Safety and Tolerability of HemaMax™ (rHuIL-12) as Radiation Countermeasure

• ClinicalTrials.gov Identifier: NCT01742221
• Recruitment Status: Completed
• First Posted: December 5, 2012
• Last Update Posted: November 16, 2018
• Sponsor: Neumedicines Inc.
• Collaborator: Department of Health and Human Services
• Information provided by (Responsible Party): Neumedicines Inc.

Study Description

Brief Summary:

This trial is designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of HemaMax in healthy male and female volunteers.

Condition or disease	Intervention/treatment	Phase
Hematopoietic Syndrome Due to Acute Radiation Syndrome	Biological: HemaMax; Drug: Placebo	Phase 1

Detailed Description:

A randomized, placebo-controlled, double-blind study of HemaMax to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of a single 12 μg subcutaneous dose of HemaMax on 60 healthy subjects for 28 days after HemaMax administration.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1b, Single-Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HemaMax™ (rHuIL-12) in Healthy Subjects
• Study Start Date: August 2012
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: HemaMax; Single subcutaneous 12 microgram dose of HemaMax	Biological: HemaMax; single subcutaneous 12 microgram dose of HemaMax; Other Name: rHuIL-12, NM-IL-12
Placebo Comparator: Placebo; Single subcutaneous dose	Drug: Placebo; single subcutaneous dose

Outcome Measures

Primary Outcome Measures :

1. To determine the safety and tolerability of HemaMax in healthy subjects. [ Time Frame: 3 months ]
   Number of subjects with adverse events as a measure of safety and tolerability

Secondary Outcome Measures :

1. To characterize the pharmacokinetics, pharmacodynamics and immunogenicity of HemaMax in healthy subjects [ Time Frame: 3 months ]
   To evaluate PK parameters AUC, Cmax, Tmax, t ½, Vz/F, and CL/F for HemaMax. To evaluate biological response parameters following HemaMax.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

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

  1. 18 to 45 years of age
  2. Body mass index (BMI) > 19 and < 0 kg/m2
  3. Normal ECG, vital signs and laboratory test results
  4. Use of effective birth control method and abstinence from sex
  5. Negative pregnancy test and drug screen

Exclusion Criteria:

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

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

Contacts and Locations

Locations

United States, Wisconsin

Covance Clinical Research Unit

Madison, Wisconsin, United States, 53704

Sponsors and Collaborators

Neumedicines Inc.

Department of Health and Human Services

Investigators

• Principal Investigator: Nicholas Siebers, MD; Covance Clinical Research Unit

More Information

Publications:

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.

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. Epub 2015 Jul 24.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Neumedicines Inc.
• ClinicalTrials.gov Identifier: NCT01742221
• Other Study ID Numbers: 2012-002
• First Posted: December 5, 2012
• Last Update Posted: November 16, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Neumedicines Inc.:

HemaMax, NM-IL-12, HSARS, Safety

Additional relevant MeSH terms:

Radiation Injuries; Acute Radiation Syndrome; Wounds and Injuries