What side effects are associated with this type of intervention?

Palovarotene, a RARγ agonist, is being studied for its safety and efficacy in treating Fibrodysplasia Ossificans Progressiva (FOP). Common side effects of treatments like palovarotene may include dry skin, mucocutaneous events, and potential teratogenic effects. As with any medication, it is essential to monitor for adverse reactions and consult with a healthcare provider to manage any side effects effectively.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Fibrodysplasia Ossificans Progressiva (FOP). Palovarotene, a RARγ agonist, is currently being studied for its safety and efficacy in treating FOP. This investigational drug aims to reduce abnormal bone growth associated with the condition. Other treatments for FOP are primarily supportive and symptomatic, focusing on managing pain and mobility issues.

What other types of research exist?

As of 2024, promising novel alternatives to Palovarotene for treating Fibrodysplasia Ossificans Progressiva (FOP) include: 1. Regeneron Pharmaceuticals' REGN2477 (Garetosmab), an anti-Activin A monoclonal antibody, which has shown potential in reducing new bone formation. 2. Clementia Pharmaceuticals' Saracatinib, a Src kinase inhibitor, which is being investigated for its ability to inhibit the signaling pathways involved in ectopic bone formation. 3. Gene therapy approaches targeting the ACVR1 gene mutation responsible for FOP, which are in early stages of research but hold significant promise for long-term treatment.

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Retinoic Acid Receptor Agonist

Palovarotene for Stone Man Syndrome (PIVOINE Trial)

Q: What is the mechanism of action of this treatment?

Stone Man Syndrome, or Fibrodysplasia Ossificans Progressiva (FOP), is a rare genetic disorder characterized by the abnormal development of bone in muscles, tendons, and other connective tissues. The most common treatments aim to inhibit the inappropriate bone formation. Palovarotene, a retinoic acid receptor gamma (RARγ) agonist, is one such treatment under investigation. It works by binding to RARγ, which regulates gene expression involved in bone growth and differentiation. By modulating these pathways, Palovarotene can potentially reduce the formation of heterotopic bone, thereby alleviating symptoms and improving quality of life for FOP patients. This mechanism is crucial as it directly targets the pathological process of bone formation, offering a more specific and potentially effective treatment option compared to broader anti-inflammatory or immunosuppressive therapies.

Phase 3

Waitlist Available

Research Sponsored by Ipsen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must be ≥14 years of age (aligned with the age of treated participants in the ongoing parent studies PVO-1A-301 and PVO-1A-202/PVO-1A-204) and qualify as 100% skeletally mature (if <18 years, based on assessments carried out at parent EOS Visit; if ≥18 years, automatically considered 100% skeletally mature) or have reached final adult height based on investigator's assessment, at the time the Study CLIN- 60120-452 informed consent is signed.

Must not have

Symptomatic vertebral fracture.

Use of concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up three years.

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing a medication called palovarotene to help people with a rare condition called Fibrodysplasia Ossificans Progressiva (FOP). FOP causes muscles and other soft tissues to turn into bone. Palovarotene aims to stop this abnormal bone growth by blocking certain signals in the body. The study includes both adults and children.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Palovarotene may cause side effects such as dry skin, eye problems like conjunctivitis, headaches, joint pain, hair loss, and possibly liver issues indicated by elevated enzyme levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a painful broken bone in my spine.

Select...

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

Select...

I am allergic to retinoids, gelatin, lactose, or palovarotene, or palovarotene didn't work for me.

Select...

I do not have any broken bones that are currently healing.

Select...

My amylase or lipase levels are more than twice the normal limit, or I have chronic pancreatitis.

Select...

I am not taking vitamin A, beta carotene, multivitamins, herbal preparations, or fish oil, or I am willing to stop during treatment.

Select...

My fasting triglycerides are over 400 mg/dL, even with treatment.

Select...

I do not have any uncontrolled major health issues.

Select...

I am not taking tetracycline or similar medications due to risk of a rare brain condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ three years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~three years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and three years. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence and description of all serious and non-serious treatment-emergent adverse events (TEAEs) whether or not they are considered as related to the study intervention;

Secondary study objectives

Raw values and change from the Inclusion Visit in % of worst score for total score, upper extremities subscore and mobility subscore

Raw values and change from the Inclusion Visit in physical and mental function (mean global physical and mental health score converted into T-scores)

Raw values and shift from the Inclusion Visit in the use of assistive devices and adaptations for daily living

Side effects data

From 2022 Phase 3 trial • 107 Patients • NCT03312634

50%

Dry skin

50%

Alopecia

50%

Pruritus

50%

Dry Eye

50%

Rash

25%

Paronychia

25%

Hypoacusis

25%

Condition Aggravated

25%

Anemia

25%

Erythema

25%

Skin exfoliation

25%

Skin irritation

25%

Chapped Lips

25%

Nasopharyngitis

25%

Musculoskeletal Pain

25%

Skin Abrasion

25%

Headache

25%

Skin Fissures

25%

Skin Disorder

25%

Skin Burning Sensation

25%

Hypotrichosis

25%

Swelling Face

25%

Musculoskeletal Stiffness

25%

Dizziness

25%

Hyperesthesia

25%

Oropharyngeal Pain

25%

Tinnitus

25%

Pain

25%

Visual Impairment

25%

Ocular Hyperemia

25%

Alanine Aminotransferase Increased

25%

Blood Alkaline Phosphatase Increased

25%

Nausea

25%

Breast Cyst

25%

Pruritus generalized

25%

Gamma-Glutamyltransferase Increased

100%

80%

60%

40%

20%

Study treatment Arm

Flare-Up Treatment: Supplemental SS

Untreated (PVO-1A-001)

Palovarotene 20/10 mg

Untreated (PVO-1A-001)

Palovarotene 5 mg

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Palovarotene Chronic/Flare-Up RegimenExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Palovarotene

2014

Completed Phase 3

~260

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Stone Man Syndrome, or Fibrodysplasia Ossificans Progressiva (FOP), is a rare genetic disorder characterized by the abnormal development of bone in muscles, tendons, and other connective tissues. The most common treatments aim to inhibit the inappropriate bone formation. Palovarotene, a retinoic acid receptor gamma (RARγ) agonist, is one such treatment under investigation. It works by binding to RARγ, which regulates gene expression involved in bone growth and differentiation. By modulating these pathways, Palovarotene can potentially reduce the formation of heterotopic bone, thereby alleviating symptoms and improving quality of life for FOP patients. This mechanism is crucial as it directly targets the pathological process of bone formation, offering a more specific and potentially effective treatment option compared to broader anti-inflammatory or immunosuppressive therapies.

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