Saracatinib Trial TO Prevent FOP

NCT04307953 | Recruiting Phase 2 DMC

• 3 other identifiers: STOPFOP12019-003324-20NL71401.029.19
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 3

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.

Conditions

Fibrodysplasia Ossificans Progressiva

Keywords

Fibrodysplasia Ossificans Progressiva; AZD0530; Saracatinib; Stone man syndrome; FOP

Outcome Measures

Primary Outcomes (1)

• 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

  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 28.

  Baseline, month 6 (+overall duration study)

• 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

  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)

  Baseline, month 6, month 12, month 18

• Change in the volume of individual HO lesions

  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.

  Baseline, month 6, month 12, month 18

Study Arms (2)

AZD0530

EXPERIMENTAL

Drug: AZD0530 Difumarate

Placebo/AZD0530

EXPERIMENTAL

Drug: Matching placebo

Interventions

AZD0530 Difumarate DRUG

AZD0530 for the duration of the trial

Also known as: Saracatinib

AZD0530

Matching placebo DRUG

Matching placebo during 6 month RCT, AZD0530 thereafter

Placebo/AZD0530

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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,
• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Royal National Orthopaedic Hospital NHS Trust: collaborator
• Klinikum Garmisch-Patenkirchen: collaborator
• University of Oxford: collaborator
• Brigham and Women's Hospital: collaborator
• AstraZeneca: collaborator
• Innovative Medicines Initiative: collaborator

Study Sites (3)

Klinikum Garmish-Partenkirchen

Garmisch-Partenkirchen, 82467, Germany

RECRUITING

Amsterdam University Medical Center

Amsterdam, 1081HV, Netherlands

RECRUITING

Royal National Orthopaedic Hospital

London, HA7 4LP, United Kingdom

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 35650602 DERIVED

MeSH Terms

Conditions

Myositis Ossificans

Interventions

saracatinib

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases

Study Officials

• Elisabeth MW Eekhoff, MD, PhD

  Amsterdam University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent A. Verheij, MD

CONTACT

+31204444444; v.a.verheij@amsterdamumc.nl

Elisabeth MW Eekhoff, MD, PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Principal Investigator

Model Details: 6-month double blind randomized controlled trial of AZD0530 versus placebo, followed by a 12 month open label extension phase

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 13, 2020
• Study Start: August 5, 2020
• Primary Completion: May 6, 2025
• Study Completion: May 6, 2025
• Last Updated: May 3, 2024

Record last verified: 2024-04

Locations

GB (1); DE (1); NL (1)