Fibrodysplasia Ossificans ProgressivaPhase 2STOPFOPNCT04307953
Saracatinib Trial TO Prevent FOP
A Phase 2 study testing AZD0530 Difumarate in people with Fibrodysplasia Ossificans Progressiva, run by Amsterdam UMC, location VUmc at 3 sites in 3 countries.
Trial summary
This is a phase 2 study, designed as a European multicentre 6-month double blind random-ized controlled trial (RCT) of AZD0530 versus matched placebo, followed by a 12 month trial comparing open-label extended AZD0530 treatment with historical control data. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Fibrodysplasia Ossificans Progressiva
- What is being tested?
- AZD0530 Difumarate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 5 Aug 2020to 30 Nov 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged 18-65 with a clinical diagnosis of FOP at screening, including congenital malformation of the great toes and a history of spontaneous or injury-induced heterotopic ossification (HO), and have a confirmed classic FOP phenotype by the documentation of an ACVR1R206H/+ or variant genomic sequence.
- Female participants who are women of child-bearing potential will be required to use a highly effective method of contraception as defined in section 5.4, in combination with a condom or diaphragm or cervical/vault caps with spermicidal foam/gel/film/suppository), from the time of enrolment until 4 weeks after final dose of study drug, unless practicing true sexual abstinence as defined in section 5.4.
- Male participants will be required to avoid procreative sexual intercourse with women of child-bearing potential from time of enrollment until 4 weeks after final dose of study drug through use of highly effective contraceptive methods. Male participants with a pregnant female partner will be required to use a condom for the duration of the study and for 4 weeks final dose of study drug. Male study participants will not be permitted to donate sperm for from the time of enrolment and until 4 weeks after final dose of study drug.
- Participants will have to be able to understand and complete study and willing to sign informed consent (IC). They have to be able to attend and comply with the study visits and related activities, adhere to all study-related restrictions, and able to undergo procedures such as PET and CT imaging.
Who cannot join
- Not willing to strictly adhere to the reproductive restrictions as defined in section 5.4
- Women who are pregnant or breast-feeding (from the time 3 months prior to 4 weeks after completion of participation in the study)
- The presence of significant concomitant illness or history of significant illness such as cardiac, respiratory, renal, rheumatologic, neurologic, psychiatric, endocrine, metabolic, lymphatic disease, or infectious disease, that might confound the results of the study or pose additional risk to the patient;
- Evidence of active bleeding (including hematuria or hematochezia,) acute or chronic gastrointestinal illness, inflammatory bowel disease, or mucositis
- Malignant disease / cancer requiring treatment in the past 3 years (except some primary non melanoma skin cancer);
- Severely impaired renal function defined as estimated glomerular filtration rate <30 mL/min/1.73 m2 calculated by the Modification of Diet in Renal Disease equation;
Show all 18Show fewer
- Showing uncontrolled diabetes mellitus with an HbA1C > 9%;
- Significant viral illness or active infections at screening or randomisation; Subjects should not have subacute or acute fevers of >101 degrees F at time of screening or randomisation
- Evidence of prolonged QT interval at screening or randomization (defined as QTc of >450 ms) .or known congenital long-QT syndrome.
- Neutropenia defined as an absolute neutrophil count of <1,500/µl,
- Thrombocytopenia defined as platelet count <100 × 103/µl,
- Current blood clotting or bleeding disorder, or significantly abnormal INR-prothrombin time or partial thromboplastin time at screening, or clinically significant abnormalities in other screening laboratories, including significant abnormalities in vitamin B12 or thyroid function tests would be cause for exclusion.-
- Abnormal liver function test results defined as aspartate aminotransferase (AST) >2.0 x upper limit of normal (ULN); alanine aminotransferase (ALT) >2.0 x ULN; and / or total bilirubin >1.5 x ULN;
- Known allergy or intolerance to AZD0530 or any excipients used in the investigational medicinal products.
- Simultaneous participation in another interventional clinical study or a non-interventional study with imaging measures or invasive procedures (eg. collection of blood or tissue samples); Participation in the FOP Connection Registry (www.fopconnection.org) or other studies in which patients completed study questionnaires are possible.
- Treatment with another investigational or drug that might interfere with HO formation and the interpretation of the study drug in the last 90 days
- Current use or history of regular alcohol consumption exceeding 14 units/week (6 glasses of 13.0% wine (175ml), 6 pints of 4.0% lager or ale (568ml), 5 pints of 4.5% cider (568 ml) or 14 glasses of 10.0% spirits (25ml)) within 6 months of screening.
- Currently active metabolic bone disease, other than FOP.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United Kingdom1 site
Royal National Orthopaedic Hospital
London, HA7 4LP
About this study
This is a phase 2 study, designed as a European multicentre 6-month double blind random-ized controlled trial (RCT) of AZD0530 versus matched placebo, followed by a 12 month trial comparing open-label extended AZD0530 treatment with historical control data.
Study population: Male and female adult patients aged 18 years and older with a diagnosis of FOP who meet the inclusion (active disease) and exclusion criteria will be eligible for participation in this study. The total number of enrolled patients will be 20.
Read more
Intervention: Patients will be randomized to receive either AZD0530 100mg once daily or matched placebo, taken orally for the first 6 months, immediately followed by an open-label extension in which all patients will receive AZD0530 100mg once daily oral dose for a further 12 months.
