Clinical trial NCT00879749: Safety Study of Nexvax2 in Subjects With Coeliac Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coeliac Disease
Celiac Disease
Lead sponsor: Nexpep Pty Ltd
Sponsor class: INDUSTRY
First posted: 2009-04-10
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm Pty Ltd
state: Queensland
city: Melbourne
country: Australia
facility: Nucleus Network - Centre for Clinical Studies
state: Victoria
Study officials:
affiliation: The Alfred Hospital, Victoria
name: Gregor Brown, MBBS PhD FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Alexandra Hospital, Queensland
name: James Daveson, MBBS FRACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.