Fibrodyplasia Ossificans Progressiva (FOP) MedDRA version: 20.0 Level: PT Classification code 10068715 Term: Fibrodysplasia ossificans progressiva System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Saracatinib
Product Code: AZD0530
Pharmaceutical Form: Tablet
INN or Proposed INN: Saracatinib
CAS Number: 893428-72-3
Other descriptive name: SARACATINIB DIFUMARATE
Concentration unit:
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
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-like FOP phenotype by the documentation of an ACVR1R206H/+or variant genomic sequence a. 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. b. 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 pro-cedures such as PET and CT imaging. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 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 weeksafter 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 9%; 8. Significant viral illness or active infections at screening or randomisation; Subjects should not have subacute or acute fevers of >101?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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effectivity of treatment with AZD0530 on HO formation;Secondary Objective: To assess the safety and tolerability of AZD0530 and to further assess effectivity by functional and other radiological/nuclear imaging endpoints;Primary end point(s): 1. The primary endpoint: Primary Safety: Incidence and severity of treatment- emergent adverse events through the end of the Treatment Period 1 at week 26 (RCT) Primary Efficacy: Number of new lesions in the RCT defined as: ?Number of individual new active HO lesions assessed by [18F]-NaF PET at week 26 in placebo vs. drug arms of the RCT* ?Number of individual new HO lesions detected by CT at week 26 in placebo vs. drug arms of the RCT New lesions will be defined by their appearance on sequential [18F]-NaF PET, sequential CT scans, or both. * not related to trauma such as fractures ;Timepoint(s) of evaluation of this end point: The first evaluation will take place after one year of the study. Unblinding of the study will take place after all participants have completed one year of study.All other analyzes will be conducted at the end of the study (after all participants have completed the 18 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints are: 1. The incidence and severity of adverse events (AE) a. During the 6-month RCT b. During 6-month open label extension of AZD0530 2. Number of new lesions after one year of cross-over therapy, defined as: ? 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 pa-tients receiving placebo during the RCT* ? Number of individual new HO lesions detected by CT be-tween the placebo arm at week 26 and the subsequent open-label arm at week 52 among patients receiving pla-cebo during the RCT New lesions will be defined by their appearance on sequential [18F]-NaF PET, sequential CT scans, or both. These cross-over treatment data may be considered separately, or combined with RCT data. * not related to trauma such as fractures 3. Difference in [18F] NaF PET activity of individual active lesion(s) by PET at week 26 between the placebo and drug arms of the RCT, or between the placebo arm at week 26 and its subsequent open label arm at week 52 among cross-over patients. 4. Difference in volume of individual active lesions as assessed by [18F] NaF PET at week 26 between the placebo and drug arm of the RCT, or between the placebo arm at week 26 and its subsequent open label arm at week 52 among cross-over patients. 5. Change in volume of individual HO lesions as assessed by by CT at week 26 between the placebo and drug arm of the RCT, or between the placebo arm at week 26 and its subsequent open label arm at week 52 among cross-over patients. 6. Change in functional mobility outcomes from baseline to week 26 between the place-bo versus drug arm of the RCT, or change between baseline and week 26 in the pla-cebo arm versus the change between week 26 and week 52 among cross-over pa-tients initially treated with placebo in the RCT, as assessed by: a. Change in the cumulative analogue joint involvement scale for FOP (CAJIS), | — |
Countries
Netherlands
Contacts
Public ContactFOP Amsterdam
VU University Medical Center
Outcome results
None listed