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NCT03188666: LUMINA-1

A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva

Completed Phase 2 Results posted Last updated 2 December 2022
What this trial tests

Phase 2 trial testing REGN2477 in Fibrodysplasia Ossificans Progressiva in 44 participants. Completed in 16 September 2021.

Timeline
26 February 2018
Primary endpoint
16 September 2019
16 September 2021

Quick facts

Lead sponsorRegeneron Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment44
Start date26 February 2018
Primary completion16 September 2019
Estimated completion16 September 2021
Sites11 locations across France, Italy, Netherlands, United Kingdom, Poland, Canada, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Adults 18 to 60, any sex, with Fibrodysplasia Ossificans Progressiva. 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.

Period 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Primary · Up to Week 28

Treatment-emergent adverse events (TEAEs) are adverse events not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious TEAE was defined as any untoward medical occurrence that resulted in any of following outcomes not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. Num

Participants with at least one TEAE
GroupValue95% CI
Placebo24
REGN2477 10 mg/kg Q4W20
Participants with at least one serious TEAE
GroupValue95% CI
Placebo2
REGN2477 10 mg/kg Q4W4
Period 1: Number of Participants With TEAEs by Severity Primary · Up to Week 28

Severity of TEAEs were graded as follows: Mild: Does not interfere in a significant manner with the participant's normal functioning level. It may be an annoyance. Prescription drugs are not ordinarily needed for relief of symptoms but may be given because of personality of the participants. Moderate: Produces some impairment of functioning but is not hazardous to health. It was uncomfortable or an embarrassment. Treatment for symptom may be needed. Severe: Produces significant impairment of functioning or incapacitation and was a definite hazard to the participant's health. Treatment for symp

GroupValue95% CI
Placebo9
REGN2477 10 mg/kg Q4W7
Placebo12
REGN2477 10 mg/kg Q4W10
Placebo3
REGN2477 10 mg/kg Q4W3
Period 1: Time-Weighted Average (Standardized Area Under the Curve [AUC]) of the Percent Change From Baseline in Total Lesion Activity by Fluorine-18-labeled Sodium Fluoride (18^F-NaF) Positron Emission Tomography (PET) at Week 28 (AHO) Primary · Baseline and Week 28

18\^F-NaF PET is used to assess lesion and disease activity. Time-weighted average (standardized area under the curve \[AUC\]) of the percent change from baseline in total lesion activity by 18\^F-NaF PET up to Week 28 in AHO analysis set is reported.

GroupValue95% CI
Placebo16.6± 9.11
REGN2477 10 mg/kg Q4W-8.1± 9.93
Period 1: Percent Change From Baseline in the Total Volume of HO Lesions as Assessed by Computed Tomography (CT) at Week 28 (AHO) Primary · Week 28

CT is a diagnostic imaging test used to create detailed images of internal organs, bones, soft tissue, and blood vessels. CT scan acquired contemporaneously to the PET scan. Percent change from baseline in the total volume of HO lesions as assessed by CT during Period 1 at Week 28 is reported.

GroupValue95% CI
Placebo32.0± 18.66
REGN2477 10 mg/kg Q4W7.1± 20.43
Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) Primary · Week 28, Week 56

CT is a diagnostic imaging test used to create detailed images of internal organs, bones, soft tissue, and blood vessels. CT scan acquired contemporaneously to the PET scan. HO detectable by CT that developed after baseline are referred to as "new HO lesions." Number of new HO lesions as assessed by CT at Week 56 relative to Week 28 scan is reported.

GroupValue95% CI
Placebo/REGN2477 10 mg/kg Q4W0
Period 1: Time-weighted Average (Standardized AUC) of the Percent Change From Baseline in Total Lesion Activity Assessed by 18^F-NaF PET at Week 28 (AHOC) Primary · Week 28

18\^F-NaF PET is used to assess lesion and disease activity. Time-weighted average (Standardized AUC) of the percent change from baseline in total lesion activity as assessed by 18\^F-NaF PET in Active HO Classic ACVR1 Mutation (AHOC) analysis set up to Week 28 is reported.

GroupValue95% CI
Placebo17.6± 9.73
REGN2477 10 mg/kg Q4W-8.0± 10.14
Period 1: Percent Change From Baseline in the Total Volume of HO Lesions as Assessed by CT at Week 28 (AHOC) Primary · Week 28

CT is a diagnostic imaging test used to create detailed images of internal organs, bones, soft tissue, and blood vessels. CT scan acquired contemporaneously to the PET scan. Percent change from baseline in the total volume of HO lesions was assessed by CT at Week 28 in AHOC analysis set is reported.

