A Gene Therapy Study of RP-A501 in Male Patients With Danon Disease
ConditionDanon Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age8+
SponsorRocket Pharmaceuticals Inc.
About this trial
This is a single arm Phase 2 trial to evaluate the efficacy and safety of RP-A501, a recombinant adeno-associated virus serotype 9 (rAAV9) vector containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene, in male patients with Danon disease.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.
Male.
Age ≥8 years.
Abnormal thickening of left ventricular wall,
Disqualifiers
Anti-AAV9 neutralizing antibody titer >1:40.
Severe heart failure or requirement for advanced therapies (requirement for intravenous inotropic, vasodilator, or diuretic therapy within the 30 days prior to enrollment, presence or requirement for mechanical circulatory support (MCS), and presence or requirement for mechanical ventilation).
History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina.
Prior cardiac or other organ (lung, liver, other) transplantation.
Trial design
Design model
Single group
Treatments tested in this trial
RP-A501
GeneticRP-A501 is a gene therapy product consisting of an rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single IV infusion. Dose of RP-A501: Cohorts 1, 2 \& 3 = 6.7 x10\^13 genome copies (GC)/kg; Cohort 4 = 3.8 x10\^13 GC/kg. An immunomodulation regimen is initiated before RP-A501 administration to reduce the risk of gene therapy-related complications. The regimen includes rituximab or a biosimilar, administered in two doses for Cohorts 1-3 and three doses for Cohort 4, along with sirolimus and corticosteroids. Pegcetacoplan was incorporated into the immunomodulation regimen for Cohort 3 but excluded in Cohort 4.
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: RP-A501Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Evaluation of Efficacy: Improvement as assessed via primary endpoint comprised of LAMP2 myocardial tissue expression and left ventricular mass index (LVMI)
Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC), AND, ≥ 10% decrease in LVMI from baseline.
Time frame
12 months post-infusionSecondary outcomes
1
Evaluation of efficacy via components of the primary endpoint - LAMP2
Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC)
Time frame
12 months post infusion2
Evaluation of efficacy via components of the primary endpoint - Left Ventricular Mass Index (LVMI)
≥ 10% decrease in LVMI from baseline
Time frame
12 months post infusion3
Evaluation of efficacy via biomarker evidence of myocardial injury - High Sensitivity Troponin I (hsTnI)
≥ 20% decrease in hsTnI from baseline
Time frame
12 months post infusion4
Evaluation of efficacy via biomarker evidence of myocardial injury - N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
≥ 20% decrease in NT-proBNP from baseline
Time frame
12 months post infusionSponsors and contacts
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Source ClinicalTrials.gov