Clinical trial NCT00453375: Phase 1 Study of BHT-3021 in Subjects With Type 1 Diabetes Mellitus
Official title: A Randomized, Blinded, Placebo Controlled, Safety and Pharmacodynamic Study of BHT-3021 With Open Label Cross-Over in Subjects With Type I Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Hypoglycemia
Keywords: Diabetic
Diabetes
Type 1 Diabetes
Type 1 Diabetes Mellitus
autoimmune disease
Lead sponsor: Bayhill Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-03-28
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety of BHT-3021 injections given weekly for 12 weeks and to evaluate the effect of BHT-3021 on antibody and immune (T cell) responses to autoantigens (e.g. insulin). Changes in pancreatic beta cell function, insulin requirements and blood glucose levels will also be evaluated.

Detailed description: Type 1 diabetes results from an attack by the body's own immune system on the insulin producing cells in the pancreas. Around 80% of diagnosed patients have detectable antibodies to islet cell self-proteins including, insulin IA-2 and glutamic acid decarboxylase. The drug, BHT-3021 is being studied because an agent that stops autoimmune damage could offer patients benefit.

Study Description: A Randomized, Blinded, Placebo Controlled, Safety and Pharmacodynamic Study of BHT-3021 with Open Label Cross-Over in Subjects with Type I Diabetes Mellitus that will enroll up to 72 subjects in this trial. Subjects will be randomized to BHT-3021 or BHT-placebo in a 2:1 ratio.

The duration of the study is approximately 25 to 37 months depending on treatment assignment: 4 week Screening Period; 12 month Blinded Treatment and Evaluation Period; 12 month Cross-over Treatment and Evaluation Period (BHT-placebo subjects only); 12 month Long Term Follow-Up period.

Eligibility criteria: Inclusion Criteria

* Diagnosis of Type 1a Diabetes Mellitus based on ADA Criteria
* ≤5 years since T1D was diagnosed
* ≥ 18 years of age
* ≤ 40 years of age at the time of diagnosis of Type 1a diabetes
* Presence of antibodies to at least one of the following antigens:

insulin, GAD-65, or IA-2

* Detectable fasting C-peptide level
* C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL
* Presence of antibodies to at least one of the following antigens: insulin, GAD-65, or IA-2. If insulin antibody positive only, determination must be within 2 weeks of insulin initiation

Exclusion Criteria:

* BMI \> 30 kg/m2
* Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days
* Current use of inhalable insulin
* Previous immunotherapy for T1D
* Administration of an experimental agent for T1D at any time or use of an experimental device for T1D within 30 days prior to screening, unless approved by the medical monitor
* History of any organ transplant, including islet cell transplant

Primary outcomes:
measure: The primary endpoint in this study is safety.Safety parameters include: stimulated C-peptide response levels, opthalmologic examination, laboratory assessments, 24-hr urine protein, allergic reactions and adverse events including hypoglycemia.
Secondary outcomes:
measure: The secondary endpoints are pharmacodynamic parameters. Parameters include plasmid levels and insulin mRNA levels in blood and urine, Stimulated C-peptide response and Immunological response.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: Fresno
country: United States
facility: Valley Research
state: California
city: Aurora
country: United States
facility: Barbara Davis Center for Childhood Diabetes
state: Colorado
city: Denver
country: United States
facility: Private Practice
state: Colorado
city: Washington
country: United States
facility: MedStar Research Institute
state: District of Columbia
city: Miami
country: United States
facility: University of Miami, Miller School of Medicine, Diabetes Research Institute
state: Florida
city: Wellington
country: United States
facility: Private Practice
state: Florida
city: Omaha
country: United States
facility: Creighton Diabetes Center
state: Nebraska
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Center
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Kippa Ring
country: Australia
facility: Peninsula Clinical Research Centre
state: Queensland
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Ringwood East
country: Australia
facility: Eastern Clinical Research Unit
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Otahuhu
country: New Zealand
facility: Middlemore Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: Canterbury
city: Hamilton
country: New Zealand
facility: Waikato Regional Diabetes Service
state: Waikato
city: Newtown
country: New Zealand
facility: The Diabetes Centre
state: Wellington
Study officials:
affiliation: University of Colorado, Denver
name: Peter Gottlieb, MD
role: STUDY_CHAIR
affiliation: Bayhill Therapeutics Inc.
name: Joanne Quan, MD
role: STUDY_DIRECTOR
affiliation: Walter and Eliza Hall Institute of Medical Research
name: Len Harrison, MD
role: STUDY_CHAIR
References: