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Trial registered on ANZCTR


Registration number
ACTRN12613001331729
Ethics application status
Not yet submitted
Date submitted
29/11/2013
Date registered
4/12/2013
Date last updated
4/12/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety and tolerability of Nexvax2 in patients with celiac disease.
Scientific title
A randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety and tolerability of Nexvax2 in patients with celiac disease.
Secondary ID [1] 283652 0
Nil known
Universal Trial Number (UTN)
U1111-1150-7790
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Celiac disease 290602 0
Condition category
Condition code
Inflammatory and Immune System 290990 290990 0 0
Autoimmune diseases
Oral and Gastrointestinal 291022 291022 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nexvax2 is the name of the study drug.

This is a randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety and tolerability of Nexvax2 in patients with celiac disease currently on a Gluten Free Diet.

The study will consist of a 35-day Screening Period (this period will include a double-blind and placebo-controlled gluten challenge lasting 13 of those days), a 15-day Treatment Period, and a 32 day Follow-up Period. Thirteen visits are planned over the 12-week period.

A double-blind and placebo-controlled gluten challenge lasting 13 days will be performed pretreatment (Screening).The 13-day oral challenge is essentially two three-day oral challenges separated by four days and is designed to test the Nexvax2-specific T-cell response following three-day exposure to both active gluten and a gluten placebo.

Three escalating dose treatment cohorts will receive three injections of Nexvax2 60 microgram (Cohort A), 90 microgram (Cohort B), or 150 microgram (Cohort B.1) per dose or placebo (12 patients per cohort) given intradermally on a once weekly schedule in a 2:1 Nexvax2 to placebo ratio. A fourth cohort (Cohort C, “biopsy” cohort) will receive 150 microgram Nexvax2 (14 patients per cohort) given intradermally on a once weekly schedule in a 1:1 Nexvax2 to placebo ratio.

With regards to the Biopsy cohort, the focus of this treatment group is on biopsy histology, this cohort will not undergo either of the 13-day oral challenges. Patients will be seen at Visit 1 (Day -35), Visit 4 (Day -23) and Visit 5 (Day -7) during the Screening Period and at Visit 12 (Day 28) and Visit 13 (Day 47) during the Follow-up Period.
Intervention code [1] 288354 0
Treatment: Drugs
Comparator / control treatment
Placebo- intradermal saline injection
Control group
Placebo

Outcomes
Primary outcome [1] 290989 0
The primary objective of this study is to determine the safety and tolerability of Nexvax2 when administered intradermally to human leukocyte antigen (HLA) DQ2.5+ patients with celiac disease on a Gluten Free Diet.

The objective will be measured via determination of the plasma concentration of Nexvax2 and also through gastrointestinal symptom diary entries by subjects.
Timepoint [1] 290989 0
Treatment period: Weeks 1, 2 and 3 and Follow up period is weeks 3 and 4.

a. Plasma concentration assessed at the following time points: pre-dose, and at 10, 20, 30, and 45 minutes, and 1, 1.5, 2, 4, and 6 hours post dose on Day 1 and Day 15.

B. The diary will be completed daily by the patient beginning at Screening (Day -35) through the End-of Study Visit (Day 47).
Secondary outcome [1] 305760 0
To assess the pharmacokinetics of Nexvax2 when administered intradermally to patients with celiac disease on a GFD.

This outcome is assessed by serum assay and GI symptom diary entry.
Timepoint [1] 305760 0
Weeks 1, 2 and 3 and Follow up period is weeks 3 and 4.

Plasma concentrations will be assessed at these time points: pre-dose, and at 10, 20, 30, and 45 minutes, and 1, 1.5, 2, 4, and 6 hours post dose on Day 1 and Day 15.

The diary will be completed daily by the patient beginning at Screening (Day -35) through the End-of Study Visit (Day 47).
Secondary outcome [2] 305820 0
To assess the effect of Nexvax2 on the immunological response and on clinical tolerance to gluten when administered intradermally to patients with celiac disease on a GFD.

This outcome will be tested by measuring various biomarkers in of inflammatory indicators.
Timepoint [2] 305820 0
Weeks 1, 2 and 3 and Follow up period Weeks 3 and 4.

Samples will be collected on Days 1, 8, 15, 16, 21, 23 and 28.

