Trial Outcomes & Findings for 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. (NCT NCT05027802)
NCT ID: NCT05027802
Last Updated: 2025-06-22
Results Overview
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or significant medical event. A TEAE was defined as any AE that occurred after signing the informed consent form of this study or an ongoing AE from the parent study with a worsening in severity or relationship to the study treatment following transition to this study.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
61 participants
Primary outcome timeframe
From signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
Results posted on
2025-06-22
Participant Flow
This single-arm, rollover, multicenter, Phase III, open-label study was conducted at 12 investigational sites in 9 countries from 14-Mar-2022 to 30-Nov-2024 in participants \>=14 years with fibrodysplasia ossificans progressiva (FOP) who had completed parent study PVO-1A-301 (NCT03312634) or PVO-1A-202 (NCT02279095)/PVO-1A-204 (NCT02979769) and continued to benefit from palovarotene therapy. A total of 61 participants were enrolled in the study of which 59 received treatment.
This study consisted of an Inclusion visit which included signing of informed consent form (Day 1), a continuous dosing treatment period (including a follow-up visit every 6 months), and an end of study/early withdrawal visit. Participants were eligible for the study whether they received chronic or flare-up treatment in the parent study at the time of transition.
Participant milestones
| Measure |
Palovarotene
Participants continued to receive palovarotene 5 milligram (mg) orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Overall Study
STARTED
|
61
|
|
Overall Study
Received Treatment
|
59
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
23
|
Reasons for withdrawal
| Measure |
Palovarotene
Participants continued to receive palovarotene 5 milligram (mg) orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Withdrawal by Subject
|
18
|
|
Overall Study
Death
|
2
|
|
Overall Study
Other
|
1
|
Baseline Characteristics
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.
Baseline characteristics by cohort
| Measure |
Palovarotene
n=59 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
16 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
White
|
38 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
2 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
15 Participants
n=93 Participants
|
|
Age, Continuous
|
22.4 years
STANDARD_DEVIATION 8.9 • n=93 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: From signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 monthsPopulation: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or significant medical event. A TEAE was defined as any AE that occurred after signing the informed consent form of this study or an ongoing AE from the parent study with a worsening in severity or relationship to the study treatment following transition to this study.
Outcome measures
| Measure |
Palovarotene
n=59 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
Serious TEAEs
|
9 Participants
|
|
Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
All TEAEs
|
54 Participants
|
|
Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
Non-serious TEAEs
|
53 Participants
|
|
Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
Serious treatment-related TEAEs
|
1 Participants
|
|
Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
Non-serious treatment-related TEAEs
|
38 Participants
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
The CAJIS is an objective measure of joint movement completed by the investigator to document total joint involvement. This scale assesses functional disability by categorizing range of motion across 12 joints (both right and left shoulder, elbow, wrist, hip, knee and ankle joints) and 3 body regions (cervical spine, thoracic/lumbar spine and jaw), with each joint/region assessed as: 0=normal (\<10% deficit); 1=partially impaired (10% to 90% deficit) and 2=functionally ankylosed (\>90% deficit). The CAJIS total score is calculated as the sum of the scores of all joints/regions and ranges from 0 (no involvement) to 30 (maximally involved). Higher score indicated worse outcome. The Inclusion Visit was the first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=53 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30
Month 12
|
1.1 score on a scale
Standard Deviation 2.0
|
|
Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30
Month 6
|
0.6 score on a scale
Standard Deviation 1.3
|
|
Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30
Month 18
|
1.5 score on a scale
Standard Deviation 2.3
|
|
Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30
Month 24
|
1.5 score on a scale
Standard Deviation 2.6
|
|
Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30
Month 30
|
2.0 score on a scale
Standard Deviation 4.7
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
The use of assistive devices and adaptations (aids) for daily living was collected using the FOP assistive devices assessment at each visit. Assistive devices and adaptations include mobility aids, eating tools, personal care tools, bathroom aids and devices, bedroom aids and devices, home adaptions, work environment adaptions, technology adaptions, sports and recreation adaptions, school adaptions and medical therapies for daily living. The mean of total number of assistive devices and adaptations for daily living being used is presented. The Inclusion Visit was the first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=53 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30
Month 18
|
1.4 number of aids
Standard Deviation 5.7
|
|
Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30
Month 24
|
1.2 number of aids
Standard Deviation 5.1
|
|
Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30
Month 6
|
-0.7 number of aids
Standard Deviation 3.4
|
|
Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30
Month 12
|
1.1 number of aids
Standard Deviation 4.7
|
|
Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30
Month 30
|
2.8 number of aids
Standard Deviation 7.4
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
The FOP-PFQ is a disease-specific patient-reported outcome measure of physical impairment; includes 28 questions related to activities of daily living and physical performance scored on a scale of 1 to 5 with lower scores indicating that participant has more difficulty completing those tasks. Total score, upper extremities subscore and mobility subscore is calculated as follows: total score: sum of the scores from each question (range 28 to 140); upper extremities subscore: sum of the scores from 15 questions (questions 1-12, 14, 25 and 26; range 15 to 75); mobility subscore: the sum of the scores from 13 questions (questions 13, 15-24, 27 and 28; range 13 to 65). The scores were transformed to reflect a percentage of worst score which ranged from 0% to 100% with 0% indicating the best possible function and 100% (higher score) indicating the worst possible function. Mean is presented. Inclusion Visit was first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=54 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 24: upper extremities subscore
