Clinical trial NCT01427699: A Study of the Safety and Pharmacokinetics of an Anti-Inflammatory Therapeutic Antibody (MABp1) in Patients With Type 2 Diabetes
Official title: A Phase II Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of an Anti-Inflammatory Therapeutic Antibody (MABp1) in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-09-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if T2-18C3, a true human monoclonal antibody that blocks inflammation, is safe to use in patients with type 2 diabetes. The study will also be looking at the ability of T2-18C3 to improve control of blood sugar levels in diabetics by blocking inflammation in the pancreas.

Detailed description: This is a phase I, open label study of the safety and pharmacokinetics of T2-18C3 in patients with T2D. Nine patients will receive four biweekly IV infusions of the study drug, T2-18C3, at a dose level of 1.25 mg/kg. These patients will be followed for a total of 90 days to examine safety, pharmacokinetics, and preliminary efficacy.

Eligibility criteria: Inclusion Criteria:

* American Diabetes Association (ADA) diagnostic criteria for Type 2 Diabetes (T2D)
* HbA1c \>7.0% and ≤ 10%
* Current T2D duration \> 3 months at Screening
* T2D and other diseases must be stable. Stable disease is defined as disease which did not require a change in medication or dosing level on 4 or more consecutive days or 7 days in total within 28 days prior to Day 0.
* Age ≥ 18 and ≤ 70 at Screening
* BMI ≥ 23 and ≤ 40 kg/m2
* For female patients of child-bearing age, a negative serum pregnancy test. For patients with reproductive potential, a willingness to utilize adequate contraception (oral contraception plus a mechanical barrier) and not become pregnant (or have their partner\[s\] become pregnant) during the study
* Agrees not to change diet and exercise regimen during the trial
* Signed and dated Ethics Committee (EC) approved informed consent before any protocol-specific screening procedures are performed

Exclusion Criteria:

* Use of the following medications:

  * Daily use of steroids or aspirin ≥ 700 mg per week
  * Immunosuppressive treatment
  * Thiazolidinediones
  * Concomitant treatment with any other therapeutic antibody, or treatment with any biologic agent that blocks the IL-1 or TNFα signaling pathway
* Change in medication for diabetes within 28 days prior to Day 0, defined as a change in dosing level on 4 or more consecutive days or 7 days in total
* Hemoglobin \<10.0 g/dL, WBC \<3.0 x 103/mm3 , platelet count \<125 x 103/mm3, creatinine \> 1.5mg/dL, AST/ALT \>2 x ULN, alkaline phosphatase \>2 x ULN
* Abnormal, untreated T3, T4, thyroglobulin, or TSH levels or history of Grave's disease
* Known HIV antibody, hepatitis B surface antigen and/or hepatitis C antibody
* History of malignancy within 5 years prior to study entry other than carcinoma in situ of the cervix, or adequately treated, nonmetastatic squamous or basal cell carcinoma of the skin
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
* History of tuberculosis, positive PPD test, active atopic disease requiring medication, or asthma
* Infectious disease:

  * CRP \>30 mg/L, fever, or infection requiring treatment with antibiotics within 3 weeks prior to Screening
  * History of recurrent infection or predisposition to infection
  * Active leg or foot ulcer
* Immunodeficiency
* Female patients who are pregnant, planning to become pregnant during the course of the study, or breast-feeding
* Receipt of a live (attenuated) vaccine within 3 months prior to Screening
* Major surgery within 28 days prior to Day 0
* Participation in an investigational drug or device trial within 30 days prior to Screening

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 90 days
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: 90 days
measure: Preliminary Efficacy
timeFrame: 90 days
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital of Basel
Study officials:
References:
citation: Timper K, Seelig E, Tsakiris DA, Donath MY. Safety, pharmacokinetics, and preliminary efficacy of a specific anti-IL-1alpha therapeutic antibody (MABp1) in patients with type 2 diabetes mellitus. J Diabetes Complications. 2015 Sep-Oct;29(7):955-60. doi: 10.1016/j.jdiacomp.2015.05.019. Epub 2015 Jun 3.