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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Fibrodysplasia Ossificans Progressiva (FOP)
• Intervention / Treatment: Drug: INCB000928; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (US); Phone Number: 1.855.463.3463; Email: medinfo@incyte.com
• Study Contact Backup: Name: Incyte Corporation Call Center (ex-US); Phone Number: +800 00027423; Email: eumedinfo@incyte.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, CO 1181
    • Active, not recruiting
    • Hospital Italiano de Buenos Aires
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 02065
      • Completed
      • Royal North Shore Hospital
  • Victoria
    • Parkville, Victoria, Australia, 03052
      • Active, not recruiting
      • Murdoch Children's Research Institute
• Brazil
  • São Paulo, Brazil, 05652-900
    • Active, not recruiting
    • Albert Einstein Israelite Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Active, not recruiting
      • University Health Network Toronto General Hospital
• Chile
  • Santiago, Chile, 7501126
    • Active, not recruiting
    • Centro de Estudios Reumatologicos
• China
  • Beijing, China, 100045
    • Recruiting
    • Beijing Childrens Hospital Capital Medical University
  • Shanghai, China, 200065
    • Recruiting
    • Tongji Hospital of Tongji University
  • Shanghai, China, 200127
    • Recruiting
    • Shanghai Childrens Medical Center
  • Shanghai, China, 201102
    • Recruiting
    • Childrens Hospital of Fudan University
• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital Necker-Enfants Malades
  • Paris, France, 75010
    • Recruiting
    • Ap-Hp Hopital Lariboisiere
• Germany
  • Cologne, Germany, 50931
    • Recruiting
    • Uniklinik Koln
• Italy
  • Rome, Italy, 00168
    • Active, not recruiting
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
• Mexico
  • Tlalpan, Mexico, 14389
    • Active, not recruiting
    • Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • Amsterdam Umc - Vu Medisch Centrum (Vumc)
• New Zealand
  • Auckland, New Zealand, 01023
    • Active, not recruiting
    • Starship Childrens Hospital
• South Africa
  • Cape Town, South Africa, 07925
    • Active, not recruiting
    • Groote Schuur Hospital Radiation Oncology
• South Korea
  • Seoul, South Korea, 03080
    • Active, not recruiting
    • Seoul National University Hospital
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
• United Kingdom
  • Stanmore, United Kingdom, HA7 4LP
    • Active, not recruiting
    • Royal National Orthopaedic Hospital
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • Active, not recruiting
      • Penn Medicine - Perelman Center for Advanced Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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.	Drug: INCB000928; INCBG000928 will be administered QD orally.; Other Names: zilurgisertib; Drug: Placebo; Placebo will be administered QD orally.
Experimental: Cohort 2; 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.	Drug: INCB000928; INCBG000928 will be administered QD orally.; Other Names: zilurgisertib; Drug: Placebo; Placebo will be administered QD orally.
Experimental: Cohort 3; 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.	Drug: INCB000928; INCBG000928 will be administered QD orally.; Other Names: zilurgisertib; Drug: Placebo; Placebo will be administered QD orally.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Amanda McBride, MD, Incyte Corporation

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2022
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): January 20, 2033

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: fibrodysplasia ossificans progressiva (FOP); heterotopic ossification
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Pathologic Processes; Myositis; Pathological Conditions, Signs and Symptoms; Myositis Ossificans; Ossification, Heterotopic
• Other Study ID Numbers: INCB 00928-201; 2021-002286-17 (EudraCT Number); 2023-504129-38-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No