|
5.54 percentage of score
Standard Deviation 12.42
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 30: upper extremities subscore
|
8.15 percentage of score
Standard Deviation 11.50
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 12: mobility subscore
|
3.90 percentage of score
Standard Deviation 14.98
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 6: total score
|
0.74 percentage of score
Standard Deviation 6.37
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 12: total score
|
2.39 percentage of score
Standard Deviation 10.21
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 18: total score
|
4.77 percentage of score
Standard Deviation 12.39
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 24: total score
|
7.80 percentage of score
Standard Deviation 15.15
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 30: total score
|
13.79 percentage of score
Standard Deviation 21.98
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 6: upper extremities subscore
|
0.70 percentage of score
Standard Deviation 6.87
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 12: upper extremities subscore
|
1.12 percentage of score
Standard Deviation 8.52
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 18: upper extremities subscore
|
3.24 percentage of score
Standard Deviation 11.28
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 6: mobility subscore
|
0.74 percentage of score
Standard Deviation 9.15
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 18: mobility subscore
|
6.53 percentage of score
Standard Deviation 17.45
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 24: mobility subscore
|
10.38 percentage of score
Standard Deviation 23.08
|
|
Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30
Month 30: mobility subscore
|
20.30 percentage of score
Standard Deviation 36.44
|
SECONDARY outcome
Timeframe: Up to approximately 32 monthsPopulation: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
Annualized HU rate was defined as the (number of HU during the study/duration of participant participation in the study in days) \* 365.25. Annualized rate for total health care services utilized is presented.
Outcome measures
| Measure |
Palovarotene
n=55 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Annualized Rate of Healthcare Utilization (HU) in Participants With Fibrodysplasia Ossificans Progressiva
|
21.7 HU per participant year
Standard Deviation 31.4
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
Lung function parameters including FVC were obtained by spirometry. The Inclusion Visit was the first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=38 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30
Month 6
|
1.2 percent predicted FVC
Standard Deviation 5.5
|
|
Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30
Month 12
|
-0.7 percent predicted FVC
Standard Deviation 6.8
|
|
Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30
Month 18
|
-3.9 percent predicted FVC
Standard Deviation 9.8
|
|
Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30
Month 24
|
-1.6 percent predicted FVC
Standard Deviation 5.8
|
|
Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30
Month 30
|
-2.8 percent predicted FVC
Standard Deviation 3.8
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
Lung function parameters including FEV1 were obtained by spirometry. The Inclusion Visit was the first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=38 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30
Month 6
|
1.8 percent predicted FEV1
Standard Deviation 5.9
|
|
Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30
Month 12
|
-3.1 percent predicted FEV1
Standard Deviation 9.6
|
|
Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30
Month 18
|
-5.3 percent predicted FEV1
Standard Deviation 11.8
|
|
Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30
Month 24
|
-3.8 percent predicted FEV1
Standard Deviation 6.6
|
|
Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30
Month 30
|
-10.0 percent predicted FEV1
Standard Deviation 11.1
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
The ratio of FEV1 to FVC was calculated. Lung function parameters were obtained by spirometry. The Inclusion Visit was the first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=38 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30
Month 30
|
-0.1268 ratio
Standard Deviation 0.1564
|
|
Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30
Month 6
|
0.0163 ratio
Standard Deviation 0.0574
|
|
Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30
Month 12
|
-0.0323 ratio
Standard Deviation 0.1358
|
|
Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30
Month 18
|
-0.0137 ratio
Standard Deviation 0.0888
|
|
Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30
Month 24
|
-0.0365 ratio
Standard Deviation 0.0994
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
The DLCO test provides information on the efficiency of gas transfer from alveolar air into the bloodstream. The Inclusion Visit was the first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=36 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30
Month 6
|
-1.5 percent predicted DLCO
Standard Deviation 7.9
|
|
Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30
Month 12
|
-5.3 percent predicted DLCO
Standard Deviation 12.6
|
|
Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30
Month 18
|
-4.4 percent predicted DLCO
Standard Deviation 16.5
|
|
Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30
Month 24
|
-4.8 percent predicted DLCO
Standard Deviation 11.4
|
|
Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30
Month 30
|
-20.0 percent predicted DLCO
Standard Deviation 20.3
|
SECONDARY outcome
Timeframe: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
The PROMIS Global Health Scale is a patient-reported outcome measure of physical and mental function. The adult form (developed for participants \>=15 years old) was used for all participants,consists of 10 questions from which 2 scores are calculated: global physical health score (GPH) and global mental health (GMH) score, each ranging from 4 (worse health) to 20 (better health). GPH score:sum of scores from Questions 3, 6, 7 and 8 and GMH score:sum of scores from Questions 2, 4, 5 and 10.These scores were converted to a T-score whose distributions were standardized such that value of 50 represented average (mean) for general population and increments of +/- 10 points represented +/- 1 standard deviation away from the norm.Higher T-scores indicated better physical/mental health. A T-score \<50 indicated worse health than general population, while a T-score \>50 indicated better health. Inclusion Visit was first study visit (Day 1) and first administration of palovarotene in this study.
