An Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of JNJ-17299425 in Participants With Traumatic Brain Injury

Johnson & Johnson (J&J)

Status and phase: Terminated; Phase 2

Conditions: Traumatic Brain Injury

Treatments: Drug: JNJ-17299425

Study type: Interventional

Funder types: Industry

Identifiers

NCT01814982

CR012997

2007-000280-17 (EudraCT Number)

17299425TRM2001

Details and patient eligibility

About

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics (explores what the body does to the drug) and pharmacodynamics (the study of the action or effects a drug has on the body) of JNJ-17299425 in participants with traumatic brain injury (acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem).

Full description

This is an open-label (all people know the identity of the intervention), multi-center (conducted in more than one center), and exploratory study of single and repeat, escalating, intravenous (injection of a substance into a vein) doses of JNJ-17299425 in participants with traumatic brain injury. The study consists of 2 parts (Part 1 and Part 2), and each part will have 2 stages (Stage 1 and Stage 2). In Stage 1 of each part only standard care will be given, through sedation, analgesia and ventilation. If Intra cranial pressure (ICP) rises to greater than 20 millimeter of mercury (mmHG) after ventricular drainage, participants will enter Stage 2 of each part and will receive JNJ-17299425 (single dose in Part 1 and repeated dose in Part 2). During Part 1, safety and efficacy of JNJ-17299425 will be evaluated and during Part 2, safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses will be evaluated. Efficacy will primarily be evaluated by reduction in ICP. Blood samples will be collected for pharmacokinetic evaluation at pre and post administration of study treatment. Participants' safety will be monitored throughout the study.

Enrollment: 7 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with traumatic head injury and requiring intracranial pressure (ICP) monitoring
• Post menopausal females, (or when known not to have menstruated for at least 12 months), or previously documented sterilization
• Body Mass Index (BMI=weight per square height): 18 to 35 kilogram per square meter inclusive
• Legally acceptable representatives (relatives or guardians) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are allowing the participant to participate in the study
• To participate in the optional pharmacogenomic component of this study, legally acceptable representatives (relatives or guardians) must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to consent for this component does not exclude a participant from participation in the clinical study

Exclusion criteria

• Major injury (multi-trauma) or disease outside the central nervous system causing significant vital organ or blood counts dysfunction (for example, disseminated intravascular coagulation, serious hepatic or kidney failure, acute respiratory distress syndrome, etc)
• Participants who already received specific ICP lowering therapy, other than ventricular drainage, before being dosed with JNJ-17299425
• Rapid increase of ICP expected to result in death of the participant
• Relevant abnormal values for hematology, clinical chemistry or urinalysis at admission
• Any known significant history or family history of anemia, hemolytic or autoimmune disease or thrombocytopenia

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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7 participants in 2 patient groups

Part 1: JNJ-17299425

Experimental group

Description:

JNJ-1729425 will be administered once as 1 milligram (10 milliliter of a 0.1 milligram/milliliter (mg/ml) solution) intravenous bolus injection over 2 minutes in central vein. In case of no toxicity or Intra cranial pressure response, dose will be increased to a maximum of 200 milligram (mg).

Treatment:

Drug: JNJ-17299425

Part 2: JNJ-17299425

Experimental group

Description:

JNJ-1729425 will be repeated once at a dose (which is, determined by Investigator in Part 1) as intravenous bolus injection over 2 minutes in central vein.

Treatment:

Drug: JNJ-17299425