A Phase 3 interventional study of Palovarotene in Fibrodysplasia Ossificans Progressiva, sponsored by Clementia Pharmaceuticals Inc.. Completed at 16 sites in 11 countries. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2023-11-29.
Sponsored by Clementia Pharmaceuticals Inc. (part of Ipsen) · Phase 3, Interventional, and Treatment
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO) often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to ankyloses of major joints with cumulative and irreversible loss of movement and disability.
One of the primary objectives was to evaluate the efficacy of palovarotene in decreasing new HO in participants with FOP as assessed by low-dose, whole body computed tomography (WBCT), excluding head, compared to untreated participants from Clementia's FOP natural history study (Study PVO-1A-001, NHS). The other primary objective was to evaluate the safety of palovarotene in participants with FOP.
This study was conducted in three parts. Part A was the main part of the study, Part B, the 2-year (24-month) extension and Part C was an up-to-2-year post last dose of study treatment follow-up for skeletally immature participants.
Participants in Part A and B received a chronic/flare-up dosing regimen of palovarotene for up to 4 years (48 months) as follows:
Note that all dosing was weight-adjusted in skeletally immature participants (those under the age of 18 years with less than 90% skeletal maturity on hand/wrist x-rays performed at Screening).
In part C, participants who were enrolled in Parts A or B who discontinued the study and were skeletally immature were invited back to participate in the off-treatment safety follow-up. No new participants were enrolled into Part C.
24 studies on the registry are indexed under Myositis Ossificans; 5 are open to participants now.
This study's enrollment of 107 is above the median of 48 across 16 interventional studies indexed under Myositis Ossificans.
Browse Myositis Ossificans studies →Clementia Pharmaceuticals Inc. is the lead sponsor of 10 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 3 (50%) have results posted.
First submitted before Clementia Pharmaceuticals Inc. became part of Ipsen.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received 5 mg palovarotene once daily for up to 48 months; and 20 mg palovarotene once daily for 28 days, followed by 10 mg for 56 days for flareups. (Dosing was adjusted for weight in skeletally immature subjects.)
Drug: Palovarotene
Palovarotene was taken orally once daily at approximately the same time each day following a meal.
Annualized New Heterotopic Ossification (HO)
The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.
Time frame: Baseline (within one month of screening/Day 1) and up to 24 months
Percentage of Participants With Any New HO
The new HO was assessed by WBCT scan. The percentage of participants with any new HO (volume \> 0 mm\^3) were analyzed using the Bayesian distribution. Results are presented for overall ITT period.
Time frame: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)
Number of Body Regions With New HO
All participants were analyzed for number of body regions with any new HO (new HO \> 0 mm\^3). The presence of HO across various body regions was analyzed using WBCT scan. Results are presented for overall ITT period
Time frame: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)
Percentage of Participants With Flare-Ups
Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary.
Time frame: Month 12
Ratio of Flare-Up Per Participant-Month of Exposure
Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary. The flare-up rate per participant-month exposure was analyzed using a negative binomial regression. Results are presented for overall ITT period.
Time frame: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)
This Phase 3, open-label study conducted in adult and pediatric participants with fibrodysplasia ossificans progressiva (FOP) at 16 centers in 11 countries (Argentina, Australia, Brazil, Canada, France, Italy, Japan, Spain, Sweden, the United Kingdom, and the US) between 30 November 2017 and 07 September 2022.
| Milestone | Palovarotene | Untreated (PVO-1A-001) |
|---|---|---|
| Started | 107 | 114 |
| Completed | 49 | 33 |
| Not completed | 58 | 81 |
| Withdrew: Adverse event | 11 | 0 |
| Withdrew: Sponsor request | 2 | 0 |
| Withdrew: Withdrawal by subject | 31 | 9 |
| Withdrew: Enrolled in an interventional study | 0 | 52 |
| Withdrew: Enrolled in an interventional study at time of a flare-up | 0 | 9 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Non-compliance | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Enrolled into non-interventional study | 0 | 5 |
| Withdrew: Worsening clinical condition | 0 | 1 |
| Withdrew: Participant did not want to travel | 0 | 1 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Other | 13 | 0 |
The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.
| cubic millimeters (mm^3) | Palovarotene | Untreated (PVO-1A-001) |
|---|---|---|
| Annualized New Heterotopic Ossification (HO) | 9427.1 ± 3084.0 | 23720.2 ± 4850.0 |
The new HO was assessed by WBCT scan. The percentage of participants with any new HO (volume \> 0 mm\^3) were analyzed using the Bayesian distribution. Results are presented for overall ITT period.
| percentage of participants | Palovarotene |
|---|---|
| Percentage of Participants With Any New HO | 83.5 |
All participants were analyzed for number of body regions with any new HO (new HO \> 0 mm\^3). The presence of HO across various body regions was analyzed using WBCT scan. Results are presented for overall ITT period
| body regions | Palovarotene |
|---|---|
| Number of Body Regions With New HO | 3.0 ± 1.68 |
Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary.
