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Safety and Tolerability of Nexvax2 in Subjects With Celiac Disease

Primary Purpose

Celiac Disease

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Nexvax2
Nexvax2 placebo
Sponsored by
ImmusanT, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Celiac Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subject has signed and understands the informed consent form before initiation of any study specific procedures.
  2. Subject is between 18 and 70 years old (inclusive) on the date of the Screening Visit.
  3. Subject has been diagnosed with celiac disease on the basis of intestinal histology showing villous atrophy according to expert guidelines current at the time of diagnosis.
  4. Subject has HLA DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02).

Exclusion Criteria:

  1. Subject has not been maintained on a gluten-free diet for at least 1 year.
  2. Celiac Dietary Adherence Test at screening indicates non-compliance to gluten-free diet (score >12).
  3. Serum levels of both recombinant human transglutaminase (tTG)-specific immunoglobulin-A (IgA) and deamidated gliadin peptide (DGP)-specific immunoglobulin-G (IgG) are elevated above the manufacturer's upper limit of normal. The elevation of one or other of the serology test for tTG IgA and DGP IgG is not an exclusion.
  4. Subject has uncontrolled complications of celiac disease or a medical condition which, in the opinion of the investigator, would impact the immune response or pose an increased risk to the subject.
  5. Subject is or has been using an immuno-modulatory or immune suppressing medical treatment during the 2 months prior to Screening, for example azathioprine, methotrexate, or biological
  6. Subject is female and premenopausal or perimenopausal and has a male partner who is not sterile, unless she is sterile, or she practices true abstinence, or unless throughout the entire study period and for 30 days after study drug discontinuation she is using a medically acceptable method of contraception.
  7. Subject is male with a premenopausal or perimenopausal female partner who is not sterile, unless he is sterile, or he practices true abstinence, or unless throughout the entire study period and for 30 days after study drug discontinuation he is using a medically acceptable method of contraception, or unless his female partner is using a medically acceptable method of contraception.
  8. Subject is unable and/or unwilling to comply with study requirements.
  9. Subject has taken oral or parenteral corticosteroids within the previous six weeks prior to Screening. Topical or inhaled corticosteroids are acceptable.
  10. Subject has received an experimental therapy within 30 days prior to Screening.
  11. Subject has previously been enrolled and dosed in a clinical trial with Nevax2.
  12. Subject has any of the following laboratory abnormalities at Screening:

    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) ≥ 2 × the upper limit of normal (ULN)
    • Hemoglobin <10 g/dL
    • Platelet count <100 × 109/L
    • White blood cell count (WBC) outside the normal range and judged clinically significant by the investigator
    • Direct bilirubin outside the normal range
    • Any other clinically significant abnormal laboratory values, as determined by the investigator
  13. Subject is lactating, is known to be pregnant, has a positive pregnancy test at Screening or Treatment Day, intends to become pregnant, or is nursing.
  14. Subject has a history or presence of any medically significant condition considered by the investigator to have the potential to adversely affect participation in the study and/or interpretation of the study results.
  15. Subject has a history of severe allergic reactions (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that require medical intervention.
  16. Subject has donated blood ≤ 56 days prior to Screening and plans to donate blood within 5 weeks after study completion.
  17. Subject has a clinically relevant abnormality on electrocardiogram (ECG), as determined by the investigator.
  18. Other unspecified reasons that in the opinion of the investigator or the sponsor make the subject unsuitable for enrollment.

Sites / Locations

  • Q-Pharm Pty Ltd.
  • CMAX, A Division of IDT Australia Ltd
  • Linear Clinical Research
  • Auckland Clinical Studies Ltd

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Nexvax2 DQ2.5 Homozygotes (Cohort 1)

Nexvax2 Placebo DQ2.5 Homozygotes (Cohort 1)

Nexvax2 DQ2.5 Non-homozygotes (Cohort 2)

Nexvax2 Placebo DQ2.5 Non-homozygotes (Cohort 2)

Nexvax2 DQ2.5 Non-homozygotes (Cohort 3)

Nexvax2 Placebo DQ2.5 Non-homozygotes (Cohort 3)

Arm Description

Nexvax2 by ID injections for a total of 14 doses over 46 days.

Nexvax2 Placebo by ID injections for a total of 14 doses over 46 days.

Nexvax2 by ID injections for a total of 14 doses over 46 days.

Nexvax2 Placebo by ID injections for a total of 14 doses over 46 days.

