A Study to Assess the Effectiveness and Safety of 2 Dosage Regimens of Oral Fidrisertib (IPN60130) for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP). (FALKON)
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| ClinicalTrials.gov Identifier: NCT05039515 |
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Recruitment Status :
Recruiting
First Posted : September 9, 2021
Last Update Posted : April 29, 2024
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Sponsor:
Clementia Pharmaceuticals Inc.
Collaborator:
Ipsen
Information provided by (Responsible Party):
Ipsen ( Clementia Pharmaceuticals Inc. )
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Brief Summary:
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by the presence of bone in soft tissue where bone normally does not exist, known as Heterotopic Ossification (HO). It is often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to abnormal stiffening and immobility (ankyloses) of major joints with cumulative and irreversible loss of movement and disability.
This study will evaluate the efficacy of 2 dosing regimens of IPN60130 in inhibiting new HO volume compared with placebo (a dummy treatment) in adult and paediatric participants with FOP. It will be assessed by a scan (provides internal images of the body) called low dose Whole Body Computed Tomography (WBCT), excluding head.
Adults and participants 5 years of age or older are also eligible for a sub study to evaluate HO lesions assessed by another type of scan, Fluorine-18-labelled natrium fluoride Positron Emission Tomography-Computed Tomography ([18F]NaF PET-CT ).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Fibrodysplasia Ossificans Progressiva | Drug: IPN60130 Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 98 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Study to Assess the Efficacy and Safety of 2 Dosage Regimens of Oral Fidrisertib (IPN60130) for the Treatment of Fibrodysplasia Ossificans Progressiva in Male and Female Paediatric and Adult Participants. |
| Actual Study Start Date : | December 1, 2021 |
| Estimated Primary Completion Date : | August 30, 2025 |
| Estimated Study Completion Date : | August 30, 2029 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Idiopathic inflammatory myopathy
Fibrodysplasia ossificans progressiva
| Arm | Intervention/treatment |
|---|---|
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Experimental: IPN60130 high dosage
Oral capsule, swallowed whole or sprinkled onto food, once daily
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Drug: IPN60130
Immediate-release capsule containing high dose of the drug substance.
Other Name: Fidrisertib |
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Experimental: IPN60130 low dosage
Oral capsule, swallowed whole or sprinkled onto food, once daily
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Drug: IPN60130
Immediate-release capsule containing low dose of the drug substance.
Other Name: Fidrisertib |
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Placebo Comparator: Placebo
Oral capsule, swallowed whole or sprinkled onto food, once daily
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Drug: Placebo
Placebo will be supplied as powder filled hard capsules |
Primary Outcome Measures :
- Annualized change in HO volume as assessed by low-dose WBCT (excluding the head) in treated participants receiving IPN60130 compared with placebo. [ Time Frame: From baseline to 12 months ]
- Incidence of Adverse Events / Serious Adverse Events (AEs/SAE) [ Time Frame: From baseline until the end of study (63 months) ]
- Change from baseline in clinically significant abnormal values in laboratory parameters (haematology, biochemistry, and urinalysis) [ Time Frame: From baseline until the end of study (63 months) ]Percentage of participants with clinically significant change in laboratory parameters (biochemistry, hematology and urinalysis) will be reported. The clinical significance will be graded by the investigator.
- Change from baseline in physical examination findings [ Time Frame: From baseline until the end of study (63 months) ]Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator.
- Change from baseline in clinically significant vital signs [ Time Frame: From baseline until the end of study (63 months) ]Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.
- Change from baseline in clinically significant Electrocardiogram (ECG) readings [ Time Frame: From baseline until the end of study (63 months) ]Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.
Secondary Outcome Measures :
- Change in HO volume of new HO lesions as detected by WBCT in participants receiving IPN60130 compared with placebo recipients [ Time Frame: From baseline up to 12 months ]
- Change in number of HO lesions by WBCT in participants receiving IPN60130 compared with placebo recipients [ Time Frame: From baseline up to 12 months ]
- Flare-up rate and number of flare-up days in participants receiving IPN60130 compared with placebo recipients [ Time Frame: From baseline up to 12 months ]The rate and the number of flare-up days, the flare-up being confirmed by the Investigator, will be compared between participants treated with IPN60130 and those treated with Placebo at Month 12
- The number of body regions with new HO in participants receiving IPN60130 compared with placebo recipients [ Time Frame: From baseline up to 12 months ]
- Change in pain intensity [ Time Frame: From baseline up to 12 months ]Assessed in participants ≥13 years old with the Numeric pain rating scale (NRS) and in participants <13 years old with Wong Baker Faces Pain Scale (FPS)
- The proportion of participants with any new HO in participants receiving IPN60130 compared with placebo recipients [ Time Frame: From baseline up to 12 months ]
- Change from baseline in HO volume as detected by WBCT in participants receiving IPN60130 compared with placebo recipients and with participants receiving the standard of care in the Natural history study (NHS) [ Time Frame: From baseline up to 60 months ]
- Change from baseline in Cumulative Analogue Joint Involvement Scale for FOP (CAJIS) by treatment arm compared with placebo recipients and participants receiving the standard of care in the NHS across all available timepoints [ Time Frame: From baseline up to 60 months ]
- Change in the FOP Physical Function Questionnaire (FOP-PFQ) by treatment arm compared with placebo recipients and participants receiving the standard of care in the NHS from baseline across all available timepoints [ Time Frame: From baseline up to 60 months ]
- Pharmacokinetic (PK) parameter: Cmax of IPN60130 [ Time Frame: From baseline up to Month 24 ]Cmax is defined as the maximum observed concentration of IPN60130
- PK parameter: AUC of IPN60130 [ Time Frame: Every 6 months up to Month 24 ]AUC is defined as the concentration of drug over time.