Endpoints: Endpoints include change in number of active heterotopic bone lesions measured by low-dose whole-body computer tomography (CT)/ [18F] NaF Positron Emission Tomography (PET) activity
- Conditions
- Fibrodysplasia Ossificans Progressiva
- Being tested
- AZD0530 Difumarate, Matching placebo
- Keywords
- Fibrodysplasia Ossificans Progressiva, AZD0530, Saracatinib, Stone man syndrome, FOP
- Medical subject headings
- Myositis Ossificans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0530 DifumarateDrug
Also called Saracatinib
AZD0530 for the duration of the trial
Matching placeboDrug
Matching placebo during 6 month RCT, AZD0530 thereafter
| Study group | Role | What they receive |
|---|---|---|
| AZD0530 | Experimental | Not described Receives: Drug: AZD0530 Difumarate |
| Placebo/AZD0530 | Experimental | Not described Receives: Drug: Matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of new active HO lesions on [18F] NaF PET/ CT
The change between the two arms in development of new active heterotopic bone lesions measured by [18F] NaF PET/low-dose whole body CT during the initial 6-month RCT
Measured: Baseline, month 6
Secondary outcomes (13)
Safety and tolerability assessments are the incidence and severity of adverse events (AE) during the RCT at the end of week 26.
Measured: Baseline, month 6 (+overall duration study)
New active HO lesions of the placebo arm during 26 weeks RCT compared to its roll over to 26-week open label treatment
Number of individual new active HO lesions assessed by [18F]-NaF PET between the placebo arm at week 26 and the subsequent open-label phase at week 52 among patients receiving placebo during the RCT
Measured: Baseline, month 6, month 12
The change in heterotopic bone volume measured by low-dose whole body CT over twelve-months treatment during open-label extension of AZD0530 compared to the historical data of Clementia (NCT02322255)
Measured: Baseline, month 6, month 12, month 18
Change in the volume of individual HO lesions
measured by low-dose whole body CT over the initial 6 month RCT and the change over twelve-months therapy during open-label extension of AZD0530 compared to the historical data of Clementia and compared to the 6 months placebo-arm.
Measured: Baseline, month 6, month 12, month 18
Change in number of HO lesions measured by CT over the initial 6 month RCT and in addition the change over twelve-months during open-label extension of AZD0530 compared to the historical data of Clementia and compared to the 6 months placebo-arm.
Measured: Baseline, month 6, month 12, month 18
In patients follow-up of lesion activity
by 18F-NaF PET over the initial 6 month RCT and over months 6-12 compared to the 6 months RCT of the placebo arm, including change from baseline in 18F-NaF Standard Uptake Volume (SUVmean or peak) of individual active HO sites up to most active seven lesions.
Measured: Baseline, month 6, month 12
Follow-up of HO growth
Follow-up up to 7 most active HO lesion identified at CT at baseline: Change in volume from baseline to 6 for comparion in RCT en at 12 months for compariosn placebo RCT with its switch over
Measured: Baseline, month 6, month 12
Change and percent change from baseline in biomarkers of bone formation levels in serum over time.
Including Total Procollagen Type 1 N-Terminal Propeptide (P1NP), Alkaline Phosphatase (AP) fasting cross-linked C-terminal telopeptide of type I colla-gen (βCTX). Selected genetic markers for FOP activity
Measured: Baseline, week 3 through month 18
Joint function assessment by physician at baseline and week 3, month 3,6,9,12,and18 by the cumulative analog joint involvement scale (CAJIS) and the quantitative detailed multi-joint assessment and mounth at baseline and month 6, 12 and 18
Measured: baseline, week 3, month 3,6,9,12,and 18
Patient-reported global health status the 36-item Short Form Health Survey (SF-36) at baseline and week 3, month 3,6,9,12,and 18
Measured: baseline, week 3, month 3,6,9,12,and 18
FOP disease activity assessed by movement disabilities and quality of life using FOP Independent Activity of Daily Living (FOP I-ADL)
Measured: baseline, week 3, month 3,6,9,12,and 18
Number of patient reported and investigator confirmed flare-ups
Measured: Each day (day 0-month18)
Pharmacokinetic measurements: blood for determination of plasma concentrations of AZD0530 (pre-dose)on the day of the study visits at 6, 12 and 18months
Measured: 6,12 and 18months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2020
- Study start5 Aug 2020
- Primary completion30 Nov 2025
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fibrodysplasia Ossificans ProgressivaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 6-month double blind randomized controlled trial of AZD0530 versus placebo, followed by a 12 month open label extension phase
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Royal National Orthopaedic Hospital NHS Trust, Klinikum Garmisch-Patenkirchen, University of Oxford, Brigham and Women's Hospital, AstraZeneca, Innovative Medicines Initiative
- Responsible party
- Principal investigator, Elisabeth MW Eekhoff, Amsterdam UMC, location VUmc
- Investigators
- Elisabeth MW Eekhoff, MD, PhD, Principal investigator, Amsterdam University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04307953
- Sponsor's protocol ID
- STOPFOP1
- Other IDs
- 2019-003324-20, NL71401.029.19, CTIS, 2019
- Acronym
- STOPFOP
- Status last verified
- Aug 2026
- First submitted
- 11 Mar 2020
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Smilde BJ, Stockklausner C, Keen R, Whittaker A, Bullock AN, von Delft A, van Schoor NM, Yu PB, Eekhoff EMW. Protocol paper: a multi-center, double-blinded, randomized, 6-month, placebo-controlled study followed by 12-month open label extension to evaluate the safety and efficacy of Saracatinib in Fibrodysplasia Ossificans Progressiva (STOPFOP). BMC Musculoskelet Disord. 2022 Jun 1;23(1):519. doi: 10.1186/s12891-022-05471-x.
PubMed 35650602