High Incidence Rates among Older People. PLoS One. 2015 Sep 29;10(9):e0139078. doi: 10.1371/journal.pone.0139078. eCollection 2015.

  PMID: 26418971 BACKGROUND

• Benzinger P, Becker C, Kerse N, Bleibler F, Buchele G, Icks A, Rapp K. Pelvic fracture rates in community-living people with and without disability and in residents of nursing homes. J Am Med Dir Assoc. 2013 Sep;14(9):673-8. doi: 10.1016/j.jamda.2013.03.012. Epub 2013 May 13.

  PMID: 23680402 BACKGROUND

• Melton LJ 3rd, Sampson JM, Morrey BF, Ilstrup DM. Epidemiologic features of pelvic fractures. Clin Orthop Relat Res. 1981 Mar-Apr;(155):43-7.

  PMID: 7226629 BACKGROUND

• Alnaib M, Waters S, Shanshal Y, Caplan N, Jones S, St Clair Gibson A, Kader D. Combined pubic rami and sacral osteoporotic fractures: a prospective study. J Orthop Traumatol. 2012 Jun;13(2):97-103. doi: 10.1007/s10195-012-0182-2. Epub 2012 Mar 6.

  PMID: 22391943 BACKGROUND

• Krappinger D, Kammerlander C, Hak DJ, Blauth M. Low-energy osteoporotic pelvic fractures. Arch Orthop Trauma Surg. 2010 Sep;130(9):1167-75. doi: 10.1007/s00402-010-1108-1. Epub 2010 Jun 3.

  PMID: 20521061 BACKGROUND

• Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 2011 Sep 7;93(17):1583-7. doi: 10.2106/JBJS.J.01379.

  PMID: 21915572 BACKGROUND

• Ellegaard M, Jorgensen NR, Schwarz P. Parathyroid hormone and bone healing. Calcif Tissue Int. 2010 Jul;87(1):1-13. doi: 10.1007/s00223-010-9360-5. Epub 2010 Apr 29.

  PMID: 20428858 BACKGROUND

• Goldhahn J, Feron JM, Kanis J, Papapoulos S, Reginster JY, Rizzoli R, Dere W, Mitlak B, Tsouderos Y, Boonen S. Implications for fracture healing of current and new osteoporosis treatments: an ESCEO consensus paper. Calcif Tissue Int. 2012 May;90(5):343-53. doi: 10.1007/s00223-012-9587-4. Epub 2012 Mar 28.

  PMID: 22451221 BACKGROUND

• Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, Garcia-Hernandez PA, Recknor CP, Einhorn TA, Dalsky GP, Mitlak BH, Fierlinger A, Lakshmanan MC. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res. 2010 Feb;25(2):404-14. doi: 10.1359/jbmr.090731.

  PMID: 19594305 BACKGROUND

• Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C; ACTIVE Study Investigators. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016 Aug 16;316(7):722-33. doi: 10.1001/jama.2016.11136.

  PMID: 27533157 BACKGROUND

• Bernhardsson M, Aspenberg P. Abaloparatide versus teriparatide: a head to head comparison of effects on fracture healing in mouse models. Acta Orthop. 2018 Dec;89(6):674-677. doi: 10.1080/17453674.2018.1523771. Epub 2018 Oct 18.

  PMID: 30334479 BACKGROUND

• Lanske B, Chandler H, Pierce A, Brown J, Ominsky M, Kostenuik P, Hattersley G. Abaloparatide, a PTH receptor agonist with homology to PTHrP, enhances callus bridging and biomechanical properties in rats with femoral fracture. J Orthop Res. 2019 Apr;37(4):812-820. doi: 10.1002/jor.24254. Epub 2019 Mar 21.

  PMID: 30790359 BACKGROUND

MeSH Terms

Conditions

Hip Fractures

Interventions

abaloparatide

Condition Hierarchy (Ancestors)

Femoral Fractures; Fractures, Bone; Wounds and Injuries; Hip Injuries; Leg Injuries

Study Officials

• Jeri W Nieves, PhD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

• Joseph Lane, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Epidemiology and Senior Research Scientist

Model Details: Parallel assignment with randomization

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 30, 2020
• Study Start: September 17, 2020
• Primary Completion: April 25, 2024
• Study Completion: April 25, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: within one year of study completion
• Access Criteria: A data sharing agreement is required. Dr. Nieves and Dr. Lane will give priority to data sharing requests with the stated purpose of a) Teaching, b) replication or reanalysis of results reported in the primary paper, c) subgroup analyses to be used for the design of future research. Other requests will be considered on a caseby- case basis. Hospital for Special Surgery legal office for research will provide details on their policy.

Locations

US (3)