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

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ClinicalTrials.gov Identifier: NCT02679014
Recruitment Status : Completed
First Posted : February 10, 2016
Last Update Posted : August 25, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Celiac Disease Drug: Placebo Drug: RO5459072 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 6, 2016
Actual Primary Completion Date : August 28, 2016
Actual Study Completion Date : August 28, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants will receive placebo capsules (2 capsules) twice daily for 28 days.
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).

Experimental: RO5459072
Participants will receive RO5459072 100 milligrams (mg) capsules (2*50 mg capsules) twice daily for 28 days.
Drug: 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).
Other Name: RG7625




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02679014


Locations
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United Kingdom
Hammersmith Medicines Research Ltd.
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02679014     History of Changes
Other Study ID Numbers: BP29911
2015-002864-18 ( EudraCT Number )
First Posted: February 10, 2016    Key Record Dates
Last Update Posted: August 25, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
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Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases