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An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva. (MOVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03312634
Recruitment Status : Completed
First Posted : October 18, 2017
Results First Posted : March 14, 2023
Last Update Posted : November 29, 2023
Sponsor:
Information provided by (Responsible Party):
Ipsen ( Clementia Pharmaceuticals Inc. )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fibrodysplasia Ossificans Progressiva
Intervention Drug: Palovarotene
Enrollment 107
Recruitment Details 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.
Pre-assignment Details This study included 3 parts: Part A, the main part of the study, Part B, the 24-month extension and Part C, up to 2 year post last dose of study treatment follow-up. A total of 107 participants were enrolled and treated in this study. Data from participants in PVO-1A-001 were used as an external control for only primary endpoint of this study. Hence, data for participants in PVO-1A-001 are reported in participant flow, baseline characteristics and adverse events section only.
Arm/Group Title Palovarotene Untreated (PVO-1A-001)
Hide Arm/Group Description Participants were administered 5 milligram (mg) palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks. Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Period Title: Overall Study
Started 107 114
Completed 49 33
Not Completed 58 81
Reason Not Completed
Adverse Event             11             0
Sponsor request             2             0
Withdrawal by Subject             31             9
Enrolled in an interventional study             0             52
Enrolled in an interventional study at time of a flare-up             0             9
Death             0             1
Non-compliance             0             2
Lost to Follow-up             0             1
Enrolled into non-interventional study             0             5
Worsening clinical condition             0             1
Participant did not want to travel             0             1
Physician Decision             1             0
Other             13             0
Arm/Group Title Palovarotene Untreated (PVO-1A-001) Total
Hide Arm/Group Description Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks. Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control. Total of all reporting groups
Overall Number of Baseline Participants 99 114 213
Hide Baseline Analysis Population Description
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 114 participants 213 participants
<=18 years 75 70 145
Between 18 and 65 years 24 44 68
>=65 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 114 participants 213 participants
Female 46 52 98
Male 53 62 115
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 114 participants 213 participants
Hispanic or Latino 19 23 42
Not Hispanic or Latino 69 73 142
Unknown or Not Reported 11 18 29
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 114 participants 213 participants
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
1.Primary Outcome
Title Annualized New Heterotopic Ossification (HO)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Principal FAS includes all enrolled participants in the Principal EP who had a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in study PVO-1A-301. For study PVO-1A-001, the Principal FAS included participants enrolled in study PVO-1A-001 with available baseline and at least 1 post-baseline HO volume measurement. Study PVO-1A-001 was used as an external control.
Arm/Group Title Palovarotene Untreated (PVO-1A-001)
Hide Arm/Group Description:
Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.
Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Overall Number of Participants Analyzed 97 101
Mean (Standard Error)
Unit of Measure: cubic millimeters (mm^3)
9427.1  (3084.0) 23720.2  (4850.0)
2.Secondary Outcome
Title Percentage of Participants With Any New HO
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The Principal FAS included all enrolled participants in the Principal EP who had a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in study PVO-1A-301.
Arm/Group Title Palovarotene
Hide Arm/Group Description:
Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.
Overall Number of Participants Analyzed 97
Measure Type: Number
Unit of Measure: percentage of participants
83.5
3.Secondary Outcome
Title Number of Body Regions With New HO
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The Principal FAS included all enrolled participants in the Principal EP who had a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in the study PVO-1A-301. Only data from the participants analyzed were reported.
Arm/Group Title Palovarotene
Hide Arm/Group Description:
Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.
Overall Number of Participants Analyzed 81
Mean (Standard Deviation)
Unit of Measure: body regions
3.0  (1.68)
4.Secondary Outcome
Title Percentage of Participants With Flare-Ups
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Principal SS included all enrolled participants in the Principal EP set (ie, participants with the R206H ACVR1 mutation) receiving at least 1 dose of palovarotene in study PVO-1A-301. Only data from the participants analyzed at Month 12 reported.
Arm/Group Title Palovarotene
Hide Arm/Group Description:
Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.
Overall Number of Participants Analyzed 99
Measure Type: Number
Unit of Measure: percentage of participants
64.6
5.Secondary Outcome
Title Ratio of Flare-Up Per Participant-Month of Exposure
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301.
Arm/Group Title Palovarotene
Hide Arm/Group Description:
Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.
Overall Number of Participants Analyzed 107
Mean (Standard Deviation)
Unit of Measure: ratio of flare-up
0.2  (0.40)
Time Frame 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.
Adverse Event Reporting Description The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The 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.
