A Study to Evaluate the Safety and Tolerability of GEN6050X in Duchenne Muscular Dystrophy.

Last updated: July 4, 2024
Sponsor: Peking Union Medical College Hospital
Overall Status: Active - Recruiting

Phase

1

Condition

N/A

Treatment

GEN6050X intravenous injection

Clinical Study ID

NCT06392724
GATx-01-IIT-CLINC
  • Ages 4-10
  • Male

Study Summary

The study will evaluate the safety and tolerability of GEN6050X gene therapy in Duchenne muscular dystrophy (DMD) patients amenable to exon 50 skipping.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Subject age: 4-10 years old (including 10 years old)

  2. Gender: Male

  3. Patients with DMD gene exon deletion types confirmed by molecular diagnosis: 8-49, 20-49, 22-49, 51, 51-53, 51-55, 51-57, 51-59, 51-60, 51-67, 51-69, 51-75 or 51-78and other mutations amenable to exon 50 skipping.

  4. The participant is able to walk independently and completes the 10-meter walk testwithout assistance.

  5. Participant is able to complete time to stand from supine independently in less than 30s.

  6. The participant is able to cooperate with motor assessment testing.

  7. Receipt of glucocorticoids for 6 months and a stable daily dose for at least 12weeks prior to study entry

  8. Ability to tolerate muscle biopsies under anesthesia with no contraindications tothese procedures.

Exclusion

Exclusion Criteria:

  1. Participants are in the active period of viral infection, including infections suchas TORCH virus, Epstein-Barr(EB) virus, and severe acute respiratory syndromecoronavirus 2 (SARS-COV-2).

  2. Received a live attenuated vaccine within 3 months prior to receiving GEN6050X, orwas exposed to an influenza (or other inactivated) vaccine within 30 days prior toreceiving GEN6050X, or received systemic antiviral, anti-infective, and/orinterferon therapy.

  3. Serological tests found HIV, Hepatitis B Virus(HBV), hepatitis C virus(HCV), andsyphilis infection.

  4. Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeksprior to receiving gene therapy.

  5. With clear symptoms of cardiomyopathy, echocardiography shows that the leftventricular ejection fraction is less than 40%.

  6. Need for continuous or intermittent assisted support from a ventilator.

  7. Diagnosed with autoimmune disease or receiving related treatment for autoimmunedisease.

  8. The following indicators are abnormal in laboratory biochemical testing:

γ-glutamyl transpeptidase (GGT) above the 2-fold upper limit and total bilirubinabove 1.5 times the upper limit, cystatin C (cystatin C) > 1.27 mg/L, hemoglobin (Hgb) < 100 or >200 g/L; Leukocytes (WBC) > 18.5×10^9/L or platelet ≤ 125×10^9/L.

  1. The titer of AAV9 neutralizing antibody determined by cell suppression assay > 1:50.

  2. Patients have received any gene therapy (e.g., adeno associated virus(AAV) genetherapy), cell therapy (e.g., stem cell transplantation), in vivo editing, or exvivo editing therapy (e.g., CRISPR-Cas9, TALEN) in the past.

  3. Participant has any contraindication to immunosuppressive therapy.

  4. Has a medical condition or extenuating circumstance that, in the opinion of theprincipal investigator, is unsuitable for participation in the clinical trial.

  5. The family does not wish to disclose the patient's study participation to theattending physician and other medical providers.

Study Design

Total Participants: 3
Treatment Group(s): 1
Primary Treatment: GEN6050X intravenous injection
Phase: 1
Study Start date:
July 01, 2024
Estimated Completion Date:
December 31, 2027

Study Description

GEN6050X is an intravenously administered human DMD exon 50 skipping base editing drug containing dual single-stranded adeno-associated virus serotype 9 (ss.AAV9) vectors.

The study is a first-in-human, single-arm, open-label, single-center clinical trial to evaluate safety and tolerability of a single intravenous infusion of GEN6050X in ambulatory boys with DMD. Other objectives include pharmacokinetics, pharmacodynamics, and the preliminary clinical efficacy of GEN6050X over 52 weeks. A total of three ambulatory pediatric participants (aged 4 to 9 years old) are expected to enroll, each receiving a dose of 5×10^13 vg/kg. These participants will be dosed in a staggered fashion.

Safety assessments will include monitoring of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations throughout the study duration. In addition, a comprehensive short-term prophylactic immunosuppression regimen(including rituximab and sirolimus) will be administered prior to treatment in order to mitigate potential immune response.

Connect with a study center

  • Peking Union Medical College Hospital

    Beijing, 100730
    China

    Active - Recruiting

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