Outcome measures
| Measure |
Palovarotene
n=54 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 6: GPH
|
-0.6 T-score
Standard Deviation 4.4
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 12: GPH
|
-1.7 T-score
Standard Deviation 5.0
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 18: GPH
|
-2.9 T-score
Standard Deviation 5.0
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 24: GPH
|
-1.9 T-score
Standard Deviation 5.8
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 30: GPH
|
-3.9 T-score
Standard Deviation 7.0
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 6: GMH
|
-1.0 T-score
Standard Deviation 4.8
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 12: GMH
|
-1.5 T-score
Standard Deviation 6.3
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 18: GMH
|
-2.3 T-score
Standard Deviation 6.9
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 24: GMH
|
-2.2 T-score
Standard Deviation 6.0
|
|
Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
Month 30: GMH
|
-5.7 T-score
Standard Deviation 5.1
|
SECONDARY outcome
Timeframe: Months 6, 12, 18 and 24Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
Number of participants with at least 1 flare-up and intercurrent flare-ups since last visit is presented. Intercurrent flare-ups were defined as a new flare-up or marked worsening of the original flare up at any time during a flare-up-based treatment cycle. Outcome of flare-ups resulting in movement restriction and bone formations in participants is presented. Movement restriction includes categories like better, same, slightly worse, moderately worse and severely worse movement than before.
Outcome measures
| Measure |
Palovarotene
n=59 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: better movement
|
0 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: same movement
|
22 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: moderately worse movement
|
5 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: at least 1 flare up since last visit
|
27 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: at least 1 flare up since last visit
|
26 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: at least 1 flare up since last visit
|
15 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: at least 1 flare up since last visit
|
4 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: intercurrent flare-ups since last visit
|
7 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: intercurrent flare-ups since last visit
|
4 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: intercurrent flare-ups since last visit
|
4 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: intercurrent flare-ups since last visit
|
0 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: slightly worse movement
|
7 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: moderately worse movement
|
5 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: severely worse movement
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: better movement
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: same movement
|
17 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: slightly worse movement
|
10 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: severely worse movement
|
0 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: better movement
|
0 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: same movement
|
7 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: slightly worse movement
|
7 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: moderately worse movement
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: severely worse movement
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: better movement
|
0 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: same movement
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: slightly worse movement
|
3 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: moderately worse movement
|
0 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: severely worse movement
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 6: bone formation
|
5 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 12: bone formation
|
5 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 18: bone formation
|
1 Participants
|
|
Number of Participants With Flare-ups and Flare-up Outcomes
Month 24: bone formation
|
0 Participants
|
SECONDARY outcome
Timeframe: Months 6, 12, 18 and 24Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
Number of participants with flare-ups by body locations including shoulder, elbow, hip, knee, ankle or foot, back, jaw and submandibular area and other (includes all other locations than mentioned) is presented.
Outcome measures
| Measure |
Palovarotene
n=59 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Number of Participants With Flare-ups by Body Location
Month 6: shoulder
|
8 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: elbow
|
3 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: hip
|
5 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: knee
|
5 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: ankle or foot
|
3 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: back
|
4 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: jaw and submandibular area
|
4 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 6: other
|
14 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: shoulder
|
4 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: elbow
|
2 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: hip
|
5 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: knee
|
3 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: ankle or foot
|
5 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: back
|
2 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: jaw and submandibular area
|
3 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 12: other
|
12 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: shoulder
|
4 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: elbow
|
1 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: hip
|
3 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: knee
|
2 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: ankle or foot
|
2 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: back
|
1 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: jaw and submandibular area
|
0 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 18: other
|
8 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: shoulder
|
1 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: elbow
|
0 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: hip
|
0 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: knee
|
1 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: ankle or foot
|
1 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: back
|
0 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: jaw and submandibular area
|
0 Participants
|
|
Number of Participants With Flare-ups by Body Location
Month 24: other
|
2 Participants
|
SECONDARY outcome
Timeframe: Months 6, 12, 18 and 24Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study. Only those participants with data collected at specified timepoints are reported.