GroupValue95% CI
Placebo34.9± 19.90
REGN2477 10 mg/kg Q4W7.0± 20.87
Period 1: Time-weighted Average (Standardized AUC) of the Change From Baseline in Daily Pain Due to Fibrodysplasia Ossificans Progressiva (FOP) Assessed by Daily Numeric Rating Scale (NRS) at Week 28 (AHO) Secondary · Week 28

The pain NRS is a patient reported outcome (PRO) used by participants to rate their pain associated with FOP. Participants were asked to rate their pain on a scale that ranges from "0" (no pain) to "10" (worst possible pain), where the highest score indicated worst outcome. Time-weighted average (Standardized AUC) of the change from baseline in daily pain due to FOP assessed by daily NRS at Week 28 in AHO analysis set is reported.

GroupValue95% CI
Placebo-0.17± 0.205
REGN2477 10 mg/kg Q4W-0.51± 0.231
Period 1: Time-weighted Average (Standardized AUC) of the Change From Baseline in Daily Pain Due to FOP, Assessed by Daily NRS at Week 28 (AHOC) Secondary · Week 28

The pain NRS is a PRO used by participants to rate their pain associated with FOP. Participants were asked to rate their pain on a scale that ranges from "0" (no pain) to "10" (worst possible pain), where the highest score indicated worst outcome. Time-Weighted average (standardized AUC) of the change from baseline in daily pain due to FOP assessed by daily NRS at Week 28 in AHOC analysis set is reported.

GroupValue95% CI
Placebo-0.12± 0.221
REGN2477 10 mg/kg Q4W-0.48± 0.237
Period 1: Percent Change From Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) Assessed by 18^F-NaF PET at Week 8 (AHOC) Secondary · Week 8

Standardized uptake value max (SUVmax) was a measurement of the maximum radiopharmaceutical uptake within the volume of interest. Relative accuracy of a particular radiotracer in a particular tissue is determined by expressing the absolute accuracy (obtained in the primary outcome measure) in terms of percent difference between SUVmax values obtained from PET/CT. Percent Change in 18\^F-NaF SUVmax of Individual Active HO Site(s) assessed by 18\^F-NaF PET in AHOC analysis set is reported.

GroupValue95% CI
Placebo-6.7± 28.79
REGN2477 10 mg/kg Q4W-21.6± 30.25
Period 1: Percent Change From Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) as Assessed by 18^F-NaFPET at Week 8 (AHO) Secondary · Week 8

Percent change in 18\^F-NaF SUVmax of individual active HO site(s) as assessed by 18\^F-NaF PET at Week 8 in AHO analysis set is reported.

GroupValue95% CI
Placebo-7.9± 28.80
REGN2477 10 mg/kg Q4W-21.6± 30.25
Period 1: Change From Baseline in Number of HO Lesions as Assessed by 18^F-NaF PET at Week 28 (AHOC) Secondary · Week 28

Change from baseline in number of HO lesions was assessed by 18\^F-NaF PET at Week 28 in AHOC analysis set is reported.

GroupValue95% CI
Placebo-1.0± 2.66
REGN2477 10 mg/kg Q4W-2.3± 2.24

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug to end of study. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 2/24 (8%)
Deaths: 0/24
REGN2477 10 mg/kg Q4W
Serious: 4/20 (20%)
Deaths: 0/20
Placebo/REGN2477 10 mg/kg Q4W
Serious: 6/24 (25%)
Deaths: 2/24
REGN2477/REGN2477 10 mg/kg Q4W
Serious: 7/19 (37%)
Deaths: 3/19

Serious adverse events (23 terms)

ReactionSystemPlaceboREGN2477 10 mg/kg Q4WPlacebo/REGN2477 10 mg/kg …REGN2477/REGN2477 10 mg/kg…
GastroenteritisInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
AbscessInfections and infestations
Abscess limbInfections and infestations
Gastroenteritis viralInfections and infestations
Perineal abscessInfections and infestations
Perirectal abscessInfections and infestations
Respiratory tract infection viralInfections and infestations
Subcutaneous abscessInfections and infestations
Intestinal obstructionGastrointestinal disorders
Crohn's diseaseGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Head injuryInjury, poisoning and procedural complications
Skull fractureInjury, poisoning and procedural complications
Splenic ruptureInjury, poisoning and procedural complications
Joint swellingMusculoskeletal and connective tissue disorders
Cerebrovascular accidentNervous system disorders
Renal colicRenal and urinary disorders
Other adverse events (225 terms — click to expand)