 
Arm/Group Title Palovarotene 5 mg Palovarotene 20/10 mg Untreated (PVO-1A-001)
Hide Arm/Group Description Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks. Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control. While no pharmacological intervention was applied in this observational study, safety issues resulting only from any study-related procedure were recorded as AEs.
All-Cause Mortality
Palovarotene 5 mg Palovarotene 20/10 mg Untreated (PVO-1A-001)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/107 (0.00%)      0/81 (0.00%)      1/114 (0.88%)    
Hide Serious Adverse Events
Palovarotene 5 mg Palovarotene 20/10 mg Untreated (PVO-1A-001)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/107 (31.78%)      19/81 (23.46%)      0/114 (0.00%)    
Blood and lymphatic system disorders       
Anemia  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Gastrointestinal disorders       
Abdominal Pain  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
General disorders       
Condition Aggravated  1  2/107 (1.87%)  2 3/81 (3.70%)  3 0/114 (0.00%)  0
Infections and infestations       
Appendicitis  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Bacterial Sepsis  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Cellulitis  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Escherichia Sepsis  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Klebsiella Bacteremia  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Mycoplasma Infection  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Pneumonia  1  1/107 (0.93%)  1 1/81 (1.23%)  1 0/114 (0.00%)  0
Urosepsis  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Corona virus infection  1  10/107 (9.35%)  10 2/81 (2.47%)  2 0/114 (0.00%)  0
Injury, poisoning and procedural complications       
Radius Fracture  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Traumatic Fracture  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Post procedural haematoma  1  1/107 (0.93%)  2 0/81 (0.00%)  0 0/114 (0.00%)  0
Exposure to communicable disease  1  3/107 (2.80%)  3 0/81 (0.00%)  0 0/114 (0.00%)  0
Metabolism and nutrition disorders       
Malnutrition  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Epiphyses Premature Fusion  1  11/107 (10.28%)  11 10/81 (12.35%)  10 0/114 (0.00%)  0
Back Pain  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Epiphyseal Disorder  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Mobility Decreased  1  0/107 (0.00%)  0 1/81 (1.23%)  1 0/114 (0.00%)  0
Aneurysmal bone cyst  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Pain in extremity  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Uterine Leiomyoma  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Nervous system disorders       
Syncope  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Respiratory Distress  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
Vascular disorders       
Lymphoedema  1  1/107 (0.93%)  1 0/81 (0.00%)  0 0/114 (0.00%)  0
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Palovarotene 5 mg Palovarotene 20/10 mg Untreated (PVO-1A-001)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   105/107 (98.13%)      77/81 (95.06%)      0/114 (0.00%)    
Ear and labyrinth disorders       
Ear pain  1  6/107 (5.61%)  7 1/81 (1.23%)  1 0/114 (0.00%)  0
Eye disorders       
Dry Eye  1  8/107 (7.48%)  8 11/81 (13.58%)  14 0/114 (0.00%)  0
Gastrointestinal disorders       
Lip Dry  1  37/107 (34.58%)  38 17/81 (20.99%)  17 0/114 (0.00%)  0
Chapped Lips  1  6/107 (5.61%)  7 10/81 (12.35%)  11 0/114 (0.00%)  0
Vomiting  1  11/107 (10.28%)  14 5/81 (6.17%)  5 0/114 (0.00%)  0
Nausea  1  9/107 (8.41%)  9 3/81 (3.70%)  3 0/114 (0.00%)  0
Cheilitis  1  3/107 (2.80%)  3 8/81 (9.88%)  13 0/114 (0.00%)  0
Diarrhea  1  6/107 (5.61%)  6 2/81 (2.47%)  2 0/114 (0.00%)  0
General disorders       
Peripheral swelling  1  3/107 (2.80%)  3 6/81 (7.41%)  7 0/114 (0.00%)  0
Immune system disorders       
Seasonal Allergy  1  7/107 (6.54%)  8 0/81 (0.00%)  0 0/114 (0.00%)  0
Infections and infestations       
Upper Respiratory Tract Infection  1  23/107 (21.50%)  30 6/81 (7.41%)  7 0/114 (0.00%)  0
Nasopharyngitis  1  14/107 (13.08%)  26 9/81 (11.11%)  12 0/114 (0.00%)  0
Paronychia  1  9/107 (8.41%)  13 10/81 (12.35%)  15 0/114 (0.00%)  0
Ear Infection  1  5/107 (4.67%)  5 6/81 (7.41%)  7 0/114 (0.00%)  0
Otitis Media  1  6/107 (5.61%)  7 3/81 (3.70%)  3 0/114 (0.00%)  0
Gastroenteritis  1  6/107 (5.61%)  8 2/81 (2.47%)  2 0/114 (0.00%)  0
Urinary Tract Infection  1  6/107 (5.61%)  6 1/81 (1.23%)  2 0/114 (0.00%)  0
Influenza  1  7/107 (6.54%)  7 4/81 (4.94%)  4 0/114 (0.00%)  0
Injury, poisoning and procedural complications       
Contusion  1  9/107 (8.41%)  12 6/81 (7.41%)  6 0/114 (0.00%)  0
Skin Abrasion  1  8/107 (7.48%)  11 9/81 (11.11%)  13 0/114 (0.00%)  0
Fall  1  10/107 (9.35%)  12 7/81 (8.64%)  12 0/114 (0.00%)  0
Investigations       
Bone density decreased  1  8/107 (7.48%)  8 5/81 (6.17%)  5 0/114 (0.00%)  0
Alanine aminotransferase increased  1  1/107 (0.93%)  1 5/81 (6.17%)  5 0/114 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  32/107 (29.91%)  49 15/81 (18.52%)  24 0/114 (0.00%)  0
Pain In Extremity  1  21/107 (19.63%)  33 9/81 (11.11%)  13 0/114 (0.00%)  0
Neck Pain  1  6/107 (5.61%)  6 6/81 (7.41%)  9 0/114 (0.00%)  0
Back Pain  1  8/107 (7.48%)  13 3/81 (3.70%)  4 0/114 (0.00%)  0
Musculoskeletal Pain  1  7/107 (6.54%)  9 5/81 (6.17%)  5 0/114 (0.00%)  0
Joint range of motion decreased  1  6/107 (5.61%)  9 3/81 (3.70%)  3 0/114 (0.00%)  0
Pain in jaw  1  6/107 (5.61%)  7 2/81 (2.47%)  2 0/114 (0.00%)  0
Myalgia  1  6/107 (5.61%)  6 2/81 (2.47%)  2 0/114 (0.00%)  0
Nervous system disorders       
Headache  1  10/107 (9.35%)  13 7/81 (8.64%)  7 0/114 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  7/107 (6.54%)  7 5/81 (6.17%)  5 0/114 (0.00%)  0
Epistaxis  1  6/107 (5.61%)  14 3/81 (3.70%)  3 0/114 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dry skin  1  60/107 (56.07%)  95 37/81 (45.68%)  77 0/114 (0.00%)  0
Alopecia  1  19/107 (17.76%)  23 21/81 (25.93%)  28 0/114 (0.00%)  0
Drug eruption  1  15/107 (14.02%)  24 26/81 (32.10%)  40 0/114 (0.00%) 
Pruritus  1  19/107 (17.76%)  29 14/81 (17.28%)  16 0/114 (0.00%)  0
Rash  1  25/107 (23.36%)  40 11/81 (13.58%)  22 0/114 (0.00%)  0
Erythema  1  11/107 (10.28%)  15 16/81 (19.75%)  21 0/114 (0.00%)  0
Skin exfoliation  1  11/107 (10.28%)  14 11/81 (13.58%)  23 0/114 (0.00%)  0
Skin irritation  1  6/107 (5.61%)  9 5/81 (6.17%)  6 0/114 (0.00%)  0
Rash generalized  1  6/107 (5.61%)  9 4/81 (4.94%)  5 0/114 (0.00%)  0
Dermatitis  1  3/107 (2.80%)  3 7/81 (8.64%)  8 0/114 (0.00%)  0
Ingrowing nail  1  6/107 (5.61%)  8 4/81 (4.94%)  5 0/114 (0.00%)  0
Pruritus generalised  1  16/107 (14.95%)  21 11/81 (13.58%)  19 0/114 (0.00%)  0
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
A valid comparison of AEs from observational study (PVO-1A-001) was not made since AEs were only captured as related to study procedures.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Ipsen
Phone: see email
EMail: clinical.trials@ipsen.com
Layout table for additonal information
Responsible Party: Ipsen ( Clementia Pharmaceuticals Inc. )
ClinicalTrials.gov Identifier: NCT03312634    
Other Study ID Numbers: PVO-1A-301
2017-002541-29 ( EudraCT Number )
First Submitted: October 9, 2017
First Posted: October 18, 2017
Results First Submitted: January 20, 2023
Results First Posted: March 14, 2023
Last Update Posted: November 29, 2023