Clinical trial NCT02343133: Safety Study of HemaMax™ (rHuIL-12) to Treat Acute Radiation Syndrome
Official title: A Phase 2 Single-Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HemaMax™ (rHuIL-12) in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematopoietic Syndrome Due to Acute Radiation Syndrome
Keywords: HemaMax, NM-IL-12, HSARS, Safety
Lead sponsor: Neumedicines Inc.
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2015-01-21
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether HemaMax is safe and well tolerated to support efficacy under FDA's Animal Rule to reduce the morbidity and mortality associated with the hematopoietic syndrome of acute radiation syndrome.

Detailed description: This is a phase 2 single dose, randomized, double-blind, placebo-controlled, multi center study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HemaMax™ (rHuIL-12) in healthy adult male and female subjects considered representative of U.S. population.

Eligibility criteria: Inclusion Criteria:

Male and Female healthy subjects who have signed the informed consent form must meet all of the following criteria

* ≥18 to ≤75 years of age
* Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2
* Normal ECG, vital signs and laboratory test results
* Use of effective birth control method and abstinence from sex
* Negative pregnancy test and drug screen

Exclusion Criteria:

Subjects with any of the following characteristics will be considered ineligible:

* History of clinically significant renal, hepatic pulmonary, cardiovascular, cerebrovascular, gastrointestinal, metabolic, hematological, endocrine, urological, immunological, neurologic or psychiatric disorders or connective tissue disease
* Positive for human immunodeficiency virus (HIV), Hepatitis B, or surface antigen (HBsAg) or Hepatitis C antibody, tuberculosis (TB)
* Drug or alcohol addiction
* History of clinically significant allergy of any kind
* Prior use of IL-12 or HemaMax
* Use of any approved or investigational biologic agents or vaccinations of any kind in last 3 months

Primary outcomes:
measure: Safety and tolerability of HemaMax (Number of subjects with adverse events as a measure of safety and tolerability)
timeFrame: 3 months
Secondary outcomes:
measure: Pharmacokinetics of HemaMax (AUC, Cmax and Tmax)
timeFrame: 3 months
measure: Pharmacodynamics of HemaMax (IFN-g and CXCL-10 induction as a measure of pharmacodynamic response)
timeFrame: 3 months
measure: Immunogenicity of HemaMax (Anti-drug antibodies as a measure of immunogenicity)
timeFrame: 3 months
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit
state: Florida
city: Evansville
country: United States
facility: Covance Clinical Research Unit
state: Indiana
city: Dallas
country: United States
facility: Covance Clinical Research Unit
state: Texas
city: Madison
country: United States
facility: Covance Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Covance Clinical Research
name: Nicholas Siebers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gokhale MS, Vainstein V, Tom J, Thomas S, Lawrence CE, Gluzman-Poltorak Z, Siebers N, Basile LA. Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects. Exp Hematol Oncol. 2014 Apr 11;3(1):11. doi: 10.1186/2162-3619-3-11.
citation: Gluzman-Poltorak Z, Vainstein V, Basile LA. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure. Am J Hematol. 2014 Sep;89(9):868-73. doi: 10.1002/ajh.23770. Epub 2014 Jun 19.
citation: Gluzman-Poltorak Z, Vainstein V, Basile LA. Association of Hematological Nadirs and Survival in a Nonhuman Primate Model of Hematopoietic Syndrome of Acute Radiation Syndrome. Radiat Res. 2015 Aug;184(2):226-30. doi: 10.1667/rr13962.1. Epub 2015 Jul 24.
citation: Gluzman-Poltorak Z, Mendonca SR, Vainstein V, Kha H, Basile LA. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation. J Hematol Oncol. 2014 Apr 6;7:31. doi: 10.1186/1756-8722-7-31.
citation: Basile LA, Ellefson D, Gluzman-Poltorak Z, Junes-Gill K, Mar V, Mendonca S, Miller JD, Tom J, Trinh A, Gallaher TK. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates. PLoS One. 2012;7(2):e30434. doi: 10.1371/journal.pone.0030434. Epub 2012 Feb 24.