NOX-A12 Multiple Ascending Dose Study in Healthy Volunteers

NCT01194934 | Completed Phase 1 DMC

• 2 other identifiers: SNOXA12C1012010-020937-14
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is the second clinical study of NOX-A12. This study intends to provide information on the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of repeated intravenous doses of NOX-A12 (2.0 and 4.0 mg/kg/d) alone and to compare the mobilization of hematopoietic stem cells (HSC) obtained with NOX-A12 alone with that obtained in combination with filgrastim in healthy subjects. A single center, open-label, repeated dose study design is selected to best address the study objectives.The results from this study will establish the basis for further development of NOX-A12 in lymphoma patients undergoing autologous hematopoietic stem cell transplantation

Conditions

Hematopoietic Stem Cell Transplantation

Keywords

Stem Cell Transplantation; SDF-1; L-oligonucleotide Aptamer; Spiegelmer; Hematopoietic Stem Cells

Outcome Measures

Primary Outcomes (1)

• To determine the safety and tolerability of repeated doses of NOX-A12 alone and in combination with filgrastim in healthy subjects.

  1 month

Secondary Outcomes (2)

• To determine the pharmacokinetics of repeated doses of NOX-A12 alone and in combination with filgrastim in healthy subjects.

  1 month

• To quantify the mobilization of HSCs in peripheral blood after repeated doses of NOX-A12 alone, of filgrastim alone and after the combination of NOX-A12 with filgrastim.

  1 month

Study Arms (4)

Group A

EXPERIMENTAL

Group A: 2.0 mg/kg NOX-A12 IV every day for 5 days

Drug: NOX-A12

Group B

EXPERIMENTAL

Group B: 4.0 mg/kg NOX-A12 IV every day for 5 days

Drug: NOX-A12

Group C

ACTIVE COMPARATOR

The treatment groups will enter the study sequentially. The decision on starting groups C and D will be made after groups A and B have been completed and data are available. Group C: 5 µg/kg filgrastim SC every day for 5 days

Drug: Filgrastim

Group D

EXPERIMENTAL

The treatment groups will enter the study sequentially. The decision on starting groups C and D will be made after groups A and B have been completed and data are available. Group D: Safe and efficacious dose of NOX-A12 IV in combination with filgrastim SC for 5 days

Drug: NOX-A12 in combination with Filgrastim

Interventions

NOX-A12 DRUG

4 mg/kg daily IV for 5 days

Also known as: olaptesed pegol

Group B

Filgrastim DRUG

5 µg/kg SC daily for 5 days

Also known as: olaptesed pegol

Group C

NOX-A12 in combination with Filgrastim DRUG

Safe and efficacious dose regimen according to results of groups A and B

Also known as: olaptesed pegol

Group D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent signed by the subject.
• Healthy male and female subjects aged 18 to 55 years of any ethnic origin.
• Physically and mentally healthy subjects as confirmed by an interview, medical history, clinical examination, laboratory tests and ECG. Values out of reference range have to be assessed as not clinically significant (NCS) or clinically significant (CS) by the investigator. Individuals presenting deviating values assessed as not clinically significant may be included.
• Male subjects willing to use contraceptive methods from the time of dosing until 3 months after study drug administration (such as condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository), females must be of non-childbearing potential. Non-childbearing potential is defined as follows: Female subjects must be surgically sterile or post-menopausal (defined as at least two years post cessation of menses and follicular stimulating hormone ≥ 35 mIU/mL and serum estradiol ≤25 pg/mL), non-lactating and have a negative pregnancy test.
• Body mass index between 19 and 29 kg/m2 (extremes included).
• Body weight between 50 and 100 kg (extremes included).
• Calculated creatinine clearance ≥ 90 mL/min according to the Cockcroft-Gault-formula.
• Normal lung function (FVC and FEV1 at least 80% of predicted values) at screening.
• O2 saturation between 96% and 100% (extremes included) at screening.
• The subject is co-operative and available for the entire study.

You may not qualify if:

• Evidence in the subject's medical history or in the medical examination of any clinically significant hepatic, renal, gastrointestinal, cardiovascular, pulmonary, hematological or other significant acute or chronic abnormalities which might influence either the safety of the subject or the absorption, distribution, metabolism or excretion of the active agent under investigation.
• History of general malignant diseases.
• History of renal calculus.
• Hypersensitivity to drugs, atopic eczema, allergic bronchial asthma or any clinically significant allergic disease (excluding non-active hayfever).
• Hypersensitivity to the active substances or to any of its excipients.
• Subjects having already received G-CSF in the past.
• Intake of vitamin A derivates or retinoids within 30 days prior to the start of study drug administration.
• Subjects who have a significant history of sensitivity to natural sunlight or artificial light such as ultraviolet (UV) light from sunbeds.
• History of thrombosis or increased bleeding risk.
• Laboratory test results outside the reference values as laid down by the study center, which may be an evidence of disease. Positive result of HIV1/2, HCV antibody or HBs antigen testing.
• Subjects who have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risk of participating in the study, such as QTcB interval \>450 msec (females) and \>430 msec (males), 2nd or 3rd degree atrioventricular block, complete left bundle branch block, complete right bundle branch block or Wolff-Parkinson-White Syndrome, defined as PR\<110 msec, confirmed by a repeated ECG.
• Subjects who have had a clinically significant illness within 8 weeks prior to the start of study drug administration as determined by the investigator.
• History of relevant heart disorders or evidence of hyper- or hypotension (supine blood pressure systolic \>140 mmHg or \<95 mmHg or diastolic \>90 mmHg or \<65 mmHg at screening).
• Bradycardia or bradyarrhythmia (heart rate after 3 minutes supine rest \<45/min at screening).
• Tachycardia or Tachyarrhythmia (heart rate after 3 minutes supine rest \>90/min at screening).

Sponsors & Collaborators

• TME Pharma AG: lead

Study Sites (1)

Charité Research Organisation GmbH

Berlin, Germany

Location

MeSH Terms

Interventions

NOX-A12; Filgrastim

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Frank Fliegert, MD

  TME Pharma AG

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2010
• First Posted: September 3, 2010
• Study Start: August 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: June 26, 2014

Record last verified: 2014-06

Locations

DE (1)