Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
360
Countries
4
Sites
4
Osteogenesis imperfecta
To determine if a two year spell of treatment with a drug called teriparatide (TPTD), followed by treatment with zoledronic acid (ZA) reduces the proportion of participants experiencing a broken bone (fracture) which has been confirmed by x-ray or other imaging. The effects of TPTD/ZA will be compared with standard car…
Key facts
- Sponsor
- University Of Edinburgh, NHS Lothian
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]
- Trial duration
- 26 Mar 2019 → 21 Mar 2025
- Decision date (initial)
- 2025-01-02
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-519705-36-00
- EudraCT number
- 2016-003228-22
- ISRCTN
- ISRCTN15313991
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Pharmacogenetic, Safety, Prophylaxis
To determine if a two year spell of treatment with a drug called teriparatide (TPTD), followed by treatment with zoledronic acid (ZA) reduces the proportion of participants experiencing a broken bone (fracture) which has been confirmed by x-ray or other imaging. The effects of TPTD/ZA will be compared with standard care which may consist of no active treatment of treatment or treatment with a class of drugs called bisphosphonates depending on the preference of the patient and their normal care provider.
Secondary objectives 1
- To compare the effects of TPTD/ZA and standard care on the total number of fractures experienced by participants, the number of spine fractures and to determine if treatments differ in their effects on bone pain assessed by the brief pain inventory (BPI); quality of life as assessed by the SF36 questionnaire; sleep quality assessment questionnaire (PQSI); and functional status as assessed by the health assessment questionnaire (HAQ) and EuroQol5D (EQ5D) assessment tools. The trial will also evaluate the relationship between patient demographics, clinical features of OI, bone density values at baseline, type of genetic mutation and biochemical markers of bone turnover and fracture occurrence OI and the response to treatment
Conditions and MedDRA coding
Osteogenesis imperfecta
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Adult patients age 18 years and above with a clinical diagnosis of OI
- Patients willing and able to consent and comply with the study protocol
Exclusion criteria 6
- Current or previous treatment with an investigational (non-licensed) drug with effects on bone metabolism within two years of screening or treatment with teriparatide within two years of screening
- Contraindication to TPTD or ZA
- Women of childbearing potential not using highly effective methods of contraception (see below). Women of childbearing potential (WOCBP) can be enrolled into the study but will be required to use highly effective methods of contraception (as defined by the HMA Clinical Trial Facilitation Group recommendations) before, during the trial if they are being treated with TPTD or bisphosphonates. Examples of highly effective contraception include: • Established use of oral, injected or implanted hormonal methods of contraception. • Placement of an intrauterine device (IUD) or intrauterine system (IUS). • Bilateral tubal occlusion • Vasectomised partner True abstinence. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Barrier methods of contraception (condom or occlusive cap (diaphragm or cervical/vault caps with or without spermicidal foam/gel/film/cream/suppository) are not considered to be highly effective methods of contraception
- Pregnancy
- Women that are breastfeeding
- Age <18 years
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- The proportion of participants experiencing a clinical fracture validated by x-ray or other imaging
- This is an event driven study which will be terminated when 139 participants have experienced an incident clinical fracture validated by x-ray or other imaging. This is expected to have occurred after an average of 62 months follow up.
Secondary endpoints 6
- The total number of clinical fractures experienced by participants validated by x-ray or other imaging.
- The number of incident vertebral fractures assessed by imaging of the thoracic and lumbar spine.
- The total number of fractures experienced by participants defined as the combination validated clinical fractures and vertebral fractures and fractures reported by participants, where imaging was not performed, not feasible or where the results were inconclusive.
- Bone pain assessed by the brief pain inventory (BPI); quality of life as assessed by the SF36 questionnaire; functional status as assessed by the health assessment questionnaire (HAQ) and EuroQol5D (EQ5D) assessment tools, and adverse events
- The total number of clinical fractures validated by imaging, incident vertebral fractures, and total number of fractures will be evaluated at the same time as the primary endpoint which on average will be after an average duration of 62 months follow up
- Bone pain, health related quality of life and functional status will be evaluated after 12 months, 24 months and at the end of study (approximately 62 months)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
FORSTEO 20 micrograms/80 microliters solution for injection in pre-filled pen
PRD2559502 · Product
- Active substance
- Teriparatide
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 20 µg microgram(s)
- Max total dose
- 20 µg microgram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- H05AA02 — TERIPARATIDE
- Marketing authorisation
- EU/1/03/247/001
- MA holder
- ELI LILLY NEDERLAND B.V.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The IMP is not licensed for osteogenesis imperfecta but is sometimes used for this indication. Reduced labelling applied.
Zoledronic Acid Seacross 5 mg/100ml solution for infusion
PRD6840573 · Product
- Active substance
- Zoledronic Acid Monohydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- SOLUTION FOR INFUSION
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- M05BA08 — ZOLEDRONIC ACID
- Marketing authorisation
- PL 41013/0012
- MA holder
- SEACROSS PHARMACEUTICALS LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Zoledronic acid is not licensed for osteogenesis imperfecta but is sometimes used off label for this indication.
Comparator 9
Risedronate Sodium 35 mg Film-coated Tablets
PRD759807 · Product
- Active substance
- Risedronate Sodium
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0 mg/g milligram(s)/gram
- Max total dose
- 35 mg/g milligram(s)/gram
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BA07 — RISEDRONIC ACID
- Marketing authorisation
- PL 04416/1165
- MA holder
- SANDOZ LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Risedronate is not licensed for the treatment of osteogenesis imperfecta but is widely used for this indication.
Prolia 60 mg solution for injection in pre-filled syringe
PRD3618669 · Product
- Active substance
- Denosumab
- Substance synonyms
- AMG 162, HLX14, TVB-009, MAB-22
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 0 mg/ml milligram(s)/millilitre
- Max total dose
- 60 mg/ml milligram(s)/millilitre
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BX04 — -
- Marketing authorisation
- EU/1/10/618/001
- MA holder
- AMGEN EUROPE B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- rolia is not licensed for the treatment of osteogenesis imperfecta but is widely used for this indication.
PRD10069306 · Product
- Active substance
- Clodronate Disodium
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 1600 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BA02 — CLODRONIC ACID
- Marketing authorisation
- PL 51463/0091
- MA holder
- KENT PHARMA UK LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Clasteon sodium clondronate is not licensed for the treatment of osteogenesis imperfecta but is widely used for this indication.
PRD302541 · Product
- Active substance
- Alendronate Sodium Trihydrate
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0 mg/g milligram(s)/gram
- Max total dose
- 70 mg/g milligram(s)/gram
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BA04 — ALENDRONIC ACID
- Marketing authorisation
- PL 16363/0310
- MA holder
- MILPHARM LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Alendronic acid is not licensed for osteogenesis imperfecta, but is widely used clinically for this indication.
Calcichew-D3 500 mg/200 IU Chewable Tablet
PRD9156739 · Product
- Active substance
- Colecalciferol
- Pharmaceutical form
- CHEWABLE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 500 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- A12AX — CALCIUM, COMBINATIONS WITH OTHER DRUGS
- Marketing authorisation
- PL 45043/0084
- MA holder
- NEON HEALTHCARE LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The IMP is not licensed for osteogenesis imperfecta but is sometimes used for this indication.
PRD1691381 · Product
- Active substance
- Colecalciferol
- Substance synonyms
- CHOLECALCIFEROL, VITAMIN D3, COLECALCIPHEROL
- Pharmaceutical form
- CAPSULE, SOFT
- Route of administration
- ORAL USE
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 800 IU international unit(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- A11CC05 — COLECALCIFEROL
- Marketing authorisation
- PL 40861/0002
- MA holder
- INTERNIS PHARMACEUTICALS LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Not licensed for osteogenesis imperfecta but often used for this indication
Ibandronic acid Accord 3 mg solution for injection in pre-filled syringe
PRD2997826 · Product
- Active substance
- Ibandronic Acid
- Substance synonyms
- IBANDRONATE, BONDRONAT
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 3 mg milligram(s)
- Max total dose
- 3 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BA06 — IBANDRONIC ACID
- Marketing authorisation
- EU/1/12/798/005
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Ibandronic acid is not licensed for the treatment of osteogenesis imperfecta but is widely used for this indication.
Ibandronic acid Sandoz 150 mg Film-coated Tablets
PRD755102 · Product
- Active substance
- Sodium Ibandronate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 150 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BA06 — IBANDRONIC ACID
- Marketing authorisation
- PL 04416/1200
- MA holder
- SANDOZ LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Ibandronic acid is not licensed for the treatment of osteogenesis imperfecta but is widely used for this indication.
