Clinical Program

Marina Biotech’s first therapeutic candidate, CEQ508 for the treatment of Familial Adenomatous Polyposis (FAP), is expected to enter into clinical trials in second half of 2010. CEQ508 will be a first-in-class therapeutic for the treatment of FAP, for which there is no viable pharmaceutical treatment option so that [and for which] surgical intervention is the first-line [primary] treatment approach.

The CEQ508 drug candidate is engineered to enter into dysplastic tissue and release a payload of shRNA, a mediator in the RNAi pathway (see "About RNAi" section). The expressed RNA encodes for the β-catenin gene which is known to be dysregulated in classical FAP. CEQ508 has been shown in the non-clinical setting to reduce the amount of intracellular β-catenin. The clinical trial will be conducted in FAP patients at Massachusetts General Hospital. For more information please contact: clinicaltrials@marinabiotech.com.

Protocol Title:

 A Phase Ia/IIb Open-Label, Escalating-Doses Study, of the Safety and Tolerability of Single Daily Doses of CEQ508, an RNAi-Based Therapy for Familial Adenomatous Polyposis

Sponsor:

 Marina Biotech, Inc.

Study Site:

 MGH, Boston, MA

Principal Investigator:

 Daniel Chung, MD

Projected Start Date:

 Q3 2010

Study Phase:

 CEQ508, a tkRNAi drug candidate (live E.coli carrying RNAi to silence β-catenin)

Objectives:

Primary:

The primary study objective is to evaluate/establish general safety for orally administered CEQ508 in a daily dosing schedule and to determine the Maximum Tolerated Dose (MTD) (of 4 planned doses) and/or the Highest Safest Dose.

Secondary:

  • To examine shedding of CEQ508 in the stool of patients during and after daily oral dosing with CEQ508 for 28 days, and the 28 day recovery period
  • To examine gene expression changes after oral dosing of CEQ508 in GI mucosa of FAP patients

Patient Population:
  • Patients with known FAP and attenuated FAP (AFAP)

Sample Size:
  • Maximum of 30 patients
  • Dose Escalation Phase: 12 patients, at least 4 patients from each sex
  • Stable Dose Phase: 6 patients, who may be newly enrolled or re-enrolled from the 12 patients who were part of the Dose Escalation Phase

Inclusion

Exclusion
  • 18-65 years of age
  • Male and female
  • Clinical or genetic diagnosis of FAP
  • Pre and post colectomy; no immediate need for colectomy
  • Known endoscopic history of polyposis
  • Eligible to undergo baseline and endpoint endoscopies
  • Ability to be taken off other chronic FAP medication (Sulindac, Aspirin, etc.)
  • Informed consent
  • Inability to return for scheduled treatment and assessments
  • Chronic or intercurrent acute medical disorder
  • Significant clinical laboratory and hematology observations
  • Pregnancy, nursing (or anticipated pregnancy)
  • Antibiotic use (current or anticipated antibiotic treatment during the study period; antibiotic use within the past 2 weeks)
  • Active ulcerations or inflammation found at baseline endoscopy
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