The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports a range of clinical trials studying new and existing interventions for prevention and treatment of arthritis, musculoskeletal, and skin diseases.  Recruitment for this clinical trial complete.   Updates will be made  to this page when the study completes data analysis and results become available. Please check back often and find out how these studies have contributed to generating new knowledge about diseases and conditions within the NIAMS mission area.

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Study Description

The development of gene therapy has advanced to a point where a cure for Pompe disease can be foreseen. Pompe disease (glycogen storage disease type II; acid maltase deficiency) is a devastating muscle disease resulting from acid alpha-glucosidase (GAA) deficiency in striated and smooth muscle. Despite the availability of enzyme replacement therapy (ERT) with recombinant human (rh) GAA, many patients have poor outcomes including death due to clinically significant anti-GAA antibody response. The limitations of ERT have prompted the preclinical development of gene therapy for Pompe disease. Clinical translation of efficacious gene therapy will greatly advance treatment for Pompe disease by correcting GAA deficiency and suppressing immune responses against rhGAA.

The long-term goal of the study is to develop curative therapy for Pompe disease. Toward this end the investigators have developed gene therapy with an adeno-associated virus (AAV) vector that expresses GAA specifically in the liver accompanied by GAA secretion and receptor-mediated uptake of GAA in the heart and skeletal muscle. It is the central hypothesis that continuous GAA production from a liver depot will surpass the benefits achieved with ERT in Pompe disease.

Aim 1 of the study is to determine the safety of AAV vector-mediated gene therapy in adult subjects with Pompe disease. This Phase 1 clinical trial will follow the design of a successful trial that established safety for AAV vector therapy in hemophilia B.  Aim 2 is to determine the bioactivity of the AAV vector in human subjects with Pompe disease. The vector dosage will surpass the minimal effective dose in the third cohort; therefore, bioactivity and potential efficacy will be monitored. Sensitive endpoints for GAA expression will be evaluated, including immunoblotting for GAA in plasma, GAA and glycogen quantification in muscle, and measurement of a urinary biomarker.


Ages Eligible for Study:           18 Years and older   (Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  No

Inclusion Criteria:

  • Diagnosis of Pompe disease by blood or skin fibroblast GAA assay and two pathogenic variants in the GAA gene,
  • Age: Greater than or equal to 18 years at enrollment.
  • Subjects are capable of giving written informed consent.
  • Able to walk at least 100 meters on the 6MWT (with assistive devices permitted).
  • FVC within the range of 30% to less 90% (inclusive) of predicted in the upright position.
  • Receiving ERT for at least 104 weeks (inclusive) immediately preceding screening and receiving a stable dose of ERT for the 52-week period immediately preceding dosing.

Females of childbearing potential must use at least one of the following acceptable birth control methods throughout the study and for 6 months after dosing with ACTUS-101.

  • Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to receiving ACTUS-101.
  • Intrauterine device in place for at least 90 days prior to receiving ACTUS-101.
  • Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving ACTUS-101.
  • Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving ACTUS-101). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject.
  • Surgical sterilization of partner(s) (vasectomy) for > 180 days prior toACTUS-101.
  • Hormonal contraceptives starting > 90 days prior to receiving ACTUS-101. If hormonal contraceptives are started less than 90 days prior to receiving ACTUS-101, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives

Male subjects:

  • Must agree to use a condom from Study Day 1 through 6 months after the time of receiving ACTUS-101.
  • Must agree not to donate sperm for 6 months after the time of receiving ACTUS-101.
  • Documented evidence of vasectomy in males for 180 days minimum prior to receiving ACTUS-101 is an acceptable form of contraception.
  • Males who claim abstinence as their method of contraception are allowed provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving ACTUS-101. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject

Exclusion Criteria:

  • ELISA positive for anti-AAV8 capsid IgG antibodies (>1:5).
  • Invasive ventilation required or noninvasive ventilation required while awake and upright.
  • FVC <20% of predicted (supine).
  • Invasive ventilation required or noninvasive ventilation required while awake and upright.
  • Clinically relevant illness within two weeks of enrollment including fever > 38.2o C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy.
  • Any condition that would interfere with participation in the study as determined by the principal investigator.
  • Received any live vaccination 4 months prior to study Day 1. (Subjects will also be prohibited from receiving any vaccination within the 4-month period after study Day 1).
  • Pregnant or nursing mothers.
  • Anti-rhGAA IgG with sustained titer >1:12,800 for >6 months at time of enrollment.
  • Serology consistent with exposure to HIV, or serology consistent with active hepatitis A, B or C infection. Any active liver disease.
  • GGT > 1.2x ULN adjusted for age and gender.
  • Bilirubin > 1.2x ULN adjusted for age and gender (unless have a history of Dubin Johnson syndrome).
  • Active infection based upon clinical symptoms.
  • Having started respiratory muscle strength training in the last 6 months prior to study day 1 or having discontinued respiratory muscle strength training in the 6-month period preceding study day 1, or having started respiratory strength training greater than 6 months prior to study day 1 and unwilling to continue for the first year of study participation.
  • Received an investigational drug or participated in another interventional study within 90 days of Study Day 1.

Study Design:

Allocation: Randomized

Intervention Model: Sequential Assignment

Masking: None (Open Label)

Primary Purpose: Treatment

Study Location(s):

Duke University, Durham, North Carolina, United States, 27705

Study Website:

Last Updated: