Healthy, Renal Insufficiency
Conditions
Brief summary
This study is being conducted in healthy subjects and in subjects with a mild or moderate decrease in GFR (subjects with renal impairment).
Detailed description
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MGTA-145 in Subjects With Normal Estimated GFR and Varying Degrees of Renal Impairment
Interventions
BIOLOGICALMGTA-145
MGTA-145 will be given intravenously
Sponsors
Ensoma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
for all subjects: 1. Age from 18 to 79 years, inclusive, at the time of signing of the ICF. 2. Body weight ≥50 kg and BMI 19 to 40 kg/m2, inclusive. 3. Systolic blood pressure ≤170 mmHg and diastolic blood pressure ≤100 mmHg at Screening and Day 1. 4. No clinically significant abnormalities on physical examination at Screening. 5. Alanine aminotransferase and aspartate aminotransferase up to 1.5 x the upper limit of normal (ULN) as long as total bilirubin and alkaline phosphatase are ≤ ULN. 6. No clinically significant abnormalities on ECG and QTcF \<480 msec at Screening. 7. Female subjects are not pregnant, non-lactating, and must be of non-childbearing potential being either surgically sterile (eg, documented hysterectomy, bilateral oophorectomy, bilateral salpingo oopherectomy, tubal ligation) or post-menopausal women (over 45 years of age with 12 months or more amenorrhea verified by follicle stimulating hormone assessment and the absence of other biological or physiological causes). 8. Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception (such as condom with spermicide) combined with an acceptable method of contraception for their non-pregnant female partner(s) after informed consent, throughout the study, and for a minimum of 90 days after the last dose, and who do not intend to donate sperm in the period from Screening until 3 months following administration of the study drug. 9. Subject using medications known to affect the elimination of serum creatinine (eg, cimetidine, trimethoprim) within the past 30 days. 10. Capable of providing informed consent and willing to comply with the requirements of the protocol. Specific inclusion criteria for subjects with NORMAL renal function: 11. Estimated GFR (based on MDRD equation) ≥90 mL/min/1.73 m2 (normal) as determined by an average of 2 values obtained at least 48 hours apart within the previous 3 months. 12. White blood cell (WBC) count, hemoglobin and platelet count within normal limits. Absolute neutrophil count of \>1500/µL for African Americans and \>2000/µL for other races. Specific inclusion criteria for subjects with RENAL IMPAIRMENT: 13. Estimated GFR \<90 mL/min/1.73 m2 (based on MDRD equation) as determined by an average of 2 values obtained at least 48 hours apart and within the previous 3 months. 14. Stable renal function as determined by \<20% difference in serum creatinine obtained on 2 occasions at least 48 hours apart and within the previous 3 months. 15. Platelet count ≥100,000/mm3, hemoglobin count ≥10g/dL, WBC count within normal limits. Absolute neutrophil count of \>1500/µL for African Americans and \>2000/µL for other races.
Exclusion criteria
for all subjects: 1. Clinically significant abnormal finding on physical examination conducted at Screening. The assessment may be repeated once prior to treatment number assignment. If the repeat value(s) remains outside of protocol-specified ranges, the subject will be excluded from the study. Note: Re assessment is not allowed for subjects who have a positive urine drug screen test at Screening. 2. History of chronic alcohol or drug abuse within the previous 12 months. Subject has a positive pre-study drug/alcohol screen (to include at minimum: amphetamines, barbiturates, cocaine, opiates, cannabinoids, benzodiazepines, and myelosuppressive drugs). A subject with a positive finding on the drug screen may still be enrolled at the discretion of the Investigator if a plausible clinical explanation exists (eg, prior or concomitant medication use). 3. History of kidney transplantation or requiring dialysis or anticipated to initiate dialysis during the study period. 4. Donation of more than 500 mL of blood or plasma within 12 weeks prior to dosing. 5. Subject smokes more than 10 cigarettes per day (or equivalent) or has done so within 6 months prior to the Screening Visit. 6. Acute illness, infection (requiring medical treatment \[eg, antibiotics\]), or surgery within 30 days of dosing. 7. Seropositive for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus. 8. Subject has received another investigational drug or participated in an investigational device study within 30 days prior to dosing. 9. History of anaphylaxis or clinically important reaction to any drug including plerixafor. Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Biomarkers | 2 days | Investigate area under the curve (AUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 15 days | Investigate the safety and tolerability of MGTA-145 following intravenous (IV) administration as monotherapy in subjects with varying degrees of renal impairment (e.g. adverse events, clinical laboratory tests, vital signs, ECGs) |
Countries
United States
Outcome results
None listed