Eligibility
Key inclusion criteria
1.Patient has signed and understood the informed consent form (ICF) before initiation of any study specific procedures.
2.Patient is between 18 and 70 years old (inclusive).
3.Patient has confirmed “at risk” genotype (HLA-DQ2 and/or DQ8) and has a celiac disease diagnosis consistent with the criteria defined in the National Institutes of Health Consensus Development Conference on Celiac Disease (Department of Health and Human Services, 2004):
*Diagnostic tests should be performed while the patient is on a gluten containing diet.
*A serologic antibody test should be positive.
*Patients with a positive celiac disease antibody test should undergo small bowel biopsy (those with biopsy-proven dermatitis herpetiformis can be excluded from small bowel biopsy).
*Multiple biopsies should be obtained (histologic changes may be focal) and include biopsies from the second portion of the duodenum or beyond.
*Some degree of villous atrophy should be observed.
4.Has HLA DQ2.5 genotype (both DQA1*05 and DQB1*02, homozygous or heterozygous)
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient possesses the genes encoding HLA DQ8 (either DQA1*03 or DQB1*0302).
2. Patient has not been prescribed and/or has not followed a GFD for at least 12 months.
3. Patient has had known gluten exposure within two months prior to Screening.
4. Patient does not have a gluten specific T cell response (measured by IFN-gamma release) following the Screening Period gluten challenge.
5. Patient is female and premenopausal or perimenopausal (< 2 years from last menses) and has a male partner who is not sterile (e.g., not vasectomized, or not having confirmed azoospermia), unless she is sterile (e.g., bilateral tubal ligation with surgery at least 1 month prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 1 month prior to dosing), or unless throughout the entire study period and for 30 days after study drug discontinuation she is using a medically acceptable method of contraception (e.g., abstinence, an intrauterine device, a double-barrier method such as condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, injectable contraceptive, or an oral contraceptive.
6. Patient is male with a premenopausal or perimenopausal (< 2 years from last menses) female partner who is not sterile (as defined in exclusion 5), unless he is sterile (e.g. vasectomized, or having confirmed azoospermia), or unless throughout the entire study period and for 30 days after study drug discontinuation he is using a medically acceptable method of contraception (e.g., abstinence, a double-barrier method such as condom + spermicide or condom + partner using diaphragm with spermicide), or unless his female partner is using a medically acceptable method of contraception (e.g. an intrauterine device, contraceptive implant, injectable contraceptive, or an oral contraceptive).
7. Patient is unable and/or unwilling to comply with study requirements.
8. Patient has had open abdominal surgery within the 12 months or laparoscopic appendectomy or laparoscopic cholecystectomy within 4 months prior to Screening.
9. Patient has a positive test for human immunodeficiency virus (HIV) or active hepatitis B or C disease at the time of Screening.
10. Patient has uncontrolled complications of celiac disease or unstable autoimmune disease which, in the opinion of the investigator, would impact the immune response or pose an increased risk to the patient.
11. Patient has uncontrolled peptic ulcer or gastroesophageal reflux disease or dyspepsia. The patient must be on a stable treatment regimen for their peptic ulcer or gastroesophageal reflux disease for two months prior to Screening.
12. Patient has insulin-dependent diabetes.
13. Patient has had treatment with systemic biological agents (e.g., adalimumab, etanercept, infliximab, certolizumab pegol) less than six months prior to Screening.
14. Patient has taken a nonsteroidal anti-inflammatory drug, systemic antibiotics (oral, IV, IM), or aspirin within the past seven days prior to Screening. Daily low-dose aspirin therapy (up to 100 mg/day) is permitted. Topical antibiotics are permissible.
15. Patient has taken systemic corticosteroids via any route of administration (i.e., oral, IV, IM, intra-articular, or epidural injections) or spironolactone within the previous six weeks prior to Screening. Topical or inhaled (oral for asthma/COPD or nasal for rhinitis/sinusitis) corticosteroids are acceptable.
16. Patient has taken systemic immunomodulatory agents (e.g., azathioprine, methotrexate) less than 60 days prior to Screening.
17. Patient has received an experimental therapy within 30 days prior to Screening.
18. Patient has been previously exposed to Nexvax2.
19. Patient has a history of clinically confirmed allergy and/or anaphylaxis to wheat, barley, or rye.
20. Patient has any of the following laboratory abnormalities at Screening:
*Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than or equal to 2× the upper limit of normal (ULN)
*Hemoglobin less than 10 g/dL
*Platelet count greater than 100 × 109/L
*White blood cell count (WBC) outside the normal range and judged clinically significant by the investigator
*Thyroid-stimulating hormone 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
21. Patient lactating, is known to be pregnant, has a positive pregnancy test at Screening or Day 1 (Baseline), intends to become pregnant, or is nursing.
22. Patient 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.
23. Patient has a history of severe allergic reactions (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that require medical intervention.
24. Patient has donated blood less than or equal to 56 days prior to Screening and plans to donate blood within 5 weeks after study completion.
25. Patient has a clinically relevant abnormality on electrocardiogram (ECG), as determined by the investigator.
26. Patient has inflammatory bowel disease (defined as ulcerative colitis or Crohn’s disease).
27. Other unspecified reasons that in the opinion of the investigator or the sponsor make the patient unsuitable for enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A central randomization schedule will be generated by biostatistics using SAS software (SAS Institute Inc., Cary, North Carolina) Version 9.2. The schedule will be sequestered until the study is unblinded.
There will be two separate randomizations; one for the 13-day oral challenge, and the other for Treatment. Both randomizations will be performed by a central randomization, where the same randomization schedule will be used across all sites, separately for each of the Screening 13 day oral challenge and the study Treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A central randomization schedule will be generated by biostatistics using SAS software (SAS Institute Inc., Cary, North Carolina) Version 9.2. The schedule will be sequestered until the study is unblinded.
There will be two separate randomizations; one for the 13-day oral challenge, and the other for Treatment. Both randomizations will be performed by a central randomization, where the same randomization schedule will be used across all sites, separately for each of the Screening 13 day oral challenge and the study Treatment allocation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA
Recruitment postcode(s) [1] 7590 0
5000 - Adelaide
Recruitment postcode(s) [2] 7591 0
6009 - Nedlands
Recruitment postcode(s) [3] 7592 0
4006 - Herston
Recruitment outside Australia
Country [1] 5656 0
New Zealand
State/province [1] 5656 0
Auckland
Country [2] 5657 0
New Zealand
State/province [2] 5657 0
Christchurch

Funding & Sponsors
Funding source category [1] 288352 0
Commercial sector/Industry
Name [1] 288352 0
ImmusanT
Address [1] 288352 0
One Kendall Square Cambridge, Massachusetts USA 02319
Country [1] 288352 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
ImmusanT
Address
One Kendall Square Cambridge, Massachusetts USA 02319
Country
United States of America
Secondary sponsor category [1] 287060 0
None
Name [1] 287060 0
Address [1] 287060 0
Country [1] 287060 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 290236 0
Bellberry HREC
Ethics committee address [1] 290236 0
129 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 290236 0
Australia
Date submitted for ethics approval [1] 290236 0
30/10/2013
Approval date [1] 290236 0
Ethics approval number [1] 290236 0
2013-11-606

Summary
Brief summary
A Randomized, Double-Blind, Placebo Controlled, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of Nexvax2 in Patients with Celiac Disease.

Primary objective:
*To determine the safety and tolerability of Nexvax2 when administered intradermally to human leukocyte antigen (HLA)-DQ2.5+ patients with celiac disease on a gluten free diet (GFD)
Secondary objectives:
*To assess the pharmacokinetics (PK) of Nexvax2 when administered intradermally to patients with celiac disease on a GFD
*To assess the effect of Nexvax2 on the immunological response and on clinical tolerance to gluten when administered intradermally to patients with celiac disease on a GFD
Exploratory objective:
*To assess the effect of Nexvax2 on small bowel mucosal histology in patients with celiac disease on a GFD
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44538 0
Dr James Daveson
Address 44538 0
QPharm
Level 5 (Clinic and Recruitment & Outpatients)
Clive Berghofer Cancer Research Centre (CBCRC)
300C Herston Road
Herston
QLD 4006
Country 44538 0
Australia
Phone 44538 0
+617 3845 3657
Fax 44538 0
Email 44538 0
jamesdaveson@uq.edu.au
Contact person for public queries
Name 44539 0
Dr James Daveson
Address 44539 0
QPharm
Level 5 (Clinic and Recruitment & Outpatients)
Clive Berghofer Cancer Research Centre (CBCRC)
300C Herston Road
Herston
QLD 4006
Country 44539 0
Australia
Phone 44539 0
+617 3845 3657
Fax 44539 0
Email 44539 0
jamesdaveson@uq.edu.au
Contact person for scientific queries
Name 44540 0
Dr Ferdinand Massari
Address 44540 0
Name: Ferdinand Massari, Chief Medical Officer
Organisation: ImmusanT

One Kendall Square, Cambridge, Massachsetts, USA 02319
Country 44540 0
United States of America
Phone 44540 0
+1 617 299 8399
Fax 44540 0
Email 44540 0
femassari@immusant.com

No information has been provided regarding IPD availability
Summary results
No Results