Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid

NCT03735537 | Completed Phase 4 DMC

• 2 other identifiers: AC160922016-003228-22
• Study Type: interventional
• Target: 350
• Locations: 2 countries
• Sites: 23

Brief Summary

Osteogenesis imperfecta (OI) is an inherited skeletal disorder characterised by increased risk of fragility fractures. Bisphosphonates are frequently prescribed for adult patients with OI with the aim of preventing fractures but the evidence base for efficacy is poor. Recent evidence suggests that the bone anabolic agent teriparatide (TPTD) increases bone mineral density (BMD) and may have the potential to prevent fractures in OI. The purpose of the TOPaZ Trial is to investigate if a a two-year course of teriparatide (TPTD) followed by antiresorptive therapy with a single infusion of zoledronic acid (ZA) in adults with OI reduces the proportion of patients who experience a fracture as compared with standard care Adult patients with a clinical diagnosis of OI who are willing and able to give informed consent and who do not have contraindications to the study medications will be recruited from participating sites. Participants will be randomised 1:1 to receive either standard care for the duration of the trial or TPTD for 24 months followed by a single infusion of ZA, or another antiresorptive agent in the event that ZA is contraindicated. Participants will attend recruiting centres for a Baseline/Screening visit, at 12 months, 24 months and at the end of the trial for formal study visits with telephone calls every 6 months from a site research nurse. Participants randomised to TPTD will also attend recruiting centre at regular intervals during the 24 month treatment period to collect new supplies of TPTD.

Conditions

Osteogenesis Imperfecta

Keywords

Fracture; Teriparatide

Outcome Measures

Primary Outcomes (1)

• Incident clinical fractures validated by x-ray or other imaging

  Proportion of participants experiencing a clinical fracture validated by x-ray or other imaging as compared to standard care

  Through study completion, approximately 5 years

Secondary Outcomes (8)

• Total number of incident vertebral fractures

  Baseline (0) and Final Trial Visit (5 years after baseline)

• Total number of fractures

  Through study completion, approximately 5 years

• Pain assessed by the Brief Pain Inventory (BPI) Short Form measure

  Baseline (0), 12 months, 24 months and Final Trial Visit (5 years after baseline)

• Quality of life assessed by the SF-36 (v1) Quality of Life

  Baseline, 12 months, 24 months and Final Trial Visit (5 years after baseline

• Sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) measure

  Baseline (0), 12 months, 24 months and Final Trial Visit (5 years after baseline)

Study Arms (2)

Teriparatide and zoledronic acid

ACTIVE COMPARATOR

Teriparatide (TPTD) 20mcg daily using Teriparatide Pen Injector, given subcutaneously using a self-administered injection device for two years (24 months) followed by a single intravenous 5mg infusion of zoledronic acid.

Drug: Teriparatide Pen Injector; Drug: Zoledronic Acid

Standard Care

NO INTERVENTION

Continuation of existing bone modifying treatment (i.e. bisphosphonate treatment) or no active bone modifying treatment according to the clinical judgement of the local investigator.

Interventions

Teriparatide Pen Injector DRUG

Also known as: Forsteo, Forteo

Teriparatide and zoledronic acid

Zoledronic Acid DRUG

Any brand or preparation may be used to deliver the required dose of 5mg

Also known as: Aclasta 5mg solution for infusion, Zoledronic acid 5mg/100ml solution for infusion

Teriparatide and zoledronic acid

Eligibility Criteria

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

You may qualify if:

• Adult patients aged 18 years and over with a clinical diagnosis of Osteogenesis Imperfecta (OI)
• Patients willing and able to consent and comply with the study protocol

You may not qualify if:

• Current or previous treatment with an investigational (non-licensed experimental) drug with effects on bone metabolism
• Contraindication to teriparatide or zoledronic acid
• Women of childbearing potential not using highly effective methods of contraception
• Pregnancy
• Women that are breastfeeding
• Age \< 18 years

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (23)

St Vincent's Hospital

Dublin, 4, Ireland

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZR, United Kingdom

Location

Royal Victoria Hospital

Belfast, BT12 6BA, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Bristol Royal Infirmary

Bristol, NS2 8HW, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Royal Liverpool Hospital and Aintree Hospital

Liverpool, L7 8XP, United Kingdom

Location

Llandough University Hospital

Llandough, CF64 2XX, United Kingdom

Location

Guy's and St Thomas' Hospital

London, SE1 9RT, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

James Cook University Hospital

Middlesbrough, PS4 3BW, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PD, United Kingdom

Location

Nuffield Orthopaedic Centre

Oxford, OX3 7HE, United Kingdom

Location

Northern General Hospital

Sheffield, S5 7AU, United Kingdom

Location

University Hospital Southampton

Southampton, S016 6YD, United Kingdom

Location

Royal National Orthopaedic Hospital

Stanmore, HA7 4LP, United Kingdom

Location

Haywood Community Hospital

Stoke-on-Trent, ST6 7AG, United Kingdom

Location

Wishaw General Hospital

Wishaw, ML2 0DP, United Kingdom

Location

Related Links

• Trial webpage

MeSH Terms

Conditions

Osteogenesis Imperfecta; Fractures, Bone

Interventions

Teriparatide; Zoledronic Acid; Solutions

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations

Study Officials

• Stuart Ralston, MD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Images of incident fractures and vertebral fractures will be assessed by an independent clinical adjudicator blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre, parallel arm, open-label, phase IV randomised controlled trial

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: November 8, 2018
• Study Start: November 1, 2016
• Primary Completion: February 28, 2025
• Study Completion: March 21, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1); GB (22)