Intravenous ACP-501 for Familial LCAT Deficiency (rhLCAT)

This primary objective of the study was to use ACP-501 (recombinant LCAT - rhLCAT) as an Expanded Access Protocol in order for one named subject with Familial LCAT Deficiency (FLD) with the hope of slowing or preventing the progression of renal dysfunction and eliminating the need for dialysis. This was a first-in-human study of ACP-501 (rhLCAT) in a subject with FLD. The safety and tolerability of rhLCAT, was assessed after multiple infusions. The pharmacokinetics (PK) of rhLCAT and its effect on the pharmacodynamics (PD) of HDL-C and HDL subpopulations was also be assessed. The duration of the PK and PD parameters will inform future multiple dose studies with respect to dose (mg/kg) and dosing interval. The current protocol completed the primary objection and has shifted to the secondary analysis of samples that were collected. FLD is an extremely rare generic disorders and there are too few subjects to design additional phase 1 trials and these longitudinal samples demonstrating the appearance of normal HDL along with possible biomarkers will be helpful and can help guide the design of a small definitive phase II/II trial.

• INCLUSION CRITERIA:

Subject must meet all of the following inclusion criteria to be eligible for enrollment into the study:

• Greater than or equal to 18 years at screening;
• Confirmed FLD diagnosis through genotype confirmation of a LCAT mutation, as documented at screening or from previous testing;
• History of HDL-C < 15 mg/dL over the past year;
• Serum creatinine > 3 mg/dL;
• Increasing renal dysfunction resulting in ESRD;
• Chronic concomitant medications must be stable for at least 2 weeks prior to screening (for example, lipid-altering drugs and/or ACE-inhibitors used for the treatment of FLD).
• Subject is willing and able to comply with scheduled study visits and is able to tolerate study procedures, including weekly to bi-weekly infusions over 1 year.
• Subject must be able to provide a personally-signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subject may be currently on dialysis or require dialysis during the study

Exclusion criteria

Subject will not be included in the study if he presents with any of the following:

• History of febrile illness within 5 days prior to dosing;
• Active non-basal cell cutaneous malignancy requiring surgery, chemotherapy, and/or radiation in the past 12 months.

NOTE: Subjects with localized prostate cancer under a watchful-waiting treatment plan without evidence of disease progression in the past year may participate in the study if approved by the investigator and sponsor or designee.

NOTE: Subjects diagnosed with basal cell carcinoma of the skin within the past 12 months must receive adequate treatment for their basal cell skin carcinoma prior to randomization.

• Current documented drug or alcohol abuse that would interfere with the subject s compliance with study procedures;
• Treatment with an investigational drug within 28 days prior to dosing.
• Known hypersensitivity to heparin or IV infusion equipment, plastics, adhesive or silicone or known history of hypotension or infusion site reactions with IV administration.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial or compromise the subject s ability to continue with the procedures of the trial.