Principal Investigator: Nicola Longo
Keywords: Pompe Disease , Glycogen Storage Disease Type 2 , Lumizyme , NeoGAA , COMET Study Department: Pediatric Genetics
IRB Number: 00097168
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Recruiting

Contact Information

Carrie Bailey

Brief Summary

Study Purpose:
Study EFC14028 is being conducted as a Phase 3 multicenter, multinational, randomized, double-blinded study to minimize bias. 
EFC14028 (Comet) study is a head-to-head study design to compare neoGAA directly to alglucosidase alfa (Lumizyme), which is the only available Enzyme Replancement Therapy (ERT) for late onset Pompe Disease (LOPD). The study will be conducted at a dose of 20 mg/kg qow, which is the recommended labeled dose for alglucosidase alfa and is supported based on results from nonclinical studies and the safety and exploratory efficacy results from the phase 1 TDR12857 clinical study as being likely to result in greater glycogen depletion in skeletal muscles and clinical efficacy than alglucosidase alfa without new safety concerns. 
Because neoGAA is expected to be at least as efficacious as alglucosidase alfa, it is considered appropriate to test first for NI and then for superiority.
Primary objective:
The primary objective of the study is to determine the effect of neoGAA treatment on respiratory muscle strength as measured by Forced Vital Capacity (FVC) % predicted in the upright position, as
compared to alglucosidase alfa.
Secondary objectives:
Secondary objectives are to determine the safety and effect of neoGAA treatment on functional endurance (6-minute walk test [6MWT]), inspiratory muscle strength (maximum inspiratory pressure [MIP]), expiratory muscle strength (maximum expiratory pressure [MEP]), lower extremity muscle strength (hand-held dynamometry [HHD]), motor function (Quick Motor Function Test [QMFT]), and health-related quality of life (Short Form-12 [SF-12]). 
Other Objectives:
Additional objectives are to determine the pharmacokinetics (PK), exploratory pharmacodynamics, pharmacogenetics and effect of neoGAA treatment on motor function (Gross Motor Function Measure-88 [GMFM-88] and Gait, Stair, Gower’s Maneuver, and Chair [GSGC]), upper extremity muscle strength (HHD), health-related quality of life (EuroQoL in 5 dimensions [EQ-5D-5L] and Pediatric Quality of Life Inventory [PedsQL] Generic Core Scale), and patient reported outcomes (Pompe Disease Symptom Scale [PDSS], Pompe Disease Impact Scale [PDIS], Rasch-built Pompe-specific Activity scale [R-PAct], and Patient Global Impression of Change [PGIC]).

Inclusion Criteria

1) The patient must provide signed, informed consent prior to performing any study-related procedures. Consent of a legally authorized guardian(s) is (are) required for legally minor patients as defined by local regulation. If the patient is legally minor, signed written consent shall be obtained from parent(s)/legal guardian and assent obtained from patients, if applicable.
2). The patient has confirmed GAA enzyme deficiency from any tissue source and/or 2 confirmed GAA gene mutations.

Exclusion Criteria

E 01. The patient is <3 years of age.
E 02. The patient has known Pompe specific cardiac hypertrophy.
E 03. The patient is wheelchair dependent.
E 04. The patient is not able to ambulate 40 meters (approximately 130 feet) without stopping and without an assistive device. Use of assistive device for community ambulation is appropriate.
E 05. The patient requires invasive-ventilation (non-invasive ventilation is allowed).
E 06. The patient is not able to successfully perform repeated FVC measurements in upright position of ≥30% predicted and ≤85% predicted.
E 07. The patient has had previous treatment with alglucosidase alfa or any investigational therapy for Pompe disease.
E 08. The patient (and patient’s legal guardian if patient is legally minor as defined by local regulation) is (are) not able to comply with the clinical protocol.
E 09. The patient is concurrently participating in another clinical study using investigational treatment or has taken other investigational drugs or prohibited concomitant medications within 30 days or 5 half-lives from screening or randomization, whichever is longer.

E 10. The patient has known history of drug or alcohol abuse within 6 months prior to the time of screening.
E 11. The patient has clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatobiliary, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the study or potentially decreases survival.
E 12. Patient with prior or current use of immune tolerance induction therapy.

Exclusion criteria related to the active comparator and/or mandatory background therapies

Exclusion criteria related to the current knowledge of Sanofi Genzyme compound
E 13. Pregnant or breastfeeding female patient
E 14. Female patient of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy. The patient, if female and of childbearing potential, must have a negative pregnancy test (beta-human chorionic gonadotropin [β-HCG]) at screening/baseline. Pregnancy tests may be performed more frequently in some countries due to local legislations related to female patient of child bearing potential participating in clinical trials. For patients in Sweden, refer to Appendix C. Male participant with a female partner of childbearing potential not protected by highly-effective method(s) of birth control (see Appendix A). For patients in Sweden, refer to Appendix C.
Note: Sexually active female patients of childbearing potential and male patients are required to practice true abstinence in line with their preferred and usual lifestyle or to use two acceptable effective methods of contraception, a barrier method such as a condom or occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository and an established non-barrier method such as oral, injected, or implanted hormonal methods, an intrauterine device, or intrauterine system for the entire duration of the treatment period and for at least 28 days after receiving the last study drug dose. Sterilized or infertile subjects (defined as having undergone surgical sterilization, ie, vasectomy/bilateral tubectomy, hysterectomy and bilateral ovariectomy or as being postmenopausal, defined as at least 12 months of amenorrhea prior to enrollment) will be exempted from the requirements to use contraception in this study (see contraceptive guidance in Appendix A or refer to Appendix C for patients in Sweden).

Additional exclusion criteria during or at the end of screening or run-in phase before randomization
E 15. Patient who has withdrawn consent before enrollment/randomization (starting from signed informed consent form)
E 16. Despite screening of the patient, enrollment/randomization is stopped at the study level

Additional exclusion criteria related to country specific requirements
E 17. Any country-related specific regulation that would prevent the subject from entering the study

Note: FVC% predicted may be repeated three times during the screening period if American Thoracic Society/European Respiratory Society (ATS/ERS) quality criteria have not been met as assessed by the central laboratory. Repeat tests should not occur on the same day in order to allow the patient to rest.

Patients may be re-screened once if their clinical condition changes. Patients who were screen failed because their FVC% predicted was >85% may be re-screened only if a clinically relevant worsening respiratory condition related to Pompe Disease and not related to intercurrent illness assessed by the investigator occurs. Pediatric patients may be re-screened twice if their FVC% predicted was >85%.

In case of rescreening, the patient will be first screened failed in the IXRS, will sign a new written informed consent form and a new patient number will be provided. All screening assessments/procedures will have to be performed again, except GAA and angiotensin converting enzyme (ACE) genotyping.