A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, then Dose Expansion, in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment

Inclusion Criteria for Patients Previously Treated with SRP-5051.
Patients previously treated with SRP-5051 must meet all of the following
criteria to participate in this study:
I1. Has received prior SRP-5051 treatment in Part A of this study or in Study
5051-102.
I2. If sexually active, agrees to use a male condom during such activity for
the entire duration of the study and for 90 days after the last dose of study
drug. The sexual partner must also use a highly effective form of contraceptive
(refer to Appendix 1 of the protocol for guidance on highly effective
contraceptive methods) during this timeframe.
I3. Is willing to provide informed consent or informed assent (if applicable)
and has (a) parent(s) or legal guardian(s) who is (are) willing to provide
written informed consent for the patient to participate in the study.

Inclusion Criteria for Patients Treatment-Naïve to SRP-5051 Patients who are
treatment-naïve to SRP-5051 must meet all of the following criteria to
participate in this study:
I1. Is male.
I2. Is 7 to 21 years of age, inclusive.
I3. Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the
DMD gene amenable to exon 51-skipping treatment.
I4. Has been on a stable dose of oral corticosteroids for at least 12 weeks
prior to study drug administration or has not received corticosteroids for at
least 12 weeks prior to study drug administration.
I 5.Has stable pulmonary function (FVC >= 40% of predicted and no requirement
for nocturnal ventilation as a result of the complications of DMD) that, in the
Investigator*s opinion, is unlikely to decompensate significantly over the
duration of the study. NOTE: patients on nocturnal ventilation because of sleep
apnea, obesity, or other conditions caused by corticosteroid use are allowed to
participate in the study if FVC % predicted is >= 40
I 6. If sexually active,.
I6. If sexually active, agrees to use a male condom during such activity for
the entire duration of the study and for 90 days after the last dose of study
drug. The sexual partner must also use a highly effective form of contraceptive
(refer to Appendix 1 of the protocol for guidance on highly effective
contraceptive methods) during this timeframe.
I7. Is willing to provide informed consent or informed assent (if applicable)
and has (a) parent(s) or legal guardian(s) who is (are) willing to provide
written informed consent for the patient to participate in the study.

Exclusion Criteria for Patients Previously Treated with SRP-5051:
E 1. Has a current infection, or history of an infection within 12 weeks prior
to Day -1 requiring intravenous treatment with an antibiotic, or oral
antibiotics that may affect renal or cardiac function.
E 2. Has a known kidney disease (identified by eGFR [calculated using Schwartz
2012 cystatin C equation] of < 90 mL/min/1.73 m2) or had an acute kidney injury
within 24 weeks prior to Screening.
E 3. Major surgery within 12 weeks prior to Screening, or planned surgery or
procedures that would interfere with the conduct of the study.
E 4. Presence of other clinically significant illness, including cardiac,
pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or
infection or malignancy.
E 5. Any other condition that, in the Investigator's opinion, could interfere
with the patient's participation in the trial, including body weight loss to <
18 kg.
E 6. Inability to comply with the study protocol.
E 7. Is an employee of the Investigator or study center, with direct
involvement in the proposed study or other studies under the direction of that
Investigator or study center, as well as family members of the employees or the
Investigator.
E 8. Any patient who is taking medications that increase the risk of bleeding,
in the Investigator's opinion
E 9. Platelet count < 150 × 10^3/µL.
E 10. Known hypersensitivity to the study drug (ie, SRP-5051) or to any of its
components.
E 11. Has:
a. Hypomagnesemia (< lower limit of normal) at Screening
b. Other abnormal electrolyte values considered clinically significant by the
Investigator upon medical review and in consultation with the Medical Monitor
at Screening;
c. Serum creatinine > upper limit of normal (ULN) at Screening.
E 12. Has quantitative urinalysis or urine microscopy findings above the ULN
for RBCs or WBCs.
E 13. Urine Protein/Creatinine Ratio >= 200 mg/g and UACR >= 30 mg/g OR 24-hour
urine values for protein >= 200 mg/24 hr at Screening and albumin >= 30 mg/24 hr.
(Note that 24-hour urine protein does not need to be performed during screening
if the UPCR/UACR criteria are met).
E 14. GGT > 3 × ULN at Screening
E 15. Is being treated with a proton pump inhibitor, loop diuretic, or thiazide
diuretic at the time of study initiation.
E 16. Treatment with any exon 51-skipping therapy within 4 weeks prior to
Screening, or with any experimental gene therapy for the treatment of DMD at
any time.
For other exclusion criteria please refer to Protocol

Exclusion Criteria for Patients Treatment-Naïve to SRP-5051:
E 1. History of hypomagnesemia within 12 weeks prior to Screening.
For TN Cohort patients entering the study in Part B
E 2. Has body weight < 18 kg.
E 3. Has a diagnosis of diabetes (any type).
E 4. Initiation or change of dosing (except for modifications to accommodate
changes in weight or changes in standard of care) within 12 weeks prior to
Screening for any of the following: angiotensinconverting enzyme inhibitors,
angiotensin receptor-blocking agents, β- blockers, or potassium.
E 5. Requires anti-arrhythmic and/or diuretic therapy for heart failure.
E 6. Has a current infection, or history of an infection within 12 weeks prior
to Day -1 requiring intravenous treatment with an antibiotic, or oral
antibiotics that may affect renal or cardiac function.
E 7.Has a known kidney disease (identified by eGFR [calculated using Schwartz
cystatin C equation] of < 90 mL/min/1.73 m2) or had an acute kidney injury
within 24 weeks prior to Screening.
E 8. Major surgery within 12 weeks prior to Screening, or planned surgery or
procedures that would interfere with the conduct of the study.
E 9. Presence of other clinically significant illness, including cardiac,
pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or
infection or malignancy.
E 10. Any other condition that, in the Investigator's opinion, could interfere
with the patient's participation in the trial.
E 11. Inability to comply with the study protocol.
E 12. Is an employee of the Investigator or study center, with direct
involvement in the proposed study or other studies under the direction of that
Investigator or study center, as well as family members of the employees or the
Investigator.
E 13. Any patient who is taking medications that increase the risk of bleeding,
in the Investigator's opinion
E 14. Platelet count < 150 × 10^3/µL
E 15. Known sensitivity to the study drug (ie, SRP-5051) or to any of its
components
E 16. Has:
a. Hypomagnesemia (< lower limit of normal) at Screening
b. Other abnormal electrolyte values considered clinically significant by the
Investigator upon medical review and in consultation with the Medical Monitor
at Screening;
c. Serum creatinine > upper limit of normal (ULN) at Screening
E 17. Has quantitative urinalysis or urine microscopy findings above the ULN
for RBCs or WBCs
E 18. Urine Protein/Creatinine Ratio >=200 mg/g and UACR >=30mg/g OR 24-hour
urine values for protein >=200mg/24hr and albumin >= 30mg/24hr
For other exclusion criteria please refer to Protocol