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Completed

NCT Number: NCT02679014

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

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).

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Key information

Conditions

Celiac Disease Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Malabsorption Syndromes Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Hammersmith Medicines Research Ltd.

London, NW10 7EW, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo

Drug

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

Drug

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).

Other names: RG7625

Primary outcomes

  1. 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

  1. Percentage of Participants with Adverse Events (AEs)

    Time frame: Up to Day 35

  2. 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

    Time frame: Screening, Day 7, Day 13, Day 21, Day 29 and Day 35 (Follow up)

  3. Lactulose to Mannitol Ratio (LMR), Determined by Urine Concentrations of Lactulose and Mannitol

    Time frame: 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

  4. Change from Baseline in Number of Circulating White Blood Cells

    Time frame: Day 1 (Baseline), Day 7, Day 13, Day 21, and Day 29

  5. Change from Baseline in Concentrations of the 10 kilodalton (kDa) Cluster of Differentiation 74 (CD74) Intermediate (Fragment p10) in B Cells

    Time frame: 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

  6. Change from Baseline in Concentrations of Cathepsin S Mass Biomarker

    Time frame: Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29

  7. Change from Baseline in Concentrations of Cystatin C Biomarker

    Time frame: Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29

  8. Maximum Response (Emax ) in p10 upon Cathepsin S Inhibition Ex vivo

    Time frame: Day 1: pre-dose

  9. Concentration of RO5459072 that Gives Half-maximal Response (EC50) in Ex Vivo p10 Stimulation Assay

    Time frame: Day 1: pre-dose

  10. Change from Baseline in 4Beta-hydrocholesterol Concentration

    Time frame: Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
Feb 10, 2016
Registry last updated
Aug 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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