Disodium Pamidronate 15mg/ml Concentrate for Solution for Infusion
PRD994044 · Product
- Active substance
- Pamidronate Disodium
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- SOLUTION FOR INFUSION
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 15 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- M05BA03 — PAMIDRONIC ACID
- Marketing authorisation
- PL 29831/0071
- MA holder
- WOCKHARDT UK LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Disodium Pamidronate is not licensed for the treatment of osteogenesis imperfecta but is widely used for this indication.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
University Of Edinburgh
- Sponsor organisation
- University Of Edinburgh
- Address
- 47 Little France Crescent, Bioquarter Bioquarter
- City
- Edinburgh
- Postcode
- EH16 4TJ
- Country
- United Kingdom
Scientific contact point
- Organisation
- University Of Edinburgh
- Contact name
- Fiach O'Mahony
Public contact point
- Organisation
- University Of Edinburgh
- Contact name
- Fiach O'Mahony
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Aarhus University Hospital ORG-100052990
|
Aarhus N, Denmark | On site monitoring |
NHS Lothian
- Sponsor organisation
- NHS Lothian
- Address
- 2a Chalmers Street
- City
- Edinburgh
- Postcode
- EH3 9ES
- Country
- United Kingdom
Sponsor responsibilities
- Article 77 compliance
- University Of Edinburgh
- Contact point sponsor
- University Of Edinburgh
- Article 77 implementation
- University Of Edinburgh
Locations
4 EU/EEA countries · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ended | 18 | 1 |
| France | Ended | 10 | 1 |
| Ireland | Ended | 10 | 1 |
| Netherlands | Ended | 19 | 1 |
| Rest of world
United Kingdom
|
— | 303 | — |
Investigational sites
Aarhus University Hospital
Clinical Medicine – Endocrinology and Metabolism, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Hôpital Lariboisiere
Department of Rheumatology, 2 rue Ambroise Paré, Maladies Infectieuses et Tropicales, Paris
St Vincent's University Hospital
Consultant Physician, Nutley Lane Donnybrook, Elm Park, Dublin 4
Amsterdam University Medical Center, VUmc Boelelaan
Endocrinology, De Boelelaan 1117, 1081 HV, Amsterdam
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2022-11-03 | 2025-03-21 | 2022-11-07 | 2024-11-30 | |
| France | 2021-11-29 | 2025-03-21 | 2022-02-10 | 2024-12-02 | |
| Ireland | 2019-03-26 | 2025-03-21 | 2019-04-17 | 2024-11-19 | |
| Netherlands | 2021-11-29 | 2025-03-21 | 2022-01-20 | 2024-11-30 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| ToPAZ ISRCTN Final Report SUM-128635
|
2026-04-13T11:03:40 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| ToPAZ Lay Person Summary of Results | 2026-04-13T11:03:09 | Submitted | Laypersons Summary of Results |
Documents 26 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Lay summary of Study results_Final_03Mar2026 | 1 |
| Protocol (for publication) | D1_TOPaZ Protocol 2024-519705-36-00 | 12.0 |
| Recruitment arrangements (for publication) | Placeholder Document | 1 |
| Recruitment arrangements (for publication) | Placeholder Document | 1 |
| Recruitment arrangements (for publication) | Placeholder Document | 1 |
| Recruitment arrangements (for publication) | Placeholder Document | 1 |
| Subject information and informed consent form (for publication) | PIL ICF | 7.0 |
| Subject information and informed consent form (for publication) | TOPaZ Consent | 7.0 |
| Subject information and informed consent form (for publication) | TOPaZ Consent | 7.0 |
| Subject information and informed consent form (for publication) | TOPaZ FR Consent | 7.0 |
| Subject information and informed consent form (for publication) | TOPaZ PIL | 7.0 |
| Subject information and informed consent form (for publication) | TOPAZ PIL | 7.0 |
| Subject information and informed consent form (for publication) | TOPaZ PIL | 7.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Forsteo 20 micrograms_80 microlitres solution EU | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Alendronic Acid 70 mg tablets PL163630310 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Calcichew D3 500 mg Chewable Tablets PL450430084 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Clasteon Sodium Clodronate 400mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Disodium Pamidronate 15mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Fultium-D3 800IU capsules | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Ibandronic acid 150mg tablets | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Ibandronic acid 3 mg soln UK | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Ibandronic acid 3mg Solution | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Prolia 60mg solution_EU sites_denosumab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Risedronate Sodium 35mgTablets PL044161165 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Zoledronic Acid 5 mg_100ml PL410130012 | 1 |
| Summary of results (for publication) | ISRCTN final report_13Mar2026 | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-11-18 | Ireland | Acceptable 2024-12-17
|
2024-12-17 |