A randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety and tolerability of Nexvax2 in patients with celiac disease.

Status

Not yet recruiting

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12613001331729

Enrollment

Registered

2013-12-04

Start date

2014-01-13

Completion date

Unknown

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

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

Interventions

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.

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to 70 Years

Healthy volunteers

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)

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.

Outcome results