A Study to Investigate the Pharmacokinetics, Pharmacodynamic Effects, Safety and Tolerability of Repeated Dosing of RO5459072 in Volunteers With Celiac Disease

Celiac Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02679014
• Other study ID #: BP29911
• Secondary ID: 2015-002864-18
• Status: Completed
• Phase: Phase 1
• First received: February 8, 2016
• Last updated: August 24, 2017
• Start date: March 6, 2016
• Est. completion date: August 28, 2016

Study information

• Verified date: August 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 28, 2016
• Est. primary completion date: August 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

• Women who are pregnant or lactating, or who are of child-bearing potential and do not agree to comply with requirements for contraceptive use. Men who do not agree to comply with requirements for contraceptive use and restrictions on sperm donation

• Participation in an investigational drug or device study within the three months preceding the screening visit

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Drug:
• Placebo
With the exception of the mornings of Days 7 and 21, placebo capsules will be taken orally with a glass of still water in the morning and evening under fed conditions. On the mornings of Days 7 and 21, placebo will be administered under fasted conditions (overnight fast of at least 8 hours before dosing).
• RO5459072
With the exception of the mornings of Days 7 and 21, RO5459072 capsules will be taken orally with a glass of still water in the morning and evening under fed conditions. On the mornings of Days 7 and 21, RO5459072 will be administered under fasted conditions (overnight fast of at least 8 hours before dosing).

Locations

Country	Name	City	State
United Kingdom	Hammersmith Medicines Research Ltd.	London

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Day 13 and Day 29
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to Day 35
Secondary	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)
Secondary	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
Secondary	Change from Baseline in Number of Circulating White Blood Cells		Day 1 (Baseline), Day 7, Day 13, Day 21, and Day 29
Secondary	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
Secondary	Change from Baseline in Concentrations of Cathepsin S Mass Biomarker		Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29
Secondary	Change from Baseline in Concentrations of Cystatin C Biomarker		Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29
Secondary	Maximum Response (Emax ) in p10 upon Cathepsin S Inhibition Ex vivo		Day 1: pre-dose
Secondary	Concentration of RO5459072 that Gives Half-maximal Response (EC50) in Ex Vivo p10 Stimulation Assay		Day 1: pre-dose
Secondary	Change from Baseline in 4Beta-hydrocholesterol Concentration		Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29