Using Saracatinib to Prevent Fibrodysplasia Ossificans Progressiva

Saracatinib Trial TO Prevent FOP

This study is testing if a drug called Saracatinib can help prevent bone growth in people with Fibrodysplasia Ossificans Progressiva.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Amsterdam UMC, location VUmc (Academic / other)
• Locations: 3 sites (Garmisch-Partenkirchen and 2 other locations)
• Trial ID: NCT04307953 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial is a European multicenter, double-blind, randomized controlled trial comparing the effects of AZD0530 (Saracatinib) to a matched placebo in adults diagnosed with Fibrodysplasia Ossificans Progressiva (FOP). Participants will receive either the active drug or placebo for the first 6 months, followed by a 12-month open-label extension where all will receive AZD0530. The study aims to measure changes in heterotopic bone volume using advanced imaging techniques. A total of 20 patients will be enrolled, focusing on those with active disease.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with a confirmed diagnosis of FOP and active disease.

Not a fit: Patients with non-active FOP or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the progression of bone formation in patients with FOP.

How similar studies have performed: While this approach is novel for FOP, similar studies targeting heterotopic ossification have shown promise in other conditions.

Eligibility 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 FOP phenotype by the documentation of an ACVR1R206H/+ or variant 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.

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.

Where this trial is running

Garmisch-Partenkirchen and 2 other locations

• Klinikum Garmish-Partenkirchen — Garmisch-Partenkirchen, Germany (Recruiting)
• Amsterdam University Medical Center — Amsterdam, Netherlands (Recruiting)
• Royal National Orthopaedic Hospital — London, United Kingdom (Not_yet_recruiting)

Study contacts

• Principal investigator: Elisabeth MW Eekhoff, MD, PhD — Amsterdam University Medical Center
• Study coordinator: Vincent A. Verheij, MD

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