Clinical Trials

Inclusion Criteria:

• Male or female subjects, 18 to 60 years of age at screening.
• Clinical diagnosis of FOP (based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive HO).
• Confirmation of FOP diagnosis with documentation of any ACVR1 mutation.
• FOP disease activity within 1 year of screening visit. FOP disease activity is defined as pain, swelling, stiffness, and other signs and symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of HOs (increase in size or number of HO lesions) with/without being associated with flare-up episodes.
• Provide signed informed consent.
• Willing and able to attend and comply with study visits and study related activities.
• Willing and able to undergo PET and CT imaging procedures and other procedures as defined in this study.
• Able to understand and complete study-related questionnaires and diaries (assistance
• from caregivers are allowed).

Exclusion Criteria:

• Patient has significant concomitant illness or history of significant illness such as, but not limited to cardiac, renal, rheumatologic, neurologic, psychiatric, endocrine, metabolic or lymphatic disease, that in the opinion of the study investigator might confound the results of the study or pose additional risk to the patient by their participation in the study.
• Previous history or diagnosis of 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 (1 retest is allowed).
• Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening (1 retest allowed).
• Cardiovascular conditions such as New York Heart Association class III or IV heart failure, cardiomyopathy, intermittent claudication, myocardial infarction, or acute coronary syndrome within 6 months prior to screening; symptomatic ventricular cardiac arrhythmia (note: sinus dysrhythmia, asymptomatic block or well controlled atrial fibrillation with normal resting ventricular rate are not exclusion criteria).
• Ongoing significant viral illness or pneumonia within 2 weeks of screening.
• Severe anemia requiring transfusion.  History of severe respiratory compromise requiring oxygen, respiratory support (example bilevel positive airway pressure [biPAP] or continuous positive airway pressure [CPAP]) or a history of aspiration pneumonia requiring hospitalization.
• Known history of recent epididymitis (within 6 months of screening), TB, or sexually transmitted diseases affecting urogenital organs.
• Use of bisphosphonate within 1 year of screening.
• Concurrent participation in another interventional clinical study or a non-interventional study with radiographic measures or invasive procedures (eg, collection of blood or tissue samples). Participation in the FOP Connection Registry or other studies in which patients complete study questionnaires are allowed.
• Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer.
• History of hypersensitivity to doxycycline or other tetracycline antibiotics, vaccines, or other biologics.
• Positive serum human chorionic gonadotropin (hCG)/urine pregnancy test at the screening/baseline visit.
• Pregnant or breastfeeding women.
• Women of child bearing potential* who are unwilling to practice highly effective contraception** or undergo pregnancy tests prior to the initial dose, during the study, and for 30 weeks after the last dose.
  • * Pregnancy testing and contraception are not required for women not of child bearing potential, including postmenopausal women or those with documented hysterectomy or bilateral oophorectomy.
  • Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Postmenopausal status will be confirmed by measurement of FSH.
  • ** Highly effective contraceptive measures include stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; intrauterine device (IUD); intrauterine hormone-releasing system (IUS);
  • bilateral tubal ligation; vasectomized partner; and or sexual abstinence***.
  • *** Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.
• Male patients with WoCBP partners* who are not willing to use condoms with WoCBP partners to prevent potential fetal exposure, during the study, and for 24 weeks after the last dose. Sperm donation is prohibited during the study and for 24 weeks after the last dose of study drug.
  • * Male patients with WoCBP partners will be asked to inform and ensure their female partners to use highly effective contraception measures** to prevent pregnancy.
  • ** Vasectomy with medical assessment of surgical success and sexual abstinence*** are considered highly effective contraception measures.
  • *** Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.