An interventional study to evaluate the effects of dosages on the Pharmacokinetics (PK, the measure of how the human body processes a substance), Pharmacodynamics (PD, the measure of what a substance does to the human body), Tolerability (how well a substance is tolerated by participants), and Safety of different dosages of IONIS-TMPRSS6-Lrx when given to healthy participants as either a single subcutaneous (SC, an injection just under the skin) dose, or as multiple SC doses.
- Conditions
- ThalassaemiaBlood - Haematological diseases
- Registration Number
- ACTRN12617000458336
- Lead Sponsor
- INCResearch Australia Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 44
1. Must have given written informed consent (signed and dated) and any authorizations
required by local law and be able to comply with all study requirements
2. Healthy males or females of non-childbearing potential, aged 18 to 65 inclusive at the time of informed consent
3. Females must be non-pregnant, non-lactating, non-menstