Palovarotene for Stone Man Syndrome

(PIVOINE Trial)

No longer recruiting at 12 trial locations

Overseen By Ipsen Recruitment Enquiries

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Ipsen

Must not be taking: Vitamin A, Tetracyclines, CYP450 inhibitors, others

Disqualifiers: Allergy to retinoids, Uncontrolled diseases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called palovarotene for individuals with Stone Man Syndrome, a rare condition where muscles and tissues turn into bone. The goal is to assess the safety and effectiveness of palovarotene in managing this condition in both adults and children. Participants will take the medication regularly and in higher doses during flare-ups. This trial may suit those who have completed a previous related study and live with Stone Man Syndrome. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications, like vitamin A, beta carotene, and some herbal supplements, as well as avoid certain drugs like tetracycline and strong CYP450 3A4 inhibitors. The trial protocol does not specify a general requirement to stop all current medications, but you should discuss your specific medications with the study team.

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

Research has shown that palovarotene has been studied for its safety in people with Stone Man Syndrome, also known as fibrodysplasia ossificans progressiva (FOP). One study aimed to gather real-world safety data on individuals treated with palovarotene, focusing on both children and adults with FOP.

Previous patients who took palovarotene generally tolerated the treatment well. Although some side effects were reported, they did not raise major safety concerns for most individuals. Ongoing research in different groups helps ensure the treatment remains safe.

Since the current trial is in a late phase, palovarotene has already undergone earlier testing stages, indicating it is likely safe for humans. Safety boards have closely monitored the drug, adding confidence to its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about palovarotene for Stone Man Syndrome because it targets the underlying process of abnormal bone formation, unlike traditional treatments that mainly focus on managing symptoms. Palovarotene is a retinoic acid receptor gamma (RARγ) agonist, which means it can potentially prevent the development of extra bone that characterizes this condition. This specific mechanism of action could offer a more direct approach to halting disease progression, providing hope for improved outcomes compared to current standards of care, such as physical therapy and pain management.

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

Research has shown that palovarotene, the investigational treatment in this trial, may help treat Stone Man Syndrome, also known as fibrodysplasia ossificans progressiva (FOP). In previous studies, the drug significantly reduced the growth of new bone, a key problem in FOP. About 80% of patients experienced little to no abnormal bone growth, compared to only 20% of those who took a placebo. This suggests that palovarotene could effectively slow or stop harmful bone growth in this condition. However, while this marks significant progress, some results have varied, and more research is needed to ensure its long-term safety and effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

This trial is for males and females aged 14 or older with Fibrodysplasia Ossificans Progressiva (FOP) who have finished previous related studies. Participants under 18 must be fully skeletally mature, while those over 18 are presumed so. They should not have any conditions that could risk their safety or affect the study.

Inclusion Criteria

Participant has completed the EOS or End of Treatment Visit of Study PVO-1A-301 or PVO-1A-202 (PVO-1A-202 Parts C and D correspond to Study PVO-1A-204 in France) and did not previously withdraw consent from any of the parent studies to be eligible for Study CLIN-60120-452.

I am 14 or older and my bones have fully grown.

Exclusion Criteria

Suicidal ideation (type 4 or 5) or any suicidal behaviour at the Inclusion Visit as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS).

I have a painful broken bone in my spine.

I am not taking drugs that strongly affect liver enzyme CYP450 3A4 or drugs like imatinib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chronic and flare-up treatment with palovarotene

3 years

Regular visits every six months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Palovarotene

Trial Overview The trial is testing the continued use of Palovarotene capsules to assess its long-term safety and effectiveness in treating FOP. It's designed for patients from prior parent studies who might benefit from ongoing treatment.

How Is the Trial Designed?

Group I: Palovarotene Chronic/Flare-Up Regimen Experimental Treatment 1 Intervention

Chronic treatment: participants will receive 5 mg palovarotene or the dose received during participation in the parent study at the time of transition to Study CLIN-60120-452 or prior to interrupting/stopping palovarotene treatment. Flare-up treatment: at the time of a flare-up (or substantial high-risk traumatic event likely to lead to a flare-up) participants will receive 20 mg palovarotene for 28 days, followed by 10 mg palovarotene for 56 days.

Who Is Running the Clinical Trial?

Ipsen

Lead Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9804935/

Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP) The proportion of patients with no or minimal HO (primary endpoint) was hypothesized to be 20% with placebo and 80% with successful palovarotene treatment, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06089616?term=AREA%5BConditionSearch%5D(Fibrodysplasia%20ossificans%20progressiva%20OR%20%22fop%22%20OR%20%22%20progressive%20myositis%20ossificans%22%20OR%20%22%20progressive%20ossifying%20myositis%22%20OR%20%22%20stone%20man%20syndrome%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=6

A Study to Document and to Further Describe Long-term ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

3. fda.gov fda.gov/media/169787/download

Palovarotene Sources of Data for Efficacy and Efficacy Results. As outlined in Section 5.1 (Clinical Studies Conducted for Palovarotene Treatments in ...

4. mednexus.org mednexus.org/doi/10.1002/rai2.12168

Future of fibrodysplasia ossificans progressiva management Palovarotene shows promise in treating fibrodysplasia ossificans progressiva, though results vary and its safety requires further large-scale ...

5. science.org science.org/content/article/treatments-emerge-rare-catastrophic-bone-growth-disease

Treatments emerge for rare 'catastrophic' bone growth ... As the first approved targeted treatment for FOP, palovarotene became a landmark. But it has several drawbacks besides its cost. It doesn't stop ...

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

Novel Therapeutic Targets for Fibrodysplasia Ossificans ... Numerous medications, including palovarotene and rapamycin, are currently undergoing clinical trials for the treatment of Stoneman syndrome.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06089616

NCT06089616 | A Study to Document and to Further ... The main aim of this registry study will be to collect and assess real-world safety data on children and adult participants with FOP treated with palovarotene.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/215559Orig1s000OtherR.pdf

215559Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov Conduct a prospective observational registry study with safety objectives of comparing palovarotene exposed and unexposed patients with ...

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

Medical guidelines for fibrodysplasia ossificans progressiva M.A.Z. was a member of the Clementia/Ipsen Data Safety Monitoring Board (DSMB) during the Palovarotene clinical trials and is currently on the ...