AAV2/8-LSPhGAA in Late-Onset Pompe Disease

• ClinicalTrials.gov Identifier: NCT03533673
• Recruitment Status: Recruiting
• First Posted: May 23, 2018
• Last Update Posted: February 21, 2021
• Sponsor: Asklepios Biopharmaceutical, Inc.
• Collaborators: Duke University; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): Asklepios Biopharmaceutical, Inc.

Tracking Information

• First Submitted Date: April 13, 2018
• First Posted Date: May 23, 2018
• Last Update Posted Date: February 21, 2021
• Actual Study Start Date: November 1, 2018
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2018)

• Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability) [ Time Frame: 52 weeks ]
  The incidence of patient reported TEAEs will be measured according to protocol specifications.
• Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability) [ Time Frame: 52 weeks ]
  The incidence of patient reported SAEs will be measured according to protocol specifications.
• Number of Participants With Abnormal Laboratory Values [ Time Frame: 52 weeks ]
  Laboratory assessments will be performed (CBC, Chemistry, urinalysis, serology, anti-GAA antibody, T-cell response, GAA activity) and compared to baseline values.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 21, 2018)

• Muscle GAA Bioactivity [ Time Frame: 12 weeks ]
  Muscle GAA activity will be compared to baseline by muscle biopsy
• Plasma GAA Bioactivity [ Time Frame: 12 weeks ]
  Plasma GAA activity will be compared to baseline by blood screening
• Glycogen content in muscle [ Time Frame: 12 weeks ]
  Muscle glycogen level compared to baseline by muscle biopsy
• Anti-GAA antibody formation [ Time Frame: 52 weeks ]
  Anti-hGAA antibodies monitored by ELISA
• Muscle Status Testing - 6 minute walk test [ Time Frame: 52 weeks ]
  The 6-minute walk test will be performed and results compared to baseline.
• Muscle Status Testing - Gross Motor Function Measure [ Time Frame: 52 weeks ]
  The gross motor function measure (GMFM88) will be performed and the results compared to baseline.
• Muscle Status Testing - Motor Function Measure [ Time Frame: 52 weeks ]
  Measurement of functional motor abilities using the Motor Function Measure (MFM) test will be performed and the results compared with baseline.
• Muscle Status Testing - Gait, Stairs, Gower, Chair [ Time Frame: 52 weeks ]
  The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.
• Pulmonary Function Testing [ Time Frame: 52 weeks ]
  Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.
• Quality of Life Measures - Fatigue Severity Scale [ Time Frame: 52 weeks ]
  Quality of Life measurements using the Fatigue Severity Scale will be taken and results compared to baseline.
• Quality of Life Measures - R-PAct (Rasch-built Pompe specific activity scale) [ Time Frame: 52 weeks ]
  Quality of Life measurements using R-PAct Pompe scale (developed to measure Pompe patients' ability to carry out daily life activities and social participation) will be taken and results compared to baseline.
• Quality of Life Measures - NIH PROMIS [ Time Frame: 52 weeks ]
  Quality of Life measurements using the NIH PROMIS (patient reported outcomes measurement information system) tool will be taken and results compared to baseline.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: AAV2/8-LSPhGAA in Late-Onset Pompe Disease
• Official Title: A Phase 1 Study of the Safety of AAV2/8-LSPhGAA in Late-onset Pompe Disease
• Brief Summary: Open-label, ascending dose trial of AAV2/8-LSPhGAA administered intravenously.
• Detailed Description: This study will be a prospective, open-label trial designed to objectively assess the safety and bioactivity of AAV2/8-LSPhGAA in subjects diagnosed with Pompe disease, which is caused by a defect in acid α-glucosidase (GAA) gene. AAV2/8-LSPhGAA is intended to enable expression of a functional copy of the GAA gene in subject's hepatocytes.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pompe Disease

Intervention

Biological: AAV2/8LSPhGAA

Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.

Study Arms

• Experimental: Cohort 1
  A one-time intravenous infusion of AAV2/8-LSPhGAA (dose level 1)
  Intervention: Biological: AAV2/8LSPhGAA
• Experimental: Cohort 2
  A one-time intravenous infusion of AAV2/8-LSPhGAA (dose level 2)
  Intervention: Biological: AAV2/8LSPhGAA
• Experimental: Cohort 3
  A one-time intravenous infusion of AAV2/8-LSPhGAA (dose level 3)
  Intervention: Biological: AAV2/8LSPhGAA

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 29, 2020): 8
• Original Estimated Enrollment (submitted: May 21, 2018): 6
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

1. Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to receiving ACTUS-101.
2. Intrauterine device in place for at least 90 days prior to receiving ACTUS-101.
3. Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving ACTUS-101.
4. 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.
5. Surgical sterilization of partner(s) (vasectomy) for > 180 days prior toACTUS-101.
6. 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:

1. Must agree to use a condom from Study Day 1 through 6 months after the time of receiving ACTUS-101.
2. Must agree not to donate sperm for 6 months after the time of receiving ACTUS-101.
3. Documented evidence of vasectomy in males for 180 days minimum prior to receiving ACTUS-101 is an acceptable form of contraception.
4. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Edward Smith, MD; 919-613-6832; edward.smith@duke.edu

Contact: Ming Xu, RN; 919-681-1945; mingfen.xu@duke.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03533673
• Other Study ID Numbers: ACT-CS101; 1U01AR071693-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Asklepios Biopharmaceutical, Inc.
• Study Sponsor: Asklepios Biopharmaceutical, Inc.

Collaborators

• Duke University
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Edward C Smith, MD; Duke University

• PRS Account: Asklepios Biopharmaceutical, Inc.
• Verification Date: January 2021