A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Parallel Study to Investigate the Pharmacokinetics, Pharmacodynamic Effects, Safety and Tolerability of Repeated Dosing of RO5459072 in Volunteers With Celiac Disease

Hoffmann-La Roche1 site in 1 country19 target enrollmentMarch 6, 2016

ConditionsCeliac Disease

InterventionsPlacebo RO5459072

DrugsPlacebo RO5459072

Overview

Phase: Phase 1
Intervention: Placebo
Conditions: Celiac Disease
Sponsor: Hoffmann-La Roche
Enrollment: 19
Locations: 1
Primary Endpoint: Overall Numbers of Participants who are Responders to the Gluten Challenge, Defined as Participants with an Increase in Number of Gliadin Specific T-cells Above Assay-Specific Thresholds
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A randomized, double-blind, placebo-controlled, two treatment, parallel group study to investigate the effects of RO5459072, a cathepsin S inhibitor, on the immune response to a gluten challenge in volunteers with celiac disease. Volunteers with previously diagnosed celiac disease will be randomized to receive either 100 milligrams (mg) RO5459072 or placebo twice daily with food for 28 days (Days 1 to 28).

Registry

clinicaltrials.gov

Start Date

March 6, 2016

End Date

August 28, 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Volunteers with a biopsy confirmed diagnosis of celiac disease
•Human leukocyte antigen (HLA) serotype DQ 2.5 and HLA-DQ 8 haplotypes
•Maintaining a gluten-free diet for at least one year. Compliance will be assessed by serology, compatible responses to a self-reported assessment of gluten-free diet adherence and the absence of typical celiac disease symptoms
•Able to participate and to comply with the study restrictions including the requirements of the gluten challenge

Exclusion Criteria

•A diagnosis of non-celiac gluten sensitivity
•A personal history of food intolerance other than to gluten, or diagnosis of galactosemia, lactose, galactose or fructose intolerance
•A personal history of severe acute symptomatic reaction to sporadic gluten ingestion
•A diagnosis of refractory celiac disease or presence of severe complications of celiac disease
•Diagnosed or suspected immunoglobulin A (IgA) deficiency
•Acute inflammatory bowel disease (ulcerative colitis, Crohn's disease), gastrointestinal obstruction or sub-occlusive syndromes, digestive perforation or risk of digestive perforation, painful abdominal syndromes of undetermined cause
•A history of stomach or intestinal surgery or resection. Appendectomy and hernia repair are acceptable
•Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple allergies (non-active hay fever is acceptable)
•Immunocompromised or with reduced immune function considered to be clinically significant by the Investigator
•Immunization within 30 days before the screening visit or planning vaccination during the study

Arms & Interventions

Placebo

Participants will receive placebo capsules (2 capsules) twice daily for 28 days.

Intervention: Placebo

RO5459072

Participants will receive RO5459072 100 milligrams (mg) capsules (2\*50 mg capsules) twice daily for 28 days.

Intervention: RO5459072

Outcomes

Primary Outcomes

Overall Numbers of Participants who are Responders to the Gluten Challenge, Defined as Participants with an Increase in Number of Gliadin Specific T-cells Above Assay-Specific Thresholds

Time Frame: Day 13 and Day 29

Secondary Outcomes

Percentage of Participants with Adverse Events (AEs)(Up to Day 35)
Number of Participants with an Increase in Antibody Titers (Anti-Tissue Transglutaminase [anti-tTG] Immunoglobulin A [IgA] and Immunoglobulin G [IgG] and Anti-Deamidated Gliadin Peptide (anti-DPG) IgA), as Determined Using Enzyme Immunoassay Methods(Screening, Day 7, Day 13, Day 21, Day 29 and Day 35 (Follow up))
Lactulose to Mannitol Ratio (LMR), Determined by Urine Concentrations of Lactulose and Mannitol(Day 7: 1 hour (hr) pre-dose to 1 hr post-dose, 1 hr to 3 hr post-dose, 3 hr to 5 hr post-dose and Day 21: 1 hr pre-dose to 1 hr post-dose, 1 to 3 hr post-dose, 3 hr to 5 hr post-dose)
Change from Baseline in Number of Circulating White Blood Cells(Day 1 (Baseline), Day 7, Day 13, Day 21, and Day 29)
Change from Baseline in Concentrations of the 10 kilodalton (kDa) Cluster of Differentiation 74 (CD74) Intermediate (Fragment p10) in B Cells(Day 1: pre-dose (=Baseline [BL]) and 4 hours (h) post-dose, Day 7: pre-dose and 4 h post-dose, Day 21: pre-dose and 4 h post-dose)
Change from Baseline in Concentrations of Cathepsin S Mass Biomarker(Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29)
Change from Baseline in Concentrations of Cystatin C Biomarker(Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29)
Maximum Response (Emax ) in p10 upon Cathepsin S Inhibition Ex vivo(Day 1: pre-dose)
Concentration of RO5459072 that Gives Half-maximal Response (EC50) in Ex Vivo p10 Stimulation Assay(Day 1: pre-dose)
Change from Baseline in 4Beta-hydrocholesterol Concentration(Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29)