Phase 1/2, dose-escalation study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of SPK-3006 in adults with late-onset Pompe disease
- Conditions
- Pompe Disease10027424
- Registration Number
- NL-OMON55024
- Lead Sponsor
- Spark Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 2
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 than 500 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 Section 13 (Appendix 1) for
guidance on reliable contraception and the definition of women of child-bearing
potential (WOCBP);
6. Agree to refrain from blood, plasma, platelets, egg or sperm, and organ
donation after receiving SPK-3006.
1. Have active hepatitis B and/or C;
All candidates must be screened for both active hepatitis B and C, regardless
of prior known history.
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 a nucleic acid test for hepatitis B virus DNA (HBV-DNA viral
assay).A candidate is not eligible if either HbsAg is positive or HBV-DNA is
positive/detectable.
i. A candidate is not eligible if either HBsAg is positive or HBV-DNA is
positive/detectable.
ii. A candidate is eligible if the anti-HBc is positive and both HBsAg and
HBV-DNA are negative, as this would be consistent with a prior infection of
hepatitis B. Anti-HBc must be obtained in all candidates to discriminate
between acute infection and possible reactivation of hepatitis B during the
trial in candidates with no prior history of hepatitis B.
iii. A candidate who is currently undergoing antiviral therapy for chronic
hepatitis B is not eligible.
b. Screening for hepatitis C:
iv. A candidate who is currently undergoing antiviral therapy for chronic
hepatitis C is not eligible.
v. All other candidates, including those who have never been treated or who
have completed antiviral therapy for chronic hepatitis C must have a nucleic
acid test for hepatitis 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 have
completed anti-viral therapy at least 6 months prior to Screening and have a
negative HCV-RNA at Screening.
• Candidates with a documented or self-reported history of hepatitis C must
have a single negative HCV-RNA at Screening.
2. Have significant underlying liver disease. A candidate is not eligible if
any of the following pre-existing diagnoses, which are indicative of
significant underlying liver disease, are present in the medical record:
• Liver cirrhosis;
• Portal hypertension; or
• Hepatic encephalopathy
• Gamma-glutamyl transferase (GGT) >1.2X upper limit of normal (ULN) adjusted
for age and gender; or
• Bilirubin >1.2X ULN adjusted for age and gender. Candidates with asymptomatic
elevated bilirubin (e.g., Gilbert syndrome) can be considered after discussion
with the Sponsor Medical Monitor.
All candidates who do not have the pre-existing diagnoses listed above must
have the following assessments performed at screening:
• Measurement of serum albumin. A candidate is not eligible if the serum
albumin level is below the testing laboratory*s lower limit of normal;
• Liver fibrosis >= stage 3. The following results are indicative of fibrosis >=
stage 3 and exclude the candidate from participation:
- FibroScan, with a score > 8.3 kPa units
- FibroTest/ FibroSURE with a result > 0.48
- AST-Platelet Ratio Index (APRI) >1;
Of note, if results from more than one modality for evaluation of liver
fibrosis are available (e.g., results from both FibroScan and FibroSURE are
available) the result from FibroScan should be consulted for determination of
liver fibrosis as it will take precedence over other modalities.Human
immunodeficiency virus infection;
3. Have human immunodeficiency virus (HIV) inf
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>3.4 Primary Endpoints<br /><br>The primary endpoints of this study include the following:<br /><br>• Incidence of adverse and serious adverse events (AEs/SAEs), clinically<br /><br>significant abnormal laboratory values, change in vital signs, change in<br /><br>physical examination (PE), vector shedding in bodily fluids, and liver function<br /><br>tests<br /><br>• Immune responses against the AAV capsid (neutralizing antibody [NAb] assay)<br /><br>and GAA transgene product (binding and NAb assays)</p><br>
- Secondary Outcome Measures
Name Time Method