Inclusion Criteria (Part 1a, 1b, and 2):
1. Participant and/or guardian able and willing to give informed consent and/or assent as applicable, and willing to adhere to the visits schedule and study procedures.
2. Clinical diagnosis of FOP including congenital malformation(s) consistent with FOP (e.g., of the great toes), and either episodic soft tissue swelling consistent with an FOP flare-up and/or progressive HO.
4\. CAJIS score of ≤19. 5. Disease activity within 1 year of screening visit. Disease activity is defined as physician confirmed flare-up like symptoms or clinical progression including newly identified HO or worsening joint function.
6\. Able to understand, undergo, and perform all protocol related procedures, including low-dose WBCT-LH scan without sedation. Assistance from a caregiver is allowed.
7\. Agree to provide access to all relevant current and historical medical records (including radiographs or radiographic records) and growth records.
Inclusion Criteria (Part 1a only):
1. Male or female ≥ 15 years of age.
2. Serum creatinine ≤ upper limit of normal for age.
3. No open growth plates on bilateral PA hand/wrist or AP knee films at baseline
4. Able to receive IV radiotracer \[both IV access and no history of a reaction to radiotracer\].
5. No use of bisphosphonates or bone active agent within the past year.
6. At least 1 active HO lesion at baseline per Na18F PET/CT
Additional inclusion criteria apply including those listed above for all parts of the study.
Inclusion Criteria (Part 1b only):
1. Male or female ≥12 years of age.
2. History of multiple flare-up episodes within the past 6 months (to be reviewed and confirmed as qualifying by the PI together with the Sponsor). Qualifying flare-up episodes include any of the following:
* At least 3 qualifying flare-ups in the past 6 months each with continuous symptoms for at least 1 week
* Migratory flare-up swellings across the back
* Multiple flare-up episodes the sum of which lasted at least 21 days The timing of the individual flare-ups can be overlapping; they may be ongoing at the time of enrollment or resolved.
3. The qualifying flare-ups must involve at least 2 of the following flare-up symptoms:
* Pain
* Soft tissue swelling
* Warmth
* Redness
* Joint stiffness
* Decreased range of motion
Additional inclusion criteria apply including those listed above for all parts of the study.
Inclusion Criteria (Part 2 only):
1. Initial enrollment age requirement is ≥12 years
2. Enrollment may be extended to participants ≥6 years of age after safety in adult and participants age 12-17 years has been established.
3. Enrollment of participants ≥2 to \<6 years of age will commence after safety in adult and participants ≥6 years of age has been established.
Additional inclusion criteria apply including those listed above for all parts of the study.
Exclusion Criteria:
1. Body weight \<10kg
2. Known non-healed fracture at time of Study Day 1.
3. Planned surgery within the timeframe of the study duration or still recovering from recent surgery.
4. Respiratory compromise that requires use of supplemental oxygen.
5. Participant has
* Known monogenic disorder other than FOP.
* Bone or mineral disorder unrelated to FOP.
6. Malignancy (within the past 5 years, except non-melanoma skin cancer, cervical carcinoma in situ, or ductal carcinoma in situ \[DCIS\]).
7. Known active infection (including fungal, bacterial, mycobacterial, or viral infection including COVID19)
8. Uncontrolled hypoparathyroidism or hyperparathyroidism.
9. Per participant report or chart review (no testing required): Uncontrolled hyperthyroidism
10. Use of the following medication:
* Systemic corticosteroids with a prednisone equivalent of \>10mg/day within 1 week of Study Day 1. If the participant requires chronic use of \>10mg/day prednisone equivalent of corticosteroids, eligibility will be discussed with the Sponsor.
* NSAIDs of higher than doses recommended by the May 2022 ICCFOP guidelines within 1 week of Study Day 1. If the participant requires chronic use of NSAIDs at doses higher than those recommended by the May 2022 ICCFOP guidelines doses, eligibility will be discussed with the Sponsor.
* Current or chronic use of tetracycline drugs (e.g., tetracycline, demeclocycline, doxycycline, or minocycline).
11. Chronic use of any of unproven therapies for FOP.
12. Palovarotene
* Within 1 month of Study Day 1 for all participants
* Within 2 years of Study Day 1 for female participants \<8 years of age Or male participants \<10 years of age
13. Treatment with another investigational product within 5 half lives of last dose at the time of Study Day 1 or 1 month, whichever is longer.
14. History of allergy or hypersensitivity to andecaliximab or its excipients.
15. Significant current laboratory abnormalities
16. Breastfeeding, pregnant, or planning pregnancy.
17. Those of childbearing potential unwilling to agree to abstain from sexual activity that could result in pregnancy or unwillingness to use acceptable birth control during the study and for 90 days after the last dose.
18. Simultaneous participation in another clinical trial involving another investigational product.
19. Significant medical condition or disability or biochemical or hematologic abnormalities that in the opinion of the Investigator would expose the participant to undue risk, prevent the conduct of study procedures, or confound the study results.
Note: Other protocol defined Inclusion/Exclusion Criteria apply
