Inclusion Criteria:

• Informed consent/assent:
  • For adult participants (≥ 18 years of age), ability to comprehend and willingness to sign an ICF;
  • For adolescent participants (≥ 12 to < 18 years of age), written informed consent of the parent(s) or legal guardian and written assent from the adolescent participant.
    • Note: Adolescents who during the course of the study become legal adults will be asked for their consent to participate in the study.
• Female and male adults and adolescents ≥ 12 years of age.
• Clinical diagnosis of FOP (based on findings of congenital malformation of the great toes, episodic soft-tissue swelling, and/or progressive HO).
• Participant-reported FOP disease activity within 1 year of the screening visit. This is defined as pain, swelling, and other signs and symptoms associated with FOP flare-ups or wosening of joint function or radiographic progression of HO (increase in site or number of HO lesions) with or without an association with flare-up episodes.
• Ability to swallow and retain orally administered tablets, either whole or crushed and dispersed in foods or liquids.
• Willingness to avoid pregnancy or fathering children based on the criteria below.
  • Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children from screening through 90 days after the last dose of study drug and must refrain from donating sperm during this period. Permitted methods in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed.
  • Female participants of childbearing potential must have a negative pregnancy test at screening (serum) and before the first dose on Day 1 (urine). Female participants of childbearing potential must agree to take appropriate precautions to avoid pregnancy from screening through 190 days after the last dose of study drug and must refrain from donating oocytes during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed.
  • Women without childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible.
• Willing and able to undergo low-dose WBCT (excluding the head) imaging without requiring intubation.
• Willing and able to comply with study procedures and requirements and attend all study visits as defined in this Protocol.

Exclusion Criteria:

• Pregnant or breast-feeding.
• CAJIS score ≥ 24.
• FOP disease severity that in the investigator's opinion precludes participation (e.g., ankyloses of most or all joints, symptomatic thoracic insufficiency syndrome, or recurrent respiratory infections).
• History of uncontrolled or unstable cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening.
• Any clinically significant medical condition other than FOP that would, in the investigator's judgment, interfere with full participation in the study, pose a significant risk to the participant, or interfere with interpretation of study data.
• Presence of a clinically significant finding on echocardiogram (as assessed by the investigator).
• Presence of an abnormal finding on ECG at screening that in the investigator's opinion is clinically significant and/or the following ECG parameters: QTcF interval > 450 milliseconds, QRS interval > 120 milliseconds, PR interval > 220 milliseconds, ECG evidence of Brugada syndrome, atrial fibrillation or atrial flutter, or Mobitz II or higher grade atrioventricular block.
• Current treatment with a potent/strong inhibitor or inducer of CYP3A4 within 5 half-lives before the first dose of study treatment or expected to receive such treatment during the study.
  • Note: Topical ketoconazole is allowed.
• Use of the following medications:
  • Imatinib 30 days prior to baseline (Day 1 visit);
  • Any medication that might interfere with HO formation in the 90 days before baseline (Day 1 visit);
  • Bisphosphonates within 1 year of screening.
• Participation in an investigational drug study for the treatment of FOP or any other indication within 30 days or 5 half-lives (whichever is longer) before baseline (Day 1 visit).
• Planning to receive a live vaccine during the course of the study or within 6 weeks after the last dose of study drug.
• Known or suspected allergy to INCB000928 or any component of the study drug.
• Known history of clinically significant drug or alcohol abuse as defined by the investigator in the l year before baseline (Day 1 visit).
• Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
• HIV, HBV, or HCV infection.

Note: Successfully treated HCV is allowed.

• Participants with laboratory values at screening defined in Table 11.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/31/2024. Questions regarding updates should be directed to the study team contact.