Duration of flare-up was defined as (date of end of flare-up - date of start of flare-up + 1).
Outcome measures
| Measure |
Palovarotene
n=27 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Duration of Flare-up at Months 6, 12, 18 and 24
Month 6
|
130.7 days
Standard Deviation 153.3
|
|
Duration of Flare-up at Months 6, 12, 18 and 24
Month 12
|
121.7 days
Standard Deviation 102.7
|
|
Duration of Flare-up at Months 6, 12, 18 and 24
Month 18
|
72.4 days
Standard Deviation 42.6
|
|
Duration of Flare-up at Months 6, 12, 18 and 24
Month 24
|
72.3 days
Standard Deviation 53.9
|
SECONDARY outcome
Timeframe: Months 6, 12, 18 and 24Population: The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
Percentage of participants with at least 1 extra bone growth associated or not with a flare-up since last visit is presented.
Outcome measures
| Measure |
Palovarotene
n=59 Participants
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 6: associated
|
8.5 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 6: not associated
|
3.4 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 12: associated
|
8.5 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 12: not associated
|
8.5 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 18: associated
|
1.7 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 18: not associated
|
3.4 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 24: associated
|
0 percentage of participants
|
|
Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
Month 24: not associated
|
3.4 percentage of participants
|
Adverse Events
Palovarotene
Serious events: 9 serious events
Other events: 45 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Palovarotene
n=59 participants at risk
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Infections and infestations
Pneumonia
|
3.4%
2/59 • Number of events 2 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
COVID-19
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
Influenza
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
Lower respiratory tract infection
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
Sepsis
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
General disorders
Condition aggravated
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Investigations
SARS-CoV-2 test positive
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Musculoskeletal and connective tissue disorders
Callus formation delayed
|
1.7%
1/59 • Number of events 2 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Vascular disorders
Lymphoedema
|
1.7%
1/59 • Number of events 1 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
Other adverse events
| Measure |
Palovarotene
n=59 participants at risk
Participants continued to receive palovarotene 5 mg orally once daily until it was reimbursed in the country where the study was being conducted or another access program became available or until the study end date, whichever occurred first, up to approximately 32 months.
In case of flare-up symptoms or substantial high risk traumatic events (likely to lead to a flare-up), participants received palovarotene 20 mg orally once daily for 4 weeks followed by 10 mg orally once daily for 8 weeks for a total of 12 weeks even if symptoms resolved earlier.
|
|---|---|
|
Infections and infestations
COVID-19
|
18.6%
11/59 • Number of events 11 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.5%
5/59 • Number of events 5 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
Localised infection
|
5.1%
3/59 • Number of events 3 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
3/59 • Number of events 4 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
23.7%
14/59 • Number of events 16 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.5%
5/59 • Number of events 6 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
6.8%
4/59 • Number of events 5 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.8%
4/59 • Number of events 4 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.8%
4/59 • Number of events 6 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
6.8%
4/59 • Number of events 4 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
5.1%
3/59 • Number of events 5 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
5.1%
3/59 • Number of events 3 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Injury, poisoning and procedural complications
Fall
|
16.9%
10/59 • Number of events 12 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
11.9%
7/59 • Number of events 8 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Injury, poisoning and procedural complications
Extraskeletal ossification
|
6.8%
4/59 • Number of events 6 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
General disorders
Oedema peripheral
|
6.8%
4/59 • Number of events 6 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.9%
7/59 • Number of events 9 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.2%
6/59 • Number of events 8 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.5%
5/59 • Number of events 7 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Gastrointestinal disorders
Lip dry
|
6.8%
4/59 • Number of events 4 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Respiratory, thoracic and mediastinal disorders
Lung diffusion disorder
|
5.1%
3/59 • Number of events 4 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Vascular disorders
Lymphoedema
|
8.5%
5/59 • Number of events 5 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Immune system disorders
Drug hypersensitivity
|
8.5%
5/59 • Number of events 5 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
5.1%
3/59 • Number of events 3 • Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
The FAS/safety set included all participants who received at least 1 dose of palovarotene in this study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place