| percentage of participants | Palovarotene |
|---|---|
| Percentage of Participants With Flare-Ups | 64.6 |
Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary. The flare-up rate per participant-month exposure was analyzed using a negative binomial regression. Results are presented for overall ITT period.
| ratio of flare-up | Palovarotene |
|---|---|
| Ratio of Flare-Up Per Participant-Month of Exposure | 0.2 ± 0.40 |
Collected over Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Palovarotene 5 mg | 0/107 (0%) | 34/107 (31.8%) | 105/107 (98.1%) |
| Palovarotene 20/10 mg | 0/81 (0%) | 19/81 (23.5%) | 77/81 (95.1%) |
| Untreated (PVO-1A-001) | 1/114 (0.9%) | 0/114 (0%) | 0/114 (0%) |
| Event | Palovarotene 5 mg | Palovarotene 20/10 mg | Untreated (PVO-1A-001) |
|---|---|---|---|
| Epiphyses Premature FusionMusculoskeletal and connective tissue disorders | 11/107 | 10/81 | 0/114 |
| Corona virus infectionInfections and infestations | 10/107 | 2/81 | 0/114 |
| Condition AggravatedGeneral disorders | 2/107 | 3/81 | 0/114 |
| Exposure to communicable diseaseInjury, poisoning and procedural complications | 3/107 | 0/81 | 0/114 |
| Back PainMusculoskeletal and connective tissue disorders | 0/107 | 1/81 | 0/114 |
| Mobility DecreasedMusculoskeletal and connective tissue disorders | 0/107 | 1/81 | 0/114 |
| CellulitisInfections and infestations | 0/107 | 1/81 | 0/114 |
| Escherichia SepsisInfections and infestations | 0/107 | 1/81 | 0/114 |
| Mycoplasma InfectionInfections and infestations | 0/107 | 1/81 | 0/114 |
| PneumoniaInfections and infestations | 1/107 | 1/81 | 0/114 |
| Event | Palovarotene 5 mg | Palovarotene 20/10 mg | Untreated (PVO-1A-001) |
|---|---|---|---|
| Dry skinSkin and subcutaneous tissue disorders | 60/107 | 37/81 | 0/114 |
| Lip DryGastrointestinal disorders | 37/107 | 17/81 | 0/114 |
| Drug eruptionSkin and subcutaneous tissue disorders | 15/107 | 26/81 | 0/114 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 32/107 | 15/81 | 0/114 |
| AlopeciaSkin and subcutaneous tissue disorders | 19/107 | 21/81 | 0/114 |
| RashSkin and subcutaneous tissue disorders | 25/107 | 11/81 | 0/114 |
| Upper Respiratory Tract InfectionInfections and infestations | 23/107 | 6/81 | 0/114 |
| ErythemaSkin and subcutaneous tissue disorders | 11/107 | 16/81 | 0/114 |
| Pain In ExtremityMusculoskeletal and connective tissue disorders | 21/107 | 9/81 | 0/114 |
| PruritusSkin and subcutaneous tissue disorders | 19/107 | 14/81 | 0/114 |
The Principal Safety Set (Principal SS) included all enrolled participants in the Principal Enrolled Population (Principal EP) set \[ie, participants with the R206H activin receptor type IA (ACVR1) mutation\] receiving at least 1 dose of palovarotene in study PVO-1A-301. The Full Analysis Set (FAS) included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001 (NCT02322255).
| Age, Categorical(Participants) | Palovarotene | Untreated (PVO-1A-001) | Total |
|---|---|---|---|
| <=18 years | 75 | 70 | 145 |
| Between 18 and 65 years | 24 | 44 | 68 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Palovarotene | Untreated (PVO-1A-001) | Total |
|---|---|---|---|
| Female | 46 | 52 | 98 |
| Male | 53 | 62 | 115 |
| Ethnicity (NIH/OMB)(Participants) | Palovarotene | Untreated (PVO-1A-001) | Total |
|---|---|---|---|
| Hispanic or Latino | 19 | 23 | 42 |
| Not Hispanic or Latino | 69 | 73 | 142 |
| Unknown or Not Reported | 11 | 18 | 29 |
| Race/Ethnicity, Customized(Participants) | Palovarotene | Untreated (PVO-1A-001) | Total |
|---|---|---|---|
| White | 70 | 84 | 154 |
| Black or African American | 1 | 0 | 1 |
| Asian | 9 | 8 | 17 |
| American Indian or Alaska Native | 0 | 1 | 1 |
| Native Hawaiian or other Pacific Islander | 1 | 0 | 1 |
| Multiple | 6 | 2 | 8 |
| Other | 1 | 4 | 5 |
| Unknown | 11 | 15 | 26 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Undecided
Ran from Nov 2017 to primary completion in Jan 2020, 25 months.
Results were first posted in Mar 2023, 3 years 1 month after primary completion. A results delay was requested in Jan 2021.
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Studies of the drug tested here: Palovarotene
Clementia Pharmaceuticals Inc. →