A Clinical Trial of PR001 (LY3884961) in Patients With Peripheral Manifestations of Gaucher Disease (PROCEED)

This is an interventional treatment trial for Gaucher Disease Read More

Inclusion Criteria:

1. Age 18-50 years inclusive at the time of informed consent.
2. Bi-allelic GBA1 mutations confirmed by the central laboratory.
3. On ERT or SRT for at least 2 years and on a stable, maximum tolerated dose, for at least 3 months prior to screening.

4. Evidence of suboptimal response to ERT or SRT as defined by at least one of the following parameters:

   1. splenomegaly with spleen volume ≥ 3 MN as evaluated by centrally read abdominal MRI
   2. hepatomegaly with liver volume ≥ 1.2 MN as evaluated by centrally read abdominal MRI
   3. thrombocytopenia, with platelet count < 100 × 103 per μL

   4. Bone manifestations of GD of at least moderate severity as defined by at least one of the following:

      • bone crisis within 1 year prior to screening
      • bone marrow infiltration as defined by total BMB score ≥ 7 on MRI
      • severe osteopenia or osteoporosis (Z score < -2.0)
5. Patient has the ability to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
6. Women of nonchildbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle stimulating hormone level in the postmenopausal range.
7. Men and women of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) must use a highly effective method of contraception consistently and correctly for the duration of the study, including the long-term follow-up.
8. Men must agree to use a condom during any sexual intercourse (including those who have had a vasectomy) and abstain from sperm donation for the duration of the study, including long-term follow-up.
9. Women must agree to abstain from egg donation for the duration of the study, including long-term follow-up.
10. Patients must agree to abstain from blood donations for at least the first year of the study.

Exclusion Criteria:

1. Clinically significant neurological signs and symptoms and/or behavioral disturbances.
2. Active and progressive bone disease expected to require surgical treatment in the next 6 months.
3. History of total splenectomy or planned total splenectomy during the first 18 months of the study.
4. Splenomegaly > 10 MN.

5. Evidence of clinically significant liver disease, fragile liver, or history of exposure to hepatotoxins including:

   1. Recipient of a liver transplant or planned liver transplantation during the first 18 months of the study.
   2. Progressive hepatomegaly > 3MN
   3. History of Stage 2 or higher liver fibrosis
   4. History of alcohol or drug abuse within 2 years of Screening
   5. History of hepatitis B (HBV) infection, or currently active HBV infection; patients with a history of hepatitis C virus (HCV) infection must have completed curative antiviral treatment with HCV viral load below the limit of quantification or be HCV RNA negative
6. Thrombocytopenia with platelet count < 40 × 103 per μL.
7. Severe hyperlipidemia (triglycerides > 1,000 mg/dL).
8. Current diagnosis of unstable or clinically significant cardiovascular conditions based on Investigator assessment.
9. History of cancer within 5 years of Screening with the exception of fully excised non-melanoma skin cancers, non-metastatic prostate cancer, and fully treated ductal carcinoma in situ.
10. Concomitant disease, condition or treatment which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
11. Women of childbearing potential, pregnant (i.e., positive serum pregnancy result at Screening and Day 1) or breastfeeding or intending to become pregnant during the course of the trial.
12. Use of any GD-related chaperone therapy within 4 weeks prior to Screening or expected need to initiate chaperone therapy during at least the first 18 months of the study.
13. Any type of prior gene or cell therapy.
14. Use of systemic immunosuppressant or steroid therapy other than protocol-specified immunosuppression.
15. Participation in another therapeutic investigational drug or device study within 3 months or 5 half-lives of the study agent, whichever is longer.
16. Clinically significant abnormalities in laboratory test results at Screening.