INCB000928 for Stone Man Syndrome

(Progress Trial)

Recruiting at 74 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Incyte Corporation

Must not be taking: Antibiotics, Antifungals, Antivirals

Disqualifiers: Pregnancy, HIV, HBV, HCV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called INCB000928 (Zilurgisertib) for fibrodysplasia ossificans progressiva (FOP), a rare condition where muscles and tissues gradually turn into bone. The research aims to evaluate the treatment's effectiveness, safety, and tolerability compared to a placebo. Participants will be divided into age-based groups and will receive either the treatment or a placebo for 24 weeks, with an option to continue the treatment longer. Individuals with a clinical diagnosis of FOP who can undergo certain medical imaging without intubation may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a chronic or active infectious disease requiring treatment, you may be excluded from participating.

Is there any evidence suggesting that INCB000928 is likely to be safe for humans?

Research shows that INCB000928 is under investigation for its safety and effectiveness in treating fibrodysplasia ossificans progressiva (FOP), also known as Stone Man Syndrome. Earlier studies found that INCB000928 can target and block a protein responsible for FOP.

While detailed safety information from these studies isn't available, the progression of INCB000928 to a Phase 2 trial indicates it has passed initial safety checks in earlier research. This phase typically involves more participants to further assess safety and treatment tolerance. So far, no specific side effects have been widely reported, which is encouraging. However, it's important to remember that this research is ongoing, and new safety information could emerge as the study continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Stone Man Syndrome?

Unlike the standard treatments for Stone Man Syndrome (fibrodysplasia ossificans progressiva), which mainly involve managing symptoms with corticosteroids and pain relievers, INCB000928 is unique because it targets the root cause of the condition. This investigational drug works by inhibiting a specific pathway involved in abnormal bone formation, potentially preventing the disease from progressing rather than just alleviating symptoms. Researchers are excited about INCB000928 because it offers the possibility of not just slowing down the disease but also improving the quality of life for patients by addressing the underlying mechanisms of the condition.

What evidence suggests that INCB000928 might be an effective treatment for Stone Man Syndrome?

Research shows that INCB000928, which participants in this trial may receive, blocks the ACVR1 protein responsible for fibrodysplasia ossificans progressiva (FOP). This protein causes unusual bone growth in muscles and other tissues. Preclinical studies have shown that this drug can reduce the activity of the faulty protein, potentially slowing or stopping the extra bone growth seen in FOP. Although studies with people are ongoing, the mechanism of this drug offers hope that INCB000928 could effectively manage this condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Amanda McBride, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for adults and adolescents aged 12 or older with fibrodysplasia ossificans progressiva (FOP), also known as Stone Man Syndrome. Participants must be able to undergo specific imaging procedures without intubation and agree to prevent pregnancy or fathering children. Those with severe FOP, certain infections like HIV/HBV/HCV, a high CAJIS score, or other medical conditions that could affect the study can't join.

Inclusion Criteria

Further inclusion criteria apply

I am 12 or older and have been diagnosed with FOP.

You are willing to prevent pregnancy or becoming a parent based on the conditions described below.

Exclusion Criteria

Pregnant or breast-feeding

Note: Further exclusion criteria apply.

CAJIS score ≥ 24

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either INCB000928 or placebo for 24 weeks

24 weeks

Visits at Baseline, Week 12, and Week 24

Open-label Extension

Participants who complete the double-blind period receive INCB000928 for an additional 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• INCB000928
• Placebo

Trial Overview The trial is testing INCB000928's effectiveness, safety, and how well it's tolerated in people with FOP compared to a placebo. It's a Phase 2 study where participants are randomly assigned to either receive INCB000928 or a placebo without knowing which one they're getting (double-blind).

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 2 Interventions

Participants (2 to \< 6 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.

Group II: Cohort 2 Experimental Treatment 2 Interventions

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.

Group III: Cohort 1 Experimental Treatment 2 Interventions

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.

INCB000928 is already approved in United States for the following indications:

Approved in United States as Zilurgisertib for:

• Fibrodysplasia ossificans progressiva (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05090891

Study Details | NCT05090891 | To Assess the Efficacy, ... This Phase 2, Randomized, Double-Blind, Placebo-Controlled Study is intended to evaluate the Efficacy, Safety, and Tolerability and PK of INCB000928 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10378717/

Novel Therapeutic Targets for Fibrodysplasia Ossificans ... This narrative review provides an overview of the disease and explores emerging strategies for FOP treatment.

3. withpower.com withpower.com/trial/phase-3-myositis-ossificans-11-2021-46c73

INCB000928 for Stone Man Syndrome (Progress Trial) Trial Overview The trial is testing INCB000928's effectiveness, safety, and how well it's tolerated in people with FOP compared to a placebo. It's a Phase 2 ...

4. ifopa.org ifopa.org/incb000928_trial

PROGRESS Trial (zilurgisertib) Zilurgisertib (INCB000928) is an oral investigational drug designed to target and block this disease-causing mutant FOP protein hyperactivity. In preclinical ...

5. academic.oup.com academic.oup.com/jbmrplus/advance-article/doi/10.1093/jbmrpl/ziaf150/8258639?searchresult=1

Medical guidelines for fibrodysplasia ossificans progressiva Effective therapies for FOP will likely be based on the results of clinical trial interventions that modulate overactive ACVR1 signaling.

6. trials.arthritis.org trials.arthritis.org/trials/NCT05090891

To Assess the Efficacy, Safety, and Tolerability of INCB000928 ... This Phase 2, Randomized, Double-Blind, Placebo-Controlled Study is intended to evaluate the Efficacy, Safety, and Tolerability and PK of INCB000928 ...