To Assess the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva

NCT05090891 — Phase 2, Recruiting, 98 participants, Incyte Corporation

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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva

Registry	NCT05090891, acronym Progress
Status	Recruiting
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: double, treatment
Enrollment	98 (Estimated)
Sponsor	Incyte Corporation (Industry)
Conditions	Fibrodysplasia Ossificans Progressiva (FOP)
Interventions	INCB000928, Placebo (Drug)
Dates	start 2022-05-05, primary completion 2027-07-30 (estimated), completion 2033-01-20 (estimated), first posted 2021-10-25, last updated 2026-10-22
Locations	24 sites in United States, Argentina, Australia, Brazil, Canada, Chile, China, France and 9 more countries

-Summary

This Phase 2, Randomized, Double-Blind, Placebo-Controlled Study is intended to evaluate the Efficacy, Safety, and Tolerability and PK of INCB000928 administered to participants with a clinical diagnosis of fibrodysplasia ossificans progressiva (FOP).

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+Arms and interventions

Arm	Type	Interventions	Description
Cohort 1	Experimental	Drug: INCB000928; Drug: Placebo	Participants (≥ 12 years of age) will receive INCB000928 or placebo as defined in the protocol for 24 weeks (double-blind period). Participants who complete the double-blind period will continue into open-label extension period for an additional 292 weeks.
Cohort 2	Experimental	Drug: INCB000928; Drug: Placebo	Participants (6 to < 12 years of age) will receive INCB000928 or placebo as defined in the protocol for 24 weeks (double-blind period). Participants who complete the double-blind period will continue into open-label extension period for an additional 292 weeks.
Cohort 3	Experimental	Drug: INCB000928; Drug: Placebo	Participants (2 to < 12 years of age) will receive INCB000928 or placebo as defined in the protocol for 24 weeks (double-blind period). Participants who complete the double-blind period will continue into open-label extension period for an additional 292 weeks.

INCB000928 (Drug), also known as zilurgisertib: INCBG000928 will be administered QD orally.
Placebo (Drug): Placebo will be administered QD orally.

+Outcome measures

Primary outcomes

Double Blind Period: Occurrence of new heterotopic ossification (HO) lesions from baseline [Week 24]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) compared to baseline during the double-blind period.

Secondary outcomes

Double Blind Period: Number of new HO lesions from baseline [Week 24]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) compared to baseline during the double-blind period.
Double Blind Period: Total volume of new HO lesions from baseline [Week 24]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) compared to baseline during the double-blind period.
Double Blind Period: Change in the total volume of all HO lesions from baseline [Week 24]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) compared to baseline during the double-blind period.
Double Blind Period: Number of new flares from baseline [Week 24]: Based on Fibrodysplasia Ossificans Progressiva - Patient RepOrted syMPtoms Tool (FOP-PROMPT).
Number of Participants with Treatment Emergent Adverse Events (TEAE) [Up to 316 weeks]: Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Open-Label Extension: Occurrence of new HO lesions from Week 24 [Week 48]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
Open-Label Extension: Number of new HO lesions from Week 24 [Week 48]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
Open-Label Extension: Total volume of new HO lesions from Week 24 [Week 48]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
Open-Label Extension: Change in the total volume of all HO lesions from Week 24 [Week 48]: HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
Open-Label Extension: Number of new flares from Week 24 [Week 48]: Based on Fibrodysplasia Ossificans Progressiva - Patient RepOrted syMPtoms Tool (FOP-PROMPT) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
Pharmacokinetics Parameter: Cmax of INCB000928 [Baseline, Weeks 12, 24, 48 and 76]: Maximum observed concentration.
Pharmacokinetics Parameter: Tmax of INCB000928 [Baseline, Weeks 12, 24, 48 and 76]: Time to maximum concentration.
Pharmacokinetics Parameter: Cmin of INCB000928 [Baseline, Weeks 12, 24, 48 and 76]: Minimum observed concentration.
Pharmacokinetics Parameter: AUCt of INCB000928 [Baseline, Weeks 12, 24, 48 and 76]: Area under the plasma concentration-time curve from time 0 to the last quantifiable measurable plasma concentration

+Eligibility

Sex: All, ages: 2 Years to 99 Years

Inclusion Criteria:

* Female and male participants:

  * Cohort 1: ≥ 12 years of age.
  * Cohort 2: 6 to < 12 years of age.
  * Cohort 3: 2 to < 12 years of age (after eDMC review of safety data from Cohort 2).
* Clinical diagnosis of FOP.
* Willingness to avoid pregnancy or fathering children based on the criteria below.
* Willing and able to undergo low-dose WBCT (excluding the head) imaging without requiring intubation.
* Further inclusion criteria apply.

Exclusion Criteria:

* Pregnant or breast-feeding.
* CAJIS score ≥ 24.
* FOP disease severity that in the investigator's opinion precludes participation.
* 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.
* Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
* HIV, HBV, or HCV infection. Note:
* Further exclusion criteria apply.

+Locations (24)

Facility	City	Country	Status
Mayo Clinic Rochester	Rochester, Minnesota	United States	Recruiting
Children'S Hospital of Philadelphia	Philadelphia, Pennsylvania	United States	Recruiting
Penn Medicine - Perelman Center For Advanced Medicine	Philadelphia, Pennsylvania	United States	Active not recruiting
Hospital Italiano de Buenos Aires	Buenos Aires	Argentina	Active not recruiting
Royal North Shore Hospital	St Leonards, New South Wales	Australia	Completed
Murdoch Children'S Research Institute	Parkville, Victoria	Australia	Active not recruiting
Albert Einstein Israelite Hospital	São Paulo	Brazil	Active not recruiting
University Health Network Toronto General Hospital	Toronto, Ontario	Canada	Active not recruiting
Centro de Estudios Reumatologicos	Santiago	Chile	Active not recruiting
Beijing Childrens Hospital Capital Medical University	Beijing	China	Recruiting
Tongji Hospital of Tongji University	Shanghai	China	Recruiting
Shanghai Childrens Medical Center	Shanghai	China	Recruiting
Childrens Hospital of Fudan University	Shanghai	China	Recruiting
Ap-Hp Hopital Lariboisiere	Paris	France	Recruiting
Hopital Necker-Enfants Malades	Paris	France	Recruiting
Uniklinik Koln	Cologne	Germany	Recruiting
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore	Rome	Italy	Active not recruiting
Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra	Tlalpan	Mexico	Active not recruiting
Amsterdam Umc - Vu Medisch Centrum (Vumc)	Amsterdam	Netherlands	Recruiting
Starship Childrens Hospital	Auckland	New Zealand	Active not recruiting
Groote Schuur Hospital Radiation Oncology	Cape Town	South Africa	Active not recruiting
Seoul National University Hospital	Seoul	South Korea	Active not recruiting
Hospital Universitario Ramon Y Cajal	Madrid	Spain	Recruiting
Royal National Orthopaedic Hospital	Stanmore	United Kingdom	Active not recruiting

+Publications

Results publication: Yang YO, Fang Y, Wang P, Liu X, Getsy J, Rockich K. Effects of Renal and Hepatic Impairment on the Pharmacokinetics of Zilurgisertib. Br J Clin Pharmacol. 2026 May;92(5):1339-1351. doi: 10.1002/bcp.70372. Epub 2025 Dec 8. PMID 41360500

+Investigators

Amanda McBride, MD, Study director, Incyte Corporation

+Funding

NIH grants: 2023