A Study to Investigate the Pharmacokinetics, Pharmacodynamic Effects, Safety and Tolerability of Repeated Dosing of RO5459072 in Volunteers With Celiac Disease
Primary Purpose
Celiac Disease
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Placebo
RO5459072
Sponsored by
About this trial
This is an interventional treatment trial for Celiac Disease
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
- 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
Sites / Locations
- Hammersmith Medicines Research Ltd.
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
RO5459072
Arm Description
Participants will receive placebo capsules (2 capsules) twice daily for 28 days.
Participants will receive RO5459072 100 milligrams (mg) capsules (2*50 mg capsules) twice daily for 28 days.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Percentage of Participants with Adverse Events (AEs)
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
Lactulose to Mannitol Ratio (LMR), Determined by Urine Concentrations of Lactulose and Mannitol
Change from Baseline in Number of Circulating White Blood Cells
Change from Baseline in Concentrations of the 10 kilodalton (kDa) Cluster of Differentiation 74 (CD74) Intermediate (Fragment p10) in B Cells
Change from Baseline in Concentrations of Cathepsin S Mass Biomarker
Change from Baseline in Concentrations of Cystatin C Biomarker
Maximum Response (Emax ) in p10 upon Cathepsin S Inhibition Ex vivo
Concentration of RO5459072 that Gives Half-maximal Response (EC50) in Ex Vivo p10 Stimulation Assay
Change from Baseline in 4Beta-hydrocholesterol Concentration
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02679014
Brief Title
A Study to Investigate the Pharmacokinetics, Pharmacodynamic Effects, Safety and Tolerability of Repeated Dosing of RO5459072 in Volunteers With Celiac Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
March 6, 2016 (Actual)
Primary Completion Date
August 28, 2016 (Actual)
Study Completion Date
August 28, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Celiac Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo capsules (2 capsules) twice daily for 28 days.
Arm Title
RO5459072
Arm Type
Experimental
Arm Description
Participants will receive RO5459072 100 milligrams (mg) capsules (2*50 mg capsules) twice daily for 28 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
RO5459072
Other Intervention Name(s)
RG7625
Intervention Description
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).
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Percentage of Participants with Adverse Events (AEs)
Time Frame
Up to Day 35
Title
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)
Title
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
Title
Change from Baseline in Number of Circulating White Blood Cells
Time Frame
Day 1 (Baseline), Day 7, Day 13, Day 21, and Day 29
Title
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
Title
Change from Baseline in Concentrations of Cathepsin S Mass Biomarker
Time Frame
Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29
Title
Change from Baseline in Concentrations of Cystatin C Biomarker
Time Frame
Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29
Title
Maximum Response (Emax ) in p10 upon Cathepsin S Inhibition Ex vivo
Time Frame
Day 1: pre-dose
Title
Concentration of RO5459072 that Gives Half-maximal Response (EC50) in Ex Vivo p10 Stimulation Assay
Time Frame
Day 1: pre-dose
Title
Change from Baseline in 4Beta-hydrocholesterol Concentration
Time Frame
Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Hammersmith Medicines Research Ltd.
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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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