A study of safety, tolerability and efficacy of a single intravenous infusion of SPK-3006 in adults with late-onset Pompe disease (type II glycogen storage disease)
- Conditions
- Pompe Disease (also known as glycogen storage disease type II)MedDRA version: 20.1Level: PTClassification code 10053185Term: Glycogen storage disease type IISystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2019-001283-30-DE
- Lead Sponsor
- Spark Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 20
To be eligible for participation in this study, candidates must meet the following inclusion criteria at Screening/baseline:
1. Be able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations;
2. Are male or female =18 years of age with a confirmed diagnosis (e.g., GAA genetic testing)of LOPD, or based on a documented deficiency of GAA enzyme activity;
3. Have received a marketed ERT for at least the previous 24 months and maintained a stable dose, frequency and compliance for the past 6 months with no dose variation and no longer improving on ERT;
4. Have clinically moderate LOPD characteristics;
a. Be able to walk =75 meters on the 6MWT (assistive devices permitted) but less than500 meters assessed at two timepoints prior to initiating immunosuppression (Day -6)with <10% variance between the assessments. If the variance is =10%, a third timepoint will be collected;
b. Have a percentage of the predicted FVC =30% and =80% in the upright position;
5. Agree to use reliable contraception for a minimum of 6 months after administration of SPK-3006 or 12 weeks after the final dose of sirolimus, whichever occurs later. Female candidates of child-bearing potential must have a negative pregnancy test prior to initiating immunosuppression (Day -6) and on Day 0 prior to administration of SPK-3006. See Section13 (Appendix 1) for guidance on reliable contraception and the definition of women of childbearing potential (WOCBP);
6. Agree to refrain from blood, plasma, platelets, egg or sperm, and organ donation after receiving SPK-3006.[PLEASE REFER TO PROTOCOL SYNOPSYS]
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Candidates will be excluded from study entry if any of the following existat Screening:1. Have active hepatitis B and/or C;All candidates must be screened for both active hepatitis B and C, regardless of prior knownhistory.a. Screening for hepatitis B:All candidates must have a single sample at Screening for each of the following tests:hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (anti-HBc), and anucleic acid test for hepatitis B virus DNA (HBV-DNA viral assay).i. A candidate is not eligible if either HBsAg is positive or HBV-DNA ispositive/detectable.ii. A candidate is eligible if the anti-HBc is positive and both HBsAg and HBV-DNA arenegative, as this would be consistent with a prior infection of hepatitis B.Anti-HBcmust be obtained in all candidates to discriminate between acute infection and possiblereactivation of hepatitis B during the study in candidates with no prior history ofhepatitis B.iii. A candidate who is currently undergoing antiviral therapy for chronic hepatitis B isnot eligible.b. Screening for hepatitis C:i. A candidate who is currently undergoing antiviral therapy for chronic hepatitis C isnot eligible.ii. All other candidates, including those who have never been treated or who havecompleted antiviral therapy for chronic hepatitis C, must have a nucleic acid test forhepatitis C viral RNA (HCV-RNA single load assay) at Screening.• A candidate is not eligible if the HCV-RNA load assay is positive/detectable.• Candidates treated with anti-viral therapy for chronic hepatitis C, must havecompleted anti-viral therapy at least 6 months prior to Screening and have anegative HCV-RNA at Screening.• Candidates with a documented or self-reported history of hepatitis C must have asingle negative HCV-RNA at Screening.2. Have significant underlying liver disease. A candidate is not eligible if any of the followingpre-existing diagnoses, which are indicative of significant underlying liver disease, arepresent in the medical record:• Liver cirrhosis;• Portal hypertension;• Hepatic encephalopathy;Gamma-glutamyl transferase (GGT) >1.2X ULN; or• Bilirubin >1.2X ULN. Candidates with asymptomatic elevated bilirubin (e.g., Gilbertsyndrome) can be considered after discussion with the Sponsor Medical Monitor.All candidates who do not have the pre-existing diagnoses listed above must have thefollowing assessments performed at Screening Visit:• Measurement of serum albumin. A candidate is not eligible if the serumalbumin level isbelow the testing laboratory's lower limit of normal;• Liver fibrosis = stage 3. The following results are indicative of fibrosis = stage 3 andexclude the candidate from participation (see Steatosis Grade table below):FibroScan,with a score >8.3 kPa units if the patient has mild steatosis (Grade S1)FibroScan,with a score >9.5 kPa units if the patient has moderate steatosis(Grade S2)FibroScan, with a score >11 kPa units if the patient has severe steatosis (Grade S3)FibroTest/FibroSURE with a result >0.48AST-Platelet Ratio Index (APRI) >1; this is calculated using the following industrystandard formulation: ([AST in IU/L/AST ULN in IU/L] x 100) / (plateletcount in109/L) (Wai, 2003)NOTE: FibroScan results can be confounded by steatosis of the liver or the candidatebeing overweight. Therefore, all three tests are required to confirm the liver fibrosisstage.3. Have human immunodeficiency virus (HIV) infection;4. Have a prior hypersensitivity to rhGAA;5. Have pre-existing anti-AAV-Spark100 NAb titer
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method