ReactionSystemPlaceboREGN2477 10 mg/kg Q4WPlacebo/REGN2477 10 mg/kg …REGN2477/REGN2477 10 mg/kg…
MadarosisSkin and subcutaneous tissue disorders
AcneSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
NasopharyngitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
DiarrhoeaGastrointestinal disorders
Post-traumatic painInjury, poisoning and procedural complications
AlopeciaSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
Neck painMusculoskeletal and connective tissue disorders
Spinal painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders
HypertrichosisSkin and subcutaneous tissue disorders
Abscess limbInfections and infestations
RhinitisInfections and infestations
ToothacheGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Joint swellingMusculoskeletal and connective tissue disorders
ErythemaSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Skin lesionSkin and subcutaneous tissue disorders
HirsutismSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Anal abscessInfections and infestations
FolliculitisInfections and infestations
FuruncleInfections and infestations
ParonychiaInfections and infestations
Subcutaneous abscessInfections and infestations
Aphthous ulcerGastrointestinal disorders
VomitingGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Peripheral swellingGeneral disorders
ContusionInjury, poisoning and procedural complications

Most-reported serious reactions: Gastroenteritis, Pneumonia, Sepsis, Urinary tract infection, Abscess, Abscess limb, Gastroenteritis viral, Perineal abscess.

Data from ClinicalTrials.gov NCT03188666 adverse events section.

Sponsor's own description

This is a three period study design consisting of a 6-month, randomized, double-blind placebo-controlled treatment (period 1) followed by a 6-month, open-label treatment (period 2) and a follow-up treatment period (period 3). Primary safety objective of the study is to assess the safety and tolerability of REGN2477 in male and female patients with fibrodysplasia ossificans progressiva (FOP). Primary efficacy objective of the study is to assess the effect of REGN2477 versus placebo on the change from baseline in heterotopic ossification (HO) in patients with FOP, as determined by 18-NaF uptake in HO lesions by positron emission tomography (PET) and in total volume of HO lesions by computed tomography (CT). Key Secondary objectives are: * To compare the effect of REGN2477 versus placebo on pain due to FOP, as measured by the area under the curve (AUC) for pain based on daily pain numeric rating scale (NRS) scores * To assess the effect of REGN2477 versus placebo on the change from baseline in HO, as determined by the number of new HO lesions identified by 18F-NaF PET or by CT * To assess the effect of REGN2477 versus placebo on the change from baseline in 18F-NaF standardized uptake value maximum (SUVmax) of individual active HO site(s) by PET * To assess the effect of REGN2477, between week 28 and week 56, on the number, activity, and volume of HO lesions identified by 18F-NaF PET or by CT in patients who switch from placebo to REGN2477 at week 28 versus the same patients between baseline and week 28 * To assess the effect of REGN2477 versus placebo on the change from baseline in biochemical markers of bone formation * To characterize the concentrations of total activin A at baseline and over time following the first dose of study drug * To characterize the concentration-time profile (pharmacokinetics \[PK\]) of REGN2477 in patients with FOP * To assess the immunogenicity of REGN2477

Publications & conference data

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

  1. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  2. Sarcopenia and Muscle Aging: A Brief Overview.
    Dao T, Green AE, Kim YA, Bae SJ, et al · · 2020 · cited 156× · PMID 33397034 · DOI 10.3803/enm.2020.405
  3. Osteoimmunology: A Current Update of the Interplay Between Bone and the Immune System.
    Guder C, Gravius S, Burger C, Wirtz DC, et al · · 2020 · cited 120× · PMID 32082321 · DOI 10.3389/fimmu.2020.00058
  4. Receptor binding competition: A paradigm for regulating TGF-β family action.
    Martinez-Hackert E, Sundan A, Holien T. · · 2021 · cited 66× · PMID 33087301 · DOI 10.1016/j.cytogfr.2020.09.003
  5. Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop.
    Aykul S, Corpina RA, Goebel EJ, Cunanan CJ, et al · · 2020 · cited 61× · PMID 32515349 · DOI 10.7554/elife.54582
  6. The obligatory role of Activin A in the formation of heterotopic bone in Fibrodysplasia Ossificans Progressiva.
    Alessi Wolken DM, Idone V, Hatsell SJ, Yu PB, et al · · 2018 · cited 54× · PMID 28629737 · DOI 10.1016/j.bone.2017.06.011
  7. Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification.
    Matsuo K, Chavez RD, Barruet E, Hsiao EC. · · 2019 · cited 47× · PMID 31721068 · DOI 10.1007/s11914-019-00541-x
  8. Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva.
    Wentworth KL, Masharani U, Hsiao EC. · · 2019 · cited 39× · PMID 30501012 · DOI 10.1111/bcp.13823

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03188666.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing