Safety Study of Nexvax2 in Subjects With Coeliac Disease

A Phase I Study to Determine Safety, Tolerability and Bioactivity of Nexvax2 in HLA DQ2+ Volunteers With Coeliac Disease Following a Long-term, Strict Gluten-free Diet

The main purpose of this study is to determine the safety of weekly injections of Nexvax2 given for three weeks to patients with coeliac disease who have been on a gluten-free diet.

The second purpose of this study is to compare the immune response over the three week study period in coeliac disease patients given Nexvax2 compared to those given saline.

Study Overview

• Status: Completed
• Conditions: Celiac Disease; Coeliac Disease
• Intervention / Treatment: Other: Placebo; Biological: 9 micrograms Nexvax2; Biological: 30 micrograms Nexvax2; Biological: 90 micrograms Nexvax2; Biological: 60 micrograms Nexvax2; Biological: Up to 900 micrograms Nexvax2

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Q-Pharm Pty Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network - Centre for Clinical Studies

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Age 18 to 60 years (inclusive)

2. Have coeliac disease meeting the following criteria:

   • the Principal Investigator is satisfied coeliac disease has been correctly diagnosed,
   • HLA DQ2 genotype (both HLA DQA1*05 and DQB1*02, homo- or hetero-zygous),
   • no known or suspected gluten exposure for 2 months prior to enrolment
   • were prescribed and have intended to follow a gluten-free diet for at least one year
   • antibodies to tissue transglutaminase (tTG) IgA and/or deamidated gliadin peptide (DGP) IgA and IgG within normal reference range at time of screening.
3. Either male or non-lactating, non-pregnant females who are postmenopausal, sterile or using at least two acceptable and highly effective birth control methods.

Key Exclusion Criteria:

1. Subjects possess the genes encoding HLA DQ8 (either DQA1*03 or DQB1*0302).
2. Uncontrolled complications of coeliac disease which, in the opinion of the Investigator, would impact immune response or pose an increased risk to the subject.
3. Systemic biological agents less than 6 months prior to Day 1.
4. Receipt of systemic immunomodulatory agents or experimental drugs less than 30 days prior to Day 1.

5. Any of the following laboratory abnormalities at Screening:

   • ALT, AST or alkaline phosphatase (ALP) > 1.5 times the upper limit of normal (ULN)
   • Calculated creatinine clearance < 80 mL/min
   • Haemoglobin (Hb) outside of the normal range
   • Platelet count <125 x 109/L
   • Serum potassium outside of the normal range
   • White blood cell (WBC) count outside of the normal range
   • Thyroid stimulating hormone (TSH) outside of the normal range
   • Any other clinically significant abnormal lab values, as determined by the Clinical Investigator.
6. Subjects who smoke or who have smoked at all in the past 3 months.
7. Positive pregnancy test at Screening or Baseline.
8. History of any medically significant condition considered by the Investigator to adversely affect participation in the trial.
9. Non-compliance with a gluten free diet or flare in coeliac disease symptoms from Screening to Baseline.
10. Clinically relevant abnormality on ECGs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline	Other: Placebo; 100 microlitres 0.9% sterile sodium chloride for injection
Experimental: Nexvax2	Biological: 9 micrograms Nexvax2; 9 micrograms, weekly intra-dermal injection, 3 week duration; Biological: 30 micrograms Nexvax2; 30 micrograms, weekly intra-dermal injection, 3 week duration; Biological: 90 micrograms Nexvax2; 90 micrograms, weekly intra-dermal injection, 3 week duration; Biological: 60 micrograms Nexvax2; 60 micrograms, weekly intra-dermal injection, 3 week duration; Biological: Up to 900 micrograms Nexvax2; Up to 900 micrograms, weekly intra-dermal injection, 3 week duration

Collaborators and Investigators

• Sponsor: Nexpep Pty Ltd
• Investigators: Principal Investigator: Gregor Brown, MBBS PhD FRACP, The Alfred Hospital, Victoria; Principal Investigator: James Daveson, MBBS FRACP, Princess Alexandra Hospital, Queensland

Publications and helpful links

General Publications

• Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, van Heel DA, Tatham A, Henderson K, Mannering SI, Gianfrani C, Jewell DP, Hill AV, McCluskey J, Rossjohn J, Anderson RP. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci Transl Med. 2010 Jul 21;2(41):41ra51. doi: 10.1126/scitranslmed.3001012.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: April 8, 2009
• First Submitted That Met QC Criteria: April 9, 2009
• First Posted (Estimate): April 10, 2009

Study Record Updates

• Last Update Posted (Estimate): April 7, 2011
• Last Update Submitted That Met QC Criteria: April 5, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: Nexvax2-001