- PK parameter: Ctrough of IPN60130 [ Time Frame: Every 6 months up to Month 24 ]Ctrough is defined as the plasma concentration at the end of the dosing interval.
- PK parameter: Cmin of IPN60130 [ Time Frame: Every 6 months up to Month 24 ]Cmin is defined as the minimum observed concentration of IPN60130
- Assessment of the exposure-response relationship [ Time Frame: From baseline up to 60 months ]The exposure-response relationship will be assessed by modelling using relevant efficacy and safety parameters
Information from the National Library of Medicine
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| Ages Eligible for Study: | 5 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Participants must be at least 5 years of age, to be confirmed (entry for younger paediatric participants <15 years of age will only be once safety in adult and older paediatric participants ≥15 years of age has been established) at the time of signing the informed participant/parent consent and, for participants who are minors, age-appropriate assent.
- Participants must be at least 15 years of age at the time of signing the informed participant/parent consent for the main study and, for participants who are minors, age-appropriate assent
- Participants must be clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants associated with progressive HO.
- Participants must have disease progression in the preceding year of the screening visit.
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Participants who have participated in a prior clinical study using another investigational product for the treatment of FOP may be enrolled after a washout of at least 5 half-lives of the other investigational product. Participants with prior treatment such as, but not limited to, imatinib, isotretinoin, garetosmab, or palovarotene may be enrolled 30 days after discontinuation or after washout of at least 5 half-lives, whichever is longer.
- Washout period for palovarotene is 30 days
- Washout period for garetosmab is 4 months
- Participants must be able to perform pulmonary function tests adequately and reliably.
- Participants must be able to have an adequate echocardiography assessment at screening for evaluation of left ventricular structure and function as defined by the protocol.
- Participants must be accessible for treatment and follow-up and be able to undergo all study procedures. Participants living at distant locations from the investigational site must be able and willing to travel to a site for the initial and all on-site follow-up visits. Participants must be able to undergo low-dose WBCT (excluding head) without sedation.
- Body weight ≥10 kg.
- Abstinent or using two highly effective forms of birth control. Females must also have a negative blood or urine pregnancy test prior to administration of study drug.
- Participants must be capable of giving written, signed, and dated informed participant/parent consent; and for participants who are minors, age-appropriate assent and/or legal guardian consent (performed according to local regulations)
Key Exclusion Criteria:
- Participants with complete heart block and left bundle branch block on screening electrocardiogram.
- Participants with screening echocardiography showing septal or left ventricular free wall thickness >12 mm for adult participants or a z-score >3 compared with population norms for children and adolescent participants or left ventricular ejection fraction (LVEF) <50%.
- Participants with severe mitral or tricuspid regurgitation on echocardiography at screening.
- Participants with significant underlying lung disease requiring supplementary oxygen or forced vital capacity <35% of predicted at screening.
- Participants with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or another significant disease as judged by the investigator.
- Participants with severe hepatic impairment.
- Concomitant medications that are strong inhibitors (including grapefruit juice) or inducers (including St John's Wort) of cytochrome P450 (CYP) 3A4 activity; or kinase inhibitors such as imatinib.
- Prior use in the past year and concomitant use of bisphosphonates for participants in the PET-CT sub study.
- Concurrent participation in another interventional clinical study, or a noninterventional study with radiographic measures or invasive procedures (e.g. collection of blood or tissue samples).
- Amylase or lipase >2× the upper limit of normal (ULN) or with a history of chronic pancreatitis.
- Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5×ULN.
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Participants with hematologic abnormalities:
- Hgb<10g/dL
- Platelets<75,000/mm3
- WBC<2000/mm3
- Participants with coagulation test measurements outside of the normal range at screening.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05039515
Contacts
| Contact: Ipsen Clinical Study Enquiries | see email | clinical.trials@ipsen.com |
Locations
Show 37 study locations
Sponsors and Collaborators
Clementia Pharmaceuticals Inc.
Ipsen
Investigators
| Study Director: | Ipsen Medical Director | Ipsen |
| Responsible Party: | Clementia Pharmaceuticals Inc. |
| ClinicalTrials.gov Identifier: | NCT05039515 |
| Other Study ID Numbers: |
D-CA-60130-452 2020-002858-24 ( EudraCT Number ) |
| First Posted: | September 9, 2021 Key Record Dates |
| Last Update Posted: | April 29, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Where patient data can be anonymised, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available. |
| Time Frame: | Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available. |
| Access Criteria: | Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Myositis Ossificans Myositis Muscular Diseases Musculoskeletal Diseases |