Nexvax2 by ID injections for 18 doses (up to 27 doses) over 60 days (maximum of 91 days).

Nexvax2 Placebo by ID injections for 18 doses (up to 27 doses) over 60 days (maximum of 91 days).

Outcomes

Primary Outcome Measures

Incidence of toxicity and safety of Nexvax2 according to the "Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0"
Number and Percentage of Participants with Treatment-related Adverse Events assessed by the "Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 will be tabulated using counts and proportions detailing frequently occurring, serious and severe events. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to study treatments.

Secondary Outcome Measures

Weekly Gastrointestinal Symptom Rating Scale (GSRS)
The GSRS score is the average weekly scores for 15 symptoms rated on a 7-point severity scale. GSRS scores over the 6-week Treatment Period will be compared.
Plasma Cytokine Levels
The relative change from pre-dose levels up to 10 hours after dosing in the concentration of plasma cytokines.

Full Information

First Posted
August 17, 2015
Last Updated
December 20, 2018
Sponsor
ImmusanT, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02528799
Brief Title
Safety and Tolerability of Nexvax2 in Subjects With Celiac Disease
Official Title
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Nexvax2 Preceded by a Dose Titration Period in Subjects With Celiac Disease Currently on a Gluten-Free Diet
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
January 6, 2017 (Actual)
Study Completion Date
January 6, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ImmusanT, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A randomized, double-blind, placebo-controlled, dose titration trial, stratified by Human Leukocyte Antigen (HLA)-DQ2.5 genotype in subjects with celiac disease.
Detailed Description
This is a randomized, double-blind, placebo-controlled, study to evaluate the safety and tolerability of Nexvax2 preceded by dose titration period in patients with celiac disease currently on a gluten-free diet. The study will consist of a Screening Period, a Treatment Period, and a Follow-up Period. Eligible subjects will be enrolled in one of three cohorts according to whether they are homozygous or not homozygous for both genes coding for HLA-DQ2.5.

