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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04307953




Registration number
NCT04307953
Ethics application status
Date submitted
11/03/2020
Date registered
13/03/2020
Date last updated
22/07/2022

Titles & IDs
Public title
Saracatinib Trial TO Prevent FOP
Scientific title
Saracatinib Trial TO Prevent FOP
Secondary ID [1] 0 0
2019-003324-20
Secondary ID [2] 0 0
STOPFOP1
Universal Trial Number (UTN)
Trial acronym
STOPFOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fibrodysplasia Ossificans Progressiva 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD0530 Difumarate
Treatment: Drugs - Matching placebo

Experimental: AZD0530 -

Experimental: Placebo/AZD0530 -


Treatment: Drugs: AZD0530 Difumarate
AZD0530 for the duration of the trial

Treatment: Drugs: Matching placebo
Matching placebo during 6 month RCT, AZD0530 thereafter
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The objective change between the two arms measured in heterotopic bone volume measured by low-dose whole body CT over the initial 6 month RCT
Timepoint [1] 0 0
Baseline, month 6
Secondary outcome [1] 0 0
Safety and tolerability assessments are the incidence and severity of adverse events (AE) during the RCT at the end of week 28.
Timepoint [1] 0 0
Baseline, month 6 (+overall duration study)
Secondary outcome [2] 0 0
The change in heterotopic bone volume measured by low-dose whole body CT over six-months treatment during open-label extension of AZD0530 compared to the previous placebo arm of the RCT
Timepoint [2] 0 0
Baseline, month 6, month 12
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
Baseline, month 6, month 12, month 18
Secondary outcome [4] 0 0
Change in the volume of individual HO lesions
Timepoint [4] 0 0
Baseline, month 6, month 12, month 18
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline, month 6, month 12, month 18
Secondary outcome [6] 0 0
In patients with at least 1 active lesion at baseline: Change (and Area Under the Curve (AUC) analysis) of lesion activity
Timepoint [6] 0 0
Baseline, month 6, month 12
Secondary outcome [7] 0 0
In patients with at least 1 active lesion at baseline: Change in number of active lesion on 18F-NaF PET from baseline to 6 and 12months
Timepoint [7] 0 0
Baseline, month 6, month 12
Secondary outcome [8] 0 0
Change and percent change from baseline in biomarkers of bone formation levels in serum over time.
Timepoint [8] 0 0
Baseline, week 3 through month 18
Secondary outcome [9] 0 0
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 at baseline and month 6, 12 and 18
Timepoint [9] 0 0
baseline, week 3, month 3,6,9,12,and 18
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
baseline, week 3, month 3,6,9,12,and 18
Secondary outcome [11] 0 0
FOP disease activity assessed by movement disabilities and quality of life using FOP Independent Activity of Daily Living (FOP I-ADL)
Timepoint [11] 0 0
baseline, week 3, month 3,6,9,12,and 18
Secondary outcome [12] 0 0
Number of reported flare-ups by the patient
Timepoint [12] 0 0
Each day (day 0-month18)
Secondary outcome [13] 0 0
Pharmacokinetic measurements: blood for determination of plasma concentrations of AZD0530 (pre-dose)on the day of the study visits at 6, 12 and 18months
Timepoint [13] 0 0
6,12 and 18months

Eligibility
Key inclusion criteria
1. 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/+ genomic sequence.

1. 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.

2. 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.

2. 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Not willing to strictly adhere to the reproductive restrictions as defined in section
5.4

2. Women who are pregnant or breast-feeding (from the time 3 months prior to 4 weeks
after completion of participation in the study)

3. 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;

4. Evidence of active bleeding (including hematuria or hematochezia,) acute or chronic
gastrointestinal illness, inflammatory bowel disease, or mucositis

5. Malignant disease / cancer requiring treatment in the past 3 years (except some
primary non melanoma skin cancer);

6. 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;

7. Showing uncontrolled diabetes mellitus with an HbA1C > 9%;

8. 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

9. Evidence of prolonged QT interval at screening or randomization (defined as QTc of
>450 ms) .or known congenital long-QT syndrome.

10. Neutropenia defined as an absolute neutrophil count of <1,500/µl,

11. Thrombocytopenia defined as platelet count <100 × 103/µl,

12. 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.-

13. 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;

14. Known allergy or intolerance to AZD0530 or any excipients used in the investigational
medicinal products.

15. 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.

16. Treatment with another investigational or drug that might interfere with HO formation
and the interpretation of the study drug in the last 90 days

17. 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.

18. Currently active metabolic bone disease, other than FOP.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2024
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Garmisch-Partenkirchen
Country [2] 0 0
Netherlands
State/province [2] 0 0
Amsterdam
Country [3] 0 0
United Kingdom
State/province [3] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Amsterdam UMC, location VUmc
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal National Orthopaedic Hospital NHS Trust
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Klinikum Garmisch-Patenkirchen
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Oxford
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Brigham and Women's Hospital
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Commercial sector/Industry
Name [5] 0 0
AstraZeneca
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Innovative Medicines Initiative
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.

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.

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 objective change in heterotopic bone volume measured by low-dose
whole-body computer tomography (CT) , [18F] NaF Positron Emission Tomography (PET) activity
and patient reported outcome measures.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04307953
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Elisabeth MW Eekhoff, MD, PhD
Address 0 0
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bernard J Smilde, MD
Address 0 0
Country 0 0
Phone 0 0
+31204444444
Fax 0 0
Email 0 0
b.smilde@amsterdamumc.nl
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04307953