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

Status:	Recruiting
Healthy:	No
Age Range:	18 - 60
Updated:	11/1/2018
Start Date:	March 1, 2018
End Date:	August 4, 2020
Contact:	Clinical Trials Administrator
Email:	clinicaltrials@regeneron.com
Phone:	844-734-6643

A Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effects on Heterotopic Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva

This is a two 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).

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).

Secondary objectives are:

- 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 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 numeric rating scale (NRS) scores

- 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

Key Inclusion Criteria:

1. Men and women 18 to 60 years of age at screening.

2. Clinical diagnosis of FOP (based on findings of congenital malformation of the great
toes, episodic soft tissue swelling, and/or progressive heterotopic ossification).

3. Confirmation of classic FOP diagnosis with documentation of the ACVR1[R206H] mutation.

4. 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.

5. Willing and able to undergo PET and CT imaging procedures and other procedures as
defined in this study.

Key Exclusion Criteria:

1. 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.

2. Use of bisphosphonate within 1 year of screening.

3. 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 patients complete study questionnaires are allowed.

4. Pregnant or breastfeeding women.

5. Male and women of childbearing potential patients who are unwilling to practice highly
effective contraception.

Note: Other protocol defined Inclusion/Exclusion criteria may apply

We found this trial at

sites

The Mayo Clinic

Rochester, Minnesota 55905

Phone: 507-266-1944

from

Rochester, MN