Proof-of-concept clinical intervention study to analyze whether NRP2945 has anti-epileptic properties in 5 adult participants diagnosed with absence epilepsy
A Phase 2a, single-blind, placebo-controlled safety and efficacy study of two doses of NRP2945 in patients showing drug-resistant typical absence epilepsy as a form of their genetic, generalized epilepsy pattern
CuroNZ Pty Ltd
4 participants
Dec 11, 2018
Interventional
Conditions
Summary
This clinical phase 2 proof-0f-concept study will test the safety and efficacy of NRP2945 in a placebo-controlled fashion within 5 patients diagnosed with drug-resistant absence epilepsy. It is hypothesized that NRP2945 will diminish in quick succession the frequency of drug-resistant absence seizures in patients through the stimulation of inhibitory neural networks in the brain. The formation of inhibitory neural networks are the prerequisite for re-establishing normal neural activity networks in said patients. This potential outcome will be measured through EEG analysis and a potential improvement of quality of life measures will be assessed by questionnaire during the follow-up visit.
Eligibility
Inclusion Criteria11
- Are male or female age 18-65 years.
- Signed informed consent form (ICF) indicating that the subject has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
- Males or non-pregnant, non-breastfeeding females 18 to 65 years-of-age
- Clinical diagnosis of a genetic (idiopathic) generalised epilepsy syndrome (including, but not limited to, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, or Jeavons syndrome) with absence seizures consistent with the International League against Epilepsy Revised Classification of Seizures (2017).
- Absence seizures persisting despite at least two documented standard anti-epileptic treatments (drug-resistance). Subjects are resistant to valproate and at least one other AED (e.g. phenytoin).
- Presence of interictal generalized epileptiform patterns on EEG, including generalized spike-wave or polyspike-wave, generalized polyspike train, generalized paroxysmal fast activity, and generalized low voltage fast activity, within the time frame of 3 hrs of observation period during screening.
- On no therapy or taking stable doses of one or more anti-epileptic medication(s) for at least 30 days. If a subject is not on medication, adequate documentation justifying lack of therapy is acceptable.
- Body Mass Index (BMI) of 18-35 at screening.
- Subjects with reproductive capability including all males and women of child-bearing potential (WOCBP) must agree to practice continuous abstinence or adequate contraception methods (appropriate double barrier method or oral, patch, implant, or injectable contraception) from screening until at least 30 days after the last dose (i.e., intermittent abstinence based on "rhythm", temperature monitoring, or other means of timing is not acceptable).
- Male subjects with a partner of child-bearing potential must be surgically sterilized or be willing to use condoms with spermicide from screening until at least 30 days after the last dose.
- Able and willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion Criteria10
- Have any clinical condition that, in the opinion of the Investigator, might interfere with the results of the study or pose a risk to the subjects due to participation in the study
- Have a history of alcoholism, drug abuse, or drug addiction within the past 12 months.
- Have an active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results.
- Have any clinically significant psychiatric illness, psychological or behavioral problems which, in the opinion of the Investigator, would make the patient unsuitable to participate in the study.
- Have a haemoglobin or haematocrit below the site’s lower reference range value.
- Clinically significant active liver disease, porphyria or have severe hepatic dysfunction indicated by AST and/or ALT greater than 3 x upper limit of normal.
- Currently taking plerixafor® (AMD3100, a highly specific CXCR4 antagonist), or have stopped taking plerixafor® less than 4 weeks before the day of screening.
- Participation in another clinical trial or administration of any investigational agent within 8 weeks or 5 half-lives (whichever is longer) prior to Day 1 or intent to participate in another clinical trial during the study.
- A female who is pregnant or lactating
- An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.
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Interventions
The design is a single-blind, placebo-controlled, sequential dose study in a cross-over design to assess the safety and efficacy of NRP2945 in patients with known stable absence (spike-and-wave discharges) epilepsy. Safety will be assessed by determining the incidence and type of adverse events (AEs), the tolerability of NRP2945 at injection site, and review of clinical laboratory tests and assessments. All intervention treatments, clinical observation periods and analysis will be performed at Royal Melbourne Hospital. Efficacy will be assessed by determining the pharmacodynamics on the cumulative response of the frequency of absence seizures (spike-and-wave discharges) analyzed from the electroencephalogram (EEG) of each subject following the sequential administration of Placebo (Arm 1) and two doses of NRP2945 (5ug/kg and 7ug/kg -- Arm 2 and 3, respectively). The wash-out time in between the three different cohorts is 14 days. The route of administration is subcutaneously and NRp2945 / placebo will be administered as single bolus on day 1 and day 3 of the three treatment regimens, respectively. Subjects will be observed for 8 hrs after each subcutaneous bolus injection and every treatment regimen employs a follow-up visit at 7 days after last dosing. Additional study assessments will include evaluations of concomitant use of anti-epileptic drugs (AED). A questionnaire will be given to subjects at the follow-up visit. The exploratory biomarker CXCR4 (gene expression profiling) will be performed at pre-determined time-points over the course of the study.
Locations(1)
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ACTRN12618001506280