Safety Study of Ch-mAb7F9 for Methamphetamine Abuse

This study has been completed.
Sponsor:
Collaborators:
University of Arkansas
Information provided by (Responsible Party):
InterveXion Therapeutics, LLC
ClinicalTrials.gov Identifier:
NCT01603147
First received: May 18, 2012
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

The primary objective is to determine the safety and tolerability of single, ascending intravenous doses of ch-mAb7F9 in healthy subjects via physical examinations and adverse event, vital sign, electrocardiogram (ECG), and clinical laboratory testing.Phase 1a, randomized, placebo-controlled, first-in-human (FIH) study of intravenously administered ch-mAb7F9. The study will be a double-blind, dose-escalation study. Each subject will receive a single dose of ch-mAb7F9 or placebo (saline).


Condition Intervention Phase
Methamphetamine Abuse
Biological: normal saline
Biological: ch-mAb7f9
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase Ia, Double-blind, Randomized, Placebo-controlled, Ascending IV Single-dose Study to Evaluate the Safety and Pharmacokinetics of ch mAb7F9 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by InterveXion Therapeutics, LLC:

Primary Outcome Measures:
  • Safety [ Time Frame: 21 weeks ] [ Designated as safety issue: Yes ]
    The primary outcome is to determine the safety and tolerability of single, ascending intravenous doses of ch-mAb7F9 in healthy subjects via physical examinations and adverse event, vital sign, electrocardiogram (ECG), and clinical laboratory testing.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 21 weeks ] [ Designated as safety issue: No ]
    A secondary outcome is to characterize the pharmacokinetics of ch-mAb7F9 following single, ascending intravenous doses of ch-mAb7F9 in healthy subjects by measurement of mAb serum concentrations

  • Immunogenicity [ Time Frame: 21 weeks ] [ Designated as safety issue: No ]
    A secondary outcome is to characterize the immune response following single, ascending intravenous doses of ch-mAb7F9 in healthy subjects by measurement of human anti-ch-mAb7F9 antibody (HACA) serum titers.


Enrollment: 42
Study Start Date: April 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Saline
A total of 10 subjects will receive placebo
Biological: normal saline
saline 225 ml
Experimental: ch-mAb7F9
The single doses to be administered in each cohort are 0.2, 0.6, 2, 6, and 20 mg/kg, respectively.
Biological: ch-mAb7f9
The single doses to be administered in each cohort are 0.2, 0.6, 2, 6, and 20 mg/kg, respectively. Volume to be administered 225 ml

Detailed Description:

There will be 5 dose groups. At the beginning of dosing in each group, 1 subject will receive the normal saline placebo and 1 will receive the active dose. The remainder of the dose group will receive their doses beginning 48 hr later, after safety evaluations. Dosing of the remaining subjects in each dose group will occur 1 at a time, with dosing in each subsequent subject separated by a minimum of 24 hr. Subsequent dose groups will receive their doses beginning approximately 2 weeks after dosing in the preceding group, pending safety analyses.

The single doses to be administered in each cohort are 0.2, 0.6, 2, 6, and 20 mg/kg, respectively. The starting dose will be 0.2 mg/kg, and the highest dose will be 20 mg/kg (up to a maximum of 1,500 mg), which is at least 20-fold lower than the no observable adverse effect level (NOAEL) in rats to ensure subject safety.

Ch-mAb7F9 will be administered intravenously (IV) with a saline flush to clear the administration tubing of residual ch-mAb7F9. Each dose of ch-mAb7F9 will be diluted in 225 ml of saline and given over two hours.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects with the following criteria may be considered for inclusion in the study:

  1. Subject voluntarily agrees to participate in this study and signs an IRB-approved informed consent form prior to performing any of the screening procedures.
  2. Healthy, determined by the PI based on pre-study medical evaluation (medical history and physical examination, vital signs, ECG, and clinical laboratory evaluations).
  3. Males or females between 18 to 50 years of age, inclusive.
  4. The following applies to female subjects:

    - Nonchildbearing potential (surgically sterile [hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/occlusion] or post-menopausal 1 year with follicle stimulating hormone [FSH] > 40 U/L).

    OR

    - Nonpregnant, nonlactating females of childbearing age who agree to use medically acceptable forms of birth control (oral contraceptive pills; contraceptive patches; vaginal ring; diaphragm, sponge, or condom with spermicide; hormone injection; or intrauterine device) from screening to end of study follow-up, or whose partner has had a vasectomy.

  5. The following applies to male subjects:

    • Need to have had a vasectomy or agree to use a condom and spermicide in addition to their female partners using a form of birth control.
    • Agree not to donate sperm for 90 days post dose.
  6. Body mass index (BMI) between 18.5 and 30.5 kg/m2, inclusive, at screening. Body weight ≥ 50 kg and ≤ 100 kg at screening.
  7. Nonsmokers or light smokers (< 10 cigarettes per day) able to refrain from smoking during the in-house period.

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

  1. A history of treatment with a monoclonal antibody in the past year,
  2. likely allergy or sensitivity to ch-mAb7F9 based on known allergies to other mAbs, or which, in the opinion of the Principal Investigator (PI), suggests an increased potential for an adverse hypersensitivity to ch-mAb7F9,
  3. a history of severe allergy (rash, hives, breathing difficulty, etc.) to any medications, either prescription or nonprescription, including dietary supplements or herbal medications,
  4. a history of allergic or environmental bronchial asthma,
  5. a clinically significant history of or current abnormality or disease of any organ system, including renal, hepatic, gastrointestinal, cardiovascular, pulmonary (including chronic asthma), endocrine (eg, diabetes), central nervous, or hematologic systems, or recent clinically significant surgery,
  6. a history of seizure, epilepsy, severe head injury in the opinion of the PI, multiple sclerosis, or other known neurological conditions,
  7. abnormal pre-admission vital signs, physical examination, clinical laboratory, or any safety variable which is considered clinically significant for this population by the PI or Sponsor (or designee), (volunteers who have or are suspected to have Gilbert's syndrome will be discussed on a case by case basis by the PI, Medical Monitor, and Sponsor),
  8. a planned or scheduled surgical procedure during the study,
  9. a clinically significant mental or physical illness within 1 year prior to the first dose, including a history of alcohol and/or drug abuse (DSM IV criteria) within 1 year prior to the first dose of study medication,
  10. any history of stimulant use or abuse, including methamphetamine, amphetamine, or MDMA (ecstasy),
  11. a recent (within 30 days of the first dose of study medication) donation of plasma or blood,
  12. treatment with any medications, either prescription or nonprescription, including dietary supplements or herbal medications, within 14 days prior to the first dose of study medication (exceptions are nonprescription topical medications that are not systemically absorbed, acetaminophen, or vitamins at recommended daily doses),
  13. ingestion of any known hepatic or renal clearance altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazines, St. John's Wort, etc.) within a period of 90 days prior to the first dose of study medication,
  14. ingestion of any approved prescription anti-obesity drug or taken any over-the-counter medication for weight loss within a period of 90 days prior to the first dose of study medication,
  15. ingestion or use of any investigational medication or device within 30 days prior to the first dose of study medication; ingestion or use of any investigational anti-obesity medication is prohibited within 3 months prior to the first dose of study medication,
  16. acute illness within 5 days prior to the first dose of study medication, e.g., flu syndrome, gastrointestinal (GI) virus, or clinically significant indigestion (e.g., reflux) based on the discretion of the PI,
  17. a positive test for HBsAG, Hepatitis C antibody, Hepatitis A IgM, or Human Immunodeficiency Virus (HIV) Viral Serology tests at the screening visit,
  18. a positive urine alcohol test at screening or on Day -1; positive urine drug test for illicit substances (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, tetrahydrocannabinol [THC], phencyclidine, propoxyphene or MDMA) at screening or Day -1.
  19. limited mental capacity to the extent that the subject cannot provide legal consent or understand information regarding the study,
  20. a requirement for a special diet other than vegetarian or has a significant food allergy or intolerance,
  21. any subject judged by the PI or Sponsor (or designee) to be inappropriate for the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01603147

Locations
United States, Kansas
Quintiles Phase 1 Services
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
InterveXion Therapeutics, LLC
University of Arkansas
  More Information

No publications provided

Responsible Party: InterveXion Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT01603147     History of Changes
Other Study ID Numbers: IXT TOA62936, R01DA031944
Study First Received: May 18, 2012
Last Updated: October 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by InterveXion Therapeutics, LLC:
methamphetamine
monoclonal antibody

Additional relevant MeSH terms:
Methamphetamine
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Dopamine Uptake Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014