A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys with Duchenne Muscular Dystrophy.

The purpose of this study is to find out if a new medicine, RO7239361 can help
people with Duchenne Muscular Dystrophy (DMD). Roche also want to find out if
RO7239361 is safe to take and if it is tolerated well. RO7239361 is not
approved yet.
The efficacy of RO7239361 will be compared to the efficacy of a placebo. DMD is
caused by a mutation in the gene that makes dystrophin. Dystrophin is important
for protecting muscles from stress and damage during activity. In people with
DMD, the body is not able to make enough working dystrophin to protect the
muscles and the muscle mass progressively decreases. RO7239361 is an
anti-myostatin agent able to block myostatin, a protein that is involved in the
regulation of muscle mass. Myostatin has a negative effect on muscle growth and
the muscle mass may increase by blocking myostatin.

Primary
* To compare the efficacy of RO7239361 (BMS-986089) to placebo in ambulatory
boys with Duchenne Muscular Dystrophy.

Secondary

* To compare the efficacy of RO7239361 (BMS-986089) to placebo using the
following tests:
- 4 stair climb velocity (4SCV)
- Stand from supine velocity
- 10 M walk/run velocity
- PODCI transfers and basic mobility subscale
- Proximal lower extremity flexor (knee extension and knee flexion)
strength, measured using manual myometry
- 6-Minute Walk Distance (6MWD)
- Clinical Global Impression of Change (CGI-C)
- Stride velocity recorded with ActiMyo


* To assess the safety and tolerability of RO7239361 in boys with DMD as
reflected by new or worsening lab abnormalities (as defined by CTCAE criteria),
serious adverse events (SAEs) and adverse events (AEs) leading to
discontinuation.

Tertiary/Exploratory
* To assess the safety and tolerability of RO7239361 in boys with DMD as
reflected by vital signs, measures of cardiac function.
* To compare the efficacy of RO7239361 to placebo using the following tests:
- Performance of upper limb (PUL) total score
* To evaluate other measures of efficacy, quality of life and health care
utilization
* To evaluate RO7239361 pharmacokinetics, pharmacodynamics, and immunogenicity
* To explore the effect of genetic variation on target engagement,
pharmacodynamic (PD) effects or functional test endpoints

This is a multi-center, randomized, double-blind, placebo-controlled study.

After completion of the 48 week double blind phase, participants may enter the
open label phase (up to 192 weeks) in which all participants will receive
active RO7239361 study drug.

Each participant will be administered weekly, SC doses of RO7239361 or placebo
for 48 weeks in a randomized, double blind design.

1/3 - RO7239361 dose 1 (7,5 mg of 15 mg based on weight) SC weekly for 48 weeks
double blind
1/3 - RO7239361 dose 2 (35 mg of 50 mg based on weight) SC weekly for 48 weeks
double blind
1/3 - RO7239361 matching placebo SC weekly for 48 weeks double blind

Participants who complete the double blind phase are eligible to receive open
label RO7239361 (active treatment) as part of a 192 week open-label phase of
this study. Doses may be adjusted based on emerging data.

1/2 - RO7239361 dose 1 (7,5 mg of 15 mg based on weight) SC weekly for 192 weeks
1/2 - RO7239361 dose 2 (35 mg of 50 mg based on weight) SC weekly for 192 weeks

RO7239361 7.5 mg dose 10.7 mg/mL (0.7mL/syringe)
RO7239361 15 mg dose 21.4 mg/mL (0.7mL/syringe)
RO7239361 35 mg dose 50 mg/mL (0.7mL/syringe)
RO7239361 50 mg dose 71.4 mg/mL (0.7mL/syringe)
RO7239361 matching placebo 0 mg/mL (0.7mL/syringe)

In the study of healthy adults, the participants received either RO7239361 or
placebo. The most frequent adverse events that occurred in the participants
were injection site redness, upper respiratory tract infection, and injection
site rash. All events were either mild or moderate. The people who experienced
the injection site redness and rash did not have fever and the injection site
redness and rash went away in most cases without treatment.
Some participants also experienced elevations in creatine kinase that did not
last long. Creatine kinase can reflect muscle damage. Creatine kinase is
always elevated in Duchenne patients who are able to walk.
RO7239361 has also been tested in boys with Duchenne. As of 8 February 2018, 43
boys had received doses of RO7239361. The most common adverse events (that is,
occurred in more than one boy), which were considered to be related to study
drug included injection site bruising, redness, irritation or rash and facial
flushing. The skin events were mild to moderate, not associated with fever, and
did not require that study drug be stopped. Some subjects experienced
elevations in creatine kinase and liver enzymes. These elevations are usually
seen in boys with Duchenne who are still able to walk and do not appear to
change with RO7239361 treatment.

It is possible that an allergic reaction may occur in any individual taking a
new drug.

* Subcutaneous Injection of Study drug RO7239361/ or Placebo - Local pain,
bruising, bleeding, blood clot formation, a rash and in rare instances an
infection might occur at the site of injection. There is also the possibility
of dizziness or fainting while your child is being injected. If your child is
prone to this, please inform the study personnel
* Blood Draw - Local pain, bruising, bleeding, blood clot formation, and in
rare instances an infection might occur at the site of the needle stick where
blood is drawn. There is also the possibility of dizziness or fainting while
your child*s blood is being drawn. If your child is prone to this, please
inform the study personnel.
* ECG - The ECG procedure may cause minimal discomfort during the attachment
and removal of the ECG leads to and from the skin. Your child may experience
some skin irritation from the electrode adhesive or develop contact dermatitis
(a skin condition caused by contact between skin and some substance) that may
appear as lighter or darker then the surrounding skin for possibly an extended
period of time.
* ECHO - The echocardiogram procedure may cause minimal discomfort during the
attachment to and removal of the electrodes from the skin.
* DXA Scan - The DXA scan may cause discomfort as your child will need to be
still and may have to hold his breath for a few seconds. The amount of
radiation (energy) is very small - less than one tenth the dose of a chest
x-ray, and less than a day*s exposure to natural radiation.
* Skin biopsy - If your child undergoes a skin biopsy to analyze an injection
site reaction or a rash, the skin to be biopsied will be cleaned and
anesthetized. Once the area is numb, a small piece of skin will be removed
using a punch biopsy instrument. One or two sutures may be required to close
the wound. Antibiotic ointment and a bandage will then be applied. You and
your child will receive instructions for wound care. These should be followed
carefully. Once the anesthetic wears off, the wound may be tender or slightly
painful for a few days. After healing the area of the biopsy may have a small
scar.