Palovarotene for Myositis Ossificans

Phase-Based Progress Estimates
2
Effectiveness
3
Safety
Royal National Orthopaedic Hospital, London, United Kingdom
Myositis Ossificans+1 More
Palovarotene - Drug
Eligibility
Any Age
All Sexes
Eligible conditions
Select

Study Summary

A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.

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Eligible Conditions

  • Myositis Ossificans
  • Fibrodysplasia Ossificans Progressiva (FOP)

Treatment Effectiveness

Effectiveness Progress

2 of 3
This is further along than 85% of similar trials

Other trials for Myositis Ossificans

Study Objectives

This trial is evaluating whether Palovarotene will improve 1 primary outcome and 12 secondary outcomes in patients with Myositis Ossificans. Measurement will happen over the course of Every six months up to three years.

Every six months up to three years
Percentage of participants with new bone growth overall and by flare-up status
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 CAJIS (Cumulative Analogue Joint Involvement Scale) total score
Raw values and change from the Inclusion Visit in absolute and % predicted FEV1/FVC ratio
Raw values and change from the Inclusion Visit in number of investigator-reported flareups, flare-up outcomes (new bone growth, restricted movement) and flare-up duration by body location and overall;
Raw values and change from the Inclusion Visit in observed and % predicted DLCO (Diffusion Capacity of the Lung for Carbon Monoxide)
Raw values and change from the Inclusion Visit in observed and % predicted FEV1 (Forced Expiratory Volume in One Second)
Raw values and change from the Inclusion Visit in observed and % predicted FVC (Forced Vital Capacity)
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
Three years
Frequency of healthcare services utilization
Type and frequency of healthcare utilization
Three years.
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;

Trial Safety

Safety Progress

3 of 3
This is further along than 85% of similar trials

Other trials for Myositis Ossificans

Side Effects for

Palovarotene 10/5 mg
Dry skin
81%
Condition aggravated
62%
Arthralgia
48%
Headache
38%
Lip dry
33%
Nausea
29%
Chapped lips
24%
Diarrhoea
19%
Pruritus
19%
Pruritus generalised
19%
Dermatitis acneiform
19%
Dry mouth
14%
Erythema
14%
Lipase increased
10%
Irritability
10%
Excoriation
10%
Insomnia
10%
Post-traumatic pain
10%
Rash maculo-papular
10%
Skin exfoliation
10%
Pollakiuria
10%
Joint stiffness
10%
Eczema
10%
Joint swelling
10%
Musculoskeletal stiffness
10%
Pain in extremity
10%
Influenza
10%
Nasal congestion
5%
Cough
5%
Blood alkaline phosphatase increased
5%
Blood bilirubin increased
5%
Myoclonus
5%
Pyrexia
5%
Haemoglobin decreased
5%
Contusion
5%
Dizziness
5%
Dry eye
5%
Abdominal pain
5%
Migraine
5%
Vomiting
5%
Neck pain
5%
Upper respiratory tract infection
5%
Hypercholesterolaemia
5%
Muscle spasms
5%
Back pain
5%
Increased appetite
5%
Pharyngitis
5%
Blood thyroid stimulating hormone decreased
0%
Leukocytosis
0%
Amylase increased
0%
Fatigue
0%
Pallor
0%
Chest pain
0%
Haemorrhagic ovarian cyst
0%
Asthmatic crisis
0%
Feeling cold
0%
Blood potassium increased
0%
Application site erythema
0%
Vessel puncture site bruise
0%
Thrombocytopenia
0%
Fall
0%
Gamma-glutamyltransferase increased
0%
Thyroxine free increased
0%
Iron deficiency anaemia
0%
Eye pruritus
0%
Thyroxine increased
0%
Haematuria
0%
Rhinorrhoea
0%
Epistaxis
0%
Abdominal pain upper
0%
Skin hypopigmentation
0%
Vision blurred
0%
Flatulence
0%
Polyuria
0%
Hypoaesthesia
0%
Frequent bowel movements
0%
Glycosuria
0%
Pain of skin
0%
Ecchymosis
0%
Constipation
0%
Rash
0%
Dandruff
0%
Hyperglycaemia
0%
Dermatitis contact
0%
Macule
0%
Bone pain
0%
Myalgia
0%
Groin pain
0%
Nasopharyngitis
0%
Oral candidiasis
0%
Urinary tract infection
0%
This histogram enumerates side effects from a completed 2016 Phase 2 trial (NCT02190747) in the Palovarotene 10/5 mg ARM group. Side effects include: Dry skin with 81%, Condition aggravated with 62%, Arthralgia with 48%, Headache with 38%, Lip dry with 33%.

Trial Design

1 Treatment Group

Palovarotene Chronic/Flare-Up Regimen
1 of 1
Experimental Treatment

This trial requires 87 total participants across 1 different treatment group

This trial involves a single treatment. Palovarotene is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.

Palovarotene Chronic/Flare-Up Regimen
Drug
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
Not yet FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: three years.
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly three years. for reporting.

Closest Location

University of California San Francisco (UCSF) - San Francisco, CA

Eligibility Criteria

This trial is for patients born any sex of any age. There are 2 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
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.
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.

Patient Q&A Section

What is myositis ossificans?

"Myositis ossificans must be differentiated from Myophtosis and should be treated by an orthopaedic surgeon. Myositis ossificans occurs in an adult following trauma to the arm and presents as an ossified lump in the muscles. There are different forms of Myositis Ossificans. In myositis ossificans progress of the tumour can be seen. All orthopaedic surgeons must be aware of this process and have experience of it as early diagnosis is essential." - Anonymous Online Contributor

Unverified Answer

What are the signs of myositis ossificans?

"MOS involves the upper limb. It may develop quickly in cases with recent fractures in the proximal humerus. The condition is characterised by pain, swelling and weakness. There is normally remodelling in the affected area as the condition resolves but the presence of inflammation is typically indicated by raised levels of the enzyme CK. If this is not the case then a skeletal biopsy to look for muscle fibrosis and infiltrate is required to make the diagnosis. When myositis ossificans develops in the upper limb this should raise the possibility of metastasis. There may be an underlying condition such as metastatic breast tumour but this is not always the case." - Anonymous Online Contributor

Unverified Answer

Can myositis ossificans be cured?

"Myositis ossificans cannot be cured. In this subacute disorder, treatment should be directed at reducing inflammation and accelerating healing. Early initiation of antirheumatic drugs in addition to physical therapy and occupational therapy may help." - Anonymous Online Contributor

Unverified Answer

What are common treatments for myositis ossificans?

"No effective treatments have been found for MOS, except some treatments for soft tissue tumors. Most treatments are surgical, and therefore the results are unclear at present. The use of steroids or radiotherapy, which have been investigated in this situation, is currently considered to be risky. There is a need for a large-scale, randomized, and controlled trial of treatment for patients with MOS." - Anonymous Online Contributor

Unverified Answer

How many people get myositis ossificans a year in the United States?

"About 18,000 people are diagnosed with MO in a year the United States. However, the true numbers are likely much higher. MO is more common in males and in black and white patients." - Anonymous Online Contributor

Unverified Answer

What causes myositis ossificans?

"This case highlights the challenge we face in diagnosing skeletal myositis ossificans, and has implications for the use of current diagnostic criteria when assessing individuals with chronic inflammatory myopathies such as polymyositis and dermatomyositis." - Anonymous Online Contributor

Unverified Answer

Does palovarotene improve quality of life for those with myositis ossificans?

"Palovarotene significantly improved quality of life and muscular strength of both hands and legs for patients with MIO. The findings of this pilot study validate the use of palovarotene for treatment of skeletal pain in MIO." - Anonymous Online Contributor

Unverified Answer

Have there been other clinical trials involving palovarotene?

"Only one previous study evaluated the effects of a Palovarotene analogue: "Palovar" (Eligard, C.R. Pharmaceuticals, Inc.) as monotherapy in patients with metastatic [colorectal cancer](https://www.withpower.com/clinical-trials/colorectal-cancer). Based on this single-arm multicenter, sequential trial, Palovar did not demonstrate any antitumor impact. summary: Results from a recent paper is evaluating whether a substance that resembles vitamin A may help in two different cancers." - Anonymous Online Contributor

Unverified Answer

What are the latest developments in palovarotene for therapeutic use?

"A new formulation of 1.2 mg palovarotene is well tolerated, is absorbed well, and is much more convenient for use as a therapy for myositis ossificans. Palovarotene appears to produce better clinical results when administered at 2 mg twice a day rather than at 1.2 mg daily." - Anonymous Online Contributor

Unverified Answer

Who should consider clinical trials for myositis ossificans?

"Patients with MIO have a poor prognosis and must therefore be treated cautiously in observational cohorts and RCTs. Patients with limited evidence regarding treatment and limited evidence of disease in the upper extremities may receive greater benefit with clinical trial-based care." - Anonymous Online Contributor

Unverified Answer

How does palovarotene work?

"Palovarotene induces apoptosis in myoblast cells through p53 upregulation. This observation provides an insight into an alternative mode of action by which palovarotene could be therapeutically beneficial in the treatment of muscular dystrophy." - Anonymous Online Contributor

Unverified Answer

Has palovarotene proven to be more effective than a placebo?

"In patients with early-stage myositis ossificans, palovarotene produced a shorter time to pain resolution and was as effective as a placebo. The risk of discontinuation, however, in both the palovarotene and placebo arms was the same." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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