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
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nexvax2 DQ2.5 Homozygotes (Cohort 1)
Arm Type
Experimental
Arm Description
Nexvax2 by ID injections for a total of 14 doses over 46 days.
Arm Title
Nexvax2 Placebo DQ2.5 Homozygotes (Cohort 1)
Arm Type
Placebo Comparator
Arm Description
Nexvax2 Placebo by ID injections for a total of 14 doses over 46 days.
Arm Title
Nexvax2 DQ2.5 Non-homozygotes (Cohort 2)
Arm Type
Experimental
Arm Description
Nexvax2 by ID injections for a total of 14 doses over 46 days.
Arm Title
Nexvax2 Placebo DQ2.5 Non-homozygotes (Cohort 2)
Arm Type
Placebo Comparator
Arm Description
Nexvax2 Placebo by ID injections for a total of 14 doses over 46 days.
Arm Title
Nexvax2 DQ2.5 Non-homozygotes (Cohort 3)
Arm Type
Experimental
Arm Description
Nexvax2 by ID injections for 18 doses (up to 27 doses) over 60 days (maximum of 91 days).
Arm Title
Nexvax2 Placebo DQ2.5 Non-homozygotes (Cohort 3)
Arm Type
Placebo Comparator
Arm Description
Nexvax2 Placebo by ID injections for 18 doses (up to 27 doses) over 60 days (maximum of 91 days).
Intervention Type
Biological
Intervention Name(s)
Nexvax2
Intervention Description
Nexvax2 intra-dermal injections twice weekly
Intervention Type
Biological
Intervention Name(s)
Nexvax2 placebo
Intervention Description
Sodium chloride 0.9% intra-dermal injections twice weekly
Primary Outcome Measure Information:
Title
Incidence of toxicity and safety of Nexvax2 according to the "Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0"
Description
Number and Percentage of Participants with Treatment-related Adverse Events assessed by the "Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 will be tabulated using counts and proportions detailing frequently occurring, serious and severe events. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to study treatments.
Time Frame
Treatment Period (~7 to 9 weeks)
Secondary Outcome Measure Information:
Title
Weekly Gastrointestinal Symptom Rating Scale (GSRS)
Description
The GSRS score is the average weekly scores for 15 symptoms rated on a 7-point severity scale. GSRS scores over the 6-week Treatment Period will be compared.
Time Frame
Treatment Period (~7 to 9 weeks)
Title
Plasma Cytokine Levels
Description
The relative change from pre-dose levels up to 10 hours after dosing in the concentration of plasma cytokines.
Time Frame
Treatment Period (~7 to 9 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject has signed and understands the informed consent form before initiation of any study specific procedures. Subject is between 18 and 70 years old (inclusive) on the date of the Screening Visit. Subject has been diagnosed with celiac disease on the basis of intestinal histology showing villous atrophy according to expert guidelines current at the time of diagnosis. Subject has HLA DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02). Exclusion Criteria: Subject has not been maintained on a gluten-free diet for at least 1 year. Celiac Dietary Adherence Test at screening indicates non-compliance to gluten-free diet (score >12). Serum levels of both recombinant human transglutaminase (tTG)-specific immunoglobulin-A (IgA) and deamidated gliadin peptide (DGP)-specific immunoglobulin-G (IgG) are elevated above the manufacturer's upper limit of normal. The elevation of one or other of the serology test for tTG IgA and DGP IgG is not an exclusion. Subject has uncontrolled complications of celiac disease or a medical condition which, in the opinion of the investigator, would impact the immune response or pose an increased risk to the subject. Subject is or has been using an immuno-modulatory or immune suppressing medical treatment during the 2 months prior to Screening, for example azathioprine, methotrexate, or biological Subject is female and premenopausal or perimenopausal and has a male partner who is not sterile, unless she is sterile, or she practices true abstinence, or unless throughout the entire study period and for 30 days after study drug discontinuation she is using a medically acceptable method of contraception. Subject is male with a premenopausal or perimenopausal female partner who is not sterile, unless he is sterile, or he practices true abstinence, or unless throughout the entire study period and for 30 days after study drug discontinuation he is using a medically acceptable method of contraception, or unless his female partner is using a medically acceptable method of contraception. Subject is unable and/or unwilling to comply with study requirements. Subject has taken oral or parenteral corticosteroids within the previous six weeks prior to Screening. Topical or inhaled corticosteroids are acceptable. Subject has received an experimental therapy within 30 days prior to Screening. Subject has previously been enrolled and dosed in a clinical trial with Nevax2. Subject has any of the following laboratory abnormalities at Screening: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) ≥ 2 × the upper limit of normal (ULN) Hemoglobin <10 g/dL Platelet count <100 × 109/L White blood cell count (WBC) outside the normal range and judged clinically significant by the investigator Direct bilirubin outside the normal range Any other clinically significant abnormal laboratory values, as determined by the investigator Subject is lactating, is known to be pregnant, has a positive pregnancy test at Screening or Treatment Day, intends to become pregnant, or is nursing. Subject has a history or presence of any medically significant condition considered by the investigator to have the potential to adversely affect participation in the study and/or interpretation of the study results. Subject has a history of severe allergic reactions (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that require medical intervention. Subject has donated blood ≤ 56 days prior to Screening and plans to donate blood within 5 weeks after study completion. Subject has a clinically relevant abnormality on electrocardiogram (ECG), as determined by the investigator. Other unspecified reasons that in the opinion of the investigator or the sponsor make the subject unsuitable for enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert P. Anderson, MB ChB, PhD
Organizational Affiliation
ImmusanT, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Q-Pharm Pty Ltd.
City
Herston
State/Province
Queensland
ZIP/Postal Code
4006
Country
Australia
Facility Name
CMAX, A Division of IDT Australia Ltd
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Linear Clinical Research
City
Nedlands
ZIP/Postal Code
WA 6009
Country
Australia
Facility Name
Auckland Clinical Studies Ltd
City
Auckland
ZIP/Postal Code
1150
Country
New Zealand

12. IPD Sharing Statement

Citations:
PubMed Identifier
29191561
Citation
Daveson AJM, Ee HC, Andrews JM, King T, Goldstein KE, Dzuris JL, MacDougall JA, Williams LJ, Treohan A, Cooreman MP, Anderson RP. Epitope-Specific Immunotherapy Targeting CD4-Positive T Cells in Celiac Disease: Safety, Pharmacokinetics, and Effects on Intestinal Histology and Plasma Cytokines with Escalating Dose Regimens of Nexvax2 in a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study. EBioMedicine. 2017 Dec;26:78-90. doi: 10.1016/j.ebiom.2017.11.018. Epub 2017 Nov 22.
Results Reference
derived
Links:
URL
http://www.nlm.nih.gov/medlineplus/
Description
MedlinePlus

Learn more about this trial

Safety and Tolerability of Nexvax2 in Subjects With Celiac Disease

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