A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva
Condition: Fibrodysplasia Ossificans Progressiva
MeSH terms: Myositis Ossificans
Intervention: REGN2477; Matching placebo
Intervention description: Pharmaceutical form: liquid product for injection/infusion; Route of administration: Intravenous (IV); Administered during treatment periods 1 and 2.; Pharmaceutical form: Liquid product for injection/infusion; Route of administration: Intravenous (IV); Administered during treatment period 1 only.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Men and women 18 to 60 years of age at screening.

          -  Clinical diagnosis of FOP (based on findings of congenital malformation of the great
             toes, episodic soft tissue swelling, and/or progressive heterotopic ossification
             (HO)).

          -  Confirmation of FOP diagnosis with documentation of any ACVR1 mutation.

          -  FOP disease activity within 1 year of screening visit. FOP disease activity is defined
             as pain, swelling, stiffness, and other signs and symptoms associated with FOP
             flare-ups; or worsening of joint function, or radiographic progression of heterotopic
             ossifications (increase in site or number of HO lesions) with/without being associated
             with flare-up episodes.

          -  Willing and able to undergo PET and CT imaging procedures and other procedures as
             defined in this study.

        Key Exclusion Criteria:

          -  Significant concomitant illness or history of significant illness such as, but not
             limited to cardiac, renal, rheumatologic, neurologic, psychiatric, endocrine,
             metabolic or lymphatic disease, that in the opinion of the study investigator might
             confound the results of the study or pose additional risk to the patient by their
             participation in the study.

          -  Previous history or diagnosis of cancer.

          -  Use of bisphosphonate within 1 year of screening.

          -  Concurrent participation in another interventional clinical study, or a
             non-interventional study with radiographic measures or invasive procedures (e.g.
             collection of blood or tissue samples). Participation in the FOP Connection Registry
             or other studies in which participants complete study questionnaires are allowed.

          -  Treatment with another investigational drug, denosumab, imatinib or isotretinoin in
             the last 30 days or within 5 half-lives of the investigational drug, whichever is
             longer.

          -  Pregnant or breastfeeding women.

          -  Male and women of childbearing potential participants who are unwilling to practice
             highly effective contraception.

        Note: Other protocol defined Inclusion/Exclusion criteria apply