NCT05027802: PIVOINE

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.

Completed Phase 3 Results posted Last updated 22 June 2025

What this trial tests

Phase 3 trial testing Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) in 61 participants. Completed in 30 November 2024.

Timeline

14 March 2022

Primary endpoint
30 November 2024

30 November 2024

Quick facts

Lead sponsor	Ipsen
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	61
Start date	14 March 2022
Primary completion	30 November 2024
Estimated completion	30 November 2024
Sites	13 locations across France, Italy, Sweden, United Kingdom, Argentina, Canada, Australia, Spain

Drugs / interventions tested

• Palovarotene (PALOVAROTENE) — full drug profile →

Conditions studied

• Fibrodysplasia Ossificans Progressiva (FOP) — all drugs for Fibrodysplasia Ossificans Progressiva (FOP) →

Sponsor

Ipsen — full company profile →

Who can join

14 and older, any sex, with Fibrodysplasia Ossificans Progressiva (FOP). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · From signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months

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 con

All TEAEs

Group	Value	95% CI
Palovarotene	54

Serious TEAEs

Group	Value	95% CI
Palovarotene	9

Non-serious TEAEs

Group	Value	95% CI
Palovarotene	53

Serious treatment-related TEAEs

Group	Value	95% CI
Palovarotene	1

Non-serious treatment-related TEAEs

Group	Value	95% CI
Palovarotene	38

Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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

Month 6

Group	Value	95% CI
Palovarotene	0.6	± 1.3

Month 12

Group	Value	95% CI
Palovarotene	1.1	± 2.0

Month 18

Group	Value	95% CI
Palovarotene	1.5	± 2.3

Month 24

Group	Value	95% CI
Palovarotene	1.5	± 2.6

Month 30

Group	Value	95% CI
Palovarotene	2.0	± 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 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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)

Month 6

Group	Value	95% CI
Palovarotene	-0.7	± 3.4

Month 12

Group	Value	95% CI
Palovarotene	1.1	± 4.7

Month 18

Group	Value	95% CI
Palovarotene	1.4	± 5.7

Month 24

Group	Value	95% CI
Palovarotene	1.2	± 5.1

Month 30

Group	Value	95% CI
Palovarotene	2.8	± 7.4

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 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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 sc

Month 6: total score

Group	Value	95% CI
Palovarotene	0.74	± 6.37

Month 12: total score

Group	Value	95% CI
Palovarotene	2.39	± 10.21

Month 18: total score

Group	Value	95% CI
Palovarotene	4.77	± 12.39

Month 24: total score

Group	Value	95% CI
Palovarotene	7.80	± 15.15

Month 30: total score

Group	Value	95% CI
Palovarotene	13.79	± 21.98

Month 6: upper extremities subscore

Group	Value	95% CI
Palovarotene	0.70	± 6.87

Month 12: upper extremities subscore

Group	Value	95% CI
Palovarotene	1.12	± 8.52

Month 18: upper extremities subscore

Group	Value	95% CI
Palovarotene	3.24	± 11.28

Annualized Rate of Healthcare Utilization (HU) in Participants With Fibrodysplasia Ossificans Progressiva Secondary · Up to approximately 32 months

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.

Group	Value	95% CI
Palovarotene	21.7	± 31.4

Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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.

Month 6

Group	Value	95% CI
Palovarotene	1.2	± 5.5

Month 12

Group	Value	95% CI
Palovarotene	-0.7	± 6.8

Month 18

Group	Value	95% CI
Palovarotene	-3.9	± 9.8

Month 24

Group	Value	95% CI
Palovarotene	-1.6	± 5.8

Month 30

Group	Value	95% CI
Palovarotene	-2.8	± 3.8

Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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.

Month 6

Group	Value	95% CI
Palovarotene	1.8	± 5.9

Month 12

Group	Value	95% CI
Palovarotene	-3.1	± 9.6

Month 18

Group	Value	95% CI
Palovarotene	-5.3	± 11.8

Month 24

Group	Value	95% CI
Palovarotene	-3.8	± 6.6

Month 30

Group	Value	95% CI
Palovarotene	-10.0	± 11.1

Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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.

Month 6

Group	Value	95% CI
Palovarotene	0.0163	± 0.0574

Month 12

Group	Value	95% CI
Palovarotene	-0.0323	± 0.1358

Month 18

Group	Value	95% CI
Palovarotene	-0.0137	± 0.0888

Month 24

Group	Value	95% CI
Palovarotene	-0.0365	± 0.0994

Month 30

Group	Value	95% CI
Palovarotene	-0.1268	± 0.1564

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 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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.

Month 6

Group	Value	95% CI
Palovarotene	-1.5	± 7.9

Month 12

Group	Value	95% CI
Palovarotene	-5.3	± 12.6

Month 18

Group	Value	95% CI
Palovarotene	-4.4	± 16.5

Month 24

Group	Value	95% CI
Palovarotene	-4.8	± 11.4

Month 30

Group	Value	95% CI
Palovarotene	-20.0	± 20.3

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 Secondary · Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

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 repr

Month 6: GPH

Group	Value	95% CI
Palovarotene	-0.6	± 4.4

Month 12: GPH

Group	Value	95% CI
Palovarotene	-1.7	± 5.0

Month 18: GPH

Group	Value	95% CI
Palovarotene	-2.9	± 5.0

Month 24: GPH

Group	Value	95% CI
Palovarotene	-1.9	± 5.8

Month 30: GPH

Group	Value	95% CI
Palovarotene	-3.9	± 7.0

Month 6: GMH

Group	Value	95% CI
Palovarotene	-1.0	± 4.8

Month 12: GMH

Group	Value	95% CI
Palovarotene	-1.5	± 6.3

Month 18: GMH

Group	Value	95% CI
Palovarotene	-2.3	± 6.9

Number of Participants With Flare-ups and Flare-up Outcomes Secondary · Months 6, 12, 18 and 24

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.

Month 6: at least 1 flare up since last visit

Group	Value	95% CI
Palovarotene	27

Month 12: at least 1 flare up since last visit

Group	Value	95% CI
Palovarotene	26

Month 18: at least 1 flare up since last visit

Group	Value	95% CI
Palovarotene	15

Month 24: at least 1 flare up since last visit

Group	Value	95% CI
Palovarotene	4

Month 6: intercurrent flare-ups since last visit

Group	Value	95% CI
Palovarotene	7

Month 12: intercurrent flare-ups since last visit

Group	Value	95% CI
Palovarotene	4

Month 18: intercurrent flare-ups since last visit

Group	Value	95% CI
Palovarotene	4

Month 24: intercurrent flare-ups since last visit

Group	Value	95% CI
Palovarotene	0

Number of Participants With Flare-ups by Body Location Secondary · Months 6, 12, 18 and 24

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.

Month 6: shoulder

Group	Value	95% CI
Palovarotene	8

Month 6: elbow

Group	Value	95% CI
Palovarotene	3

Month 6: hip

Group	Value	95% CI
Palovarotene	5

Month 6: knee

Group	Value	95% CI
Palovarotene	5

Month 6: ankle or foot

Group	Value	95% CI
Palovarotene	3

Month 6: back

Group	Value	95% CI
Palovarotene	4

Month 6: jaw and submandibular area

Group	Value	95% CI
Palovarotene	4

Month 6: other

Group	Value	95% CI
Palovarotene	14

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events and deaths were collected from signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Palovarotene

Serious: 9/59 (15%)

Deaths: 2/59

Serious adverse events (15 terms)

Reaction	System	Palovarotene
Pneumonia	Infections and infestations	—
COVID-19	Infections and infestations	—
Influenza	Infections and infestations	—
Lower respiratory tract infection	Infections and infestations	—
Sepsis	Infections and infestations	—
Fibula fracture	Injury, poisoning and procedural complications	—
Humerus fracture	Injury, poisoning and procedural complications	—
Tibia fracture	Injury, poisoning and procedural complications	—
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	—
Lung disorder	Respiratory, thoracic and mediastinal disorders	—
Acute myocardial infarction	Cardiac disorders	—
Condition aggravated	General disorders	—
SARS-CoV-2 test positive	Investigations	—
Callus formation delayed	Musculoskeletal and connective tissue disorders	—
Lymphoedema	Vascular disorders	—

Other adverse events (24 terms — click to expand)

Reaction	System	Palovarotene
Dry skin	Skin and subcutaneous tissue disorders	—
COVID-19	Infections and infestations	—
Fall	Injury, poisoning and procedural complications	—
Skin abrasion	Injury, poisoning and procedural complications	—
Back pain	Musculoskeletal and connective tissue disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Upper respiratory tract infection	Infections and infestations	—
Pruritus	Skin and subcutaneous tissue disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Lymphoedema	Vascular disorders	—
Drug hypersensitivity	Immune system disorders	—
Eczema	Skin and subcutaneous tissue disorders	—
Erythema	Skin and subcutaneous tissue disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Skin exfoliation	Skin and subcutaneous tissue disorders	—
Extraskeletal ossification	Injury, poisoning and procedural complications	—
Oedema peripheral	General disorders	—
Lip dry	Gastrointestinal disorders	—
Localised infection	Infections and infestations	—
Nasopharyngitis	Infections and infestations	—
Decubitus ulcer	Skin and subcutaneous tissue disorders	—
Skin disorder	Skin and subcutaneous tissue disorders	—
Lung diffusion disorder	Respiratory, thoracic and mediastinal disorders	—
Vitamin D deficiency	Metabolism and nutrition disorders	—

Most-reported serious reactions: Pneumonia, COVID-19, Influenza, Lower respiratory tract infection, Sepsis, Fibula fracture, Humerus fracture, Tibia fracture.

Data from ClinicalTrials.gov NCT05027802 adverse events section.

Sponsor's own description

The main objective of this study is to further evaluate the safety and efficacy of palovarotene in adult and paediatric participants with FOP.

The aim of the study is also to ensure treatment continuity to participants who have completed one of the parent studies (Study PVO-1A-301, Study PVO-1A-202 and Study PVO-1A-204) and who, in the investigator's judgement, may benefit from palovarotene therapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent progress in drug development for fibrodysplasia ossificans progressiva.
   Meng X, Wang H, Hao J. · · 2022 · cited 17× · PMID 35536530 · DOI 10.1007/s11010-022-04446-9
2. Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG).
   Brasil S, Allocca M, Magrinho SCM, Santos I, et al · · 2022 · cited 15× · PMID 35955863 · DOI 10.3390/ijms23158725
3. Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.
   Felix-Ilemhenbhio F, Pickering GAE, Kiss-Toth E, Wilkinson JM. · · 2022 · cited 13× · PMID 35805978 · DOI 10.3390/ijms23136983
4. Novel Therapeutic Targets for Fibrodysplasia Ossificans Progressiva: Emerging Strategies and Future Directions.
   Shaikh U, Khan A, Kumari P, Ishfaq A, et al · · 2023 · cited 11× · PMID 37521595 · DOI 10.7759/cureus.42614
5. Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.
   Juan C, Bancroft AC, Choi JH, Nunez JH, et al · · 2024 · cited 10× · PMID 38540768 · DOI 10.3390/biom14030349
6. Navigating the Complex Landscape of Fibrodysplasia Ossificans Progressiva: From Current Paradigms to Therapeutic Frontiers.
   Anwar S, Yokota T, Yokota T. · · 2023 · cited 9× · PMID 38136984 · DOI 10.3390/genes14122162
7. Heterotopic ossification: Current developments and emerging potential therapies.
   Bei M, Cao Q, Zhao C, Xiao Y, et al · · 2025 · cited 7× · PMID 39819765 · DOI 10.1097/cm9.0000000000003244
8. The role of miRNA and lncRNA in heterotopic ossification pathogenesis.
   Pulik Ł, Mierzejewski B, Sibilska A, Grabowska I, et al · · 2022 · cited 6× · PMID 36522666 · DOI 10.1186/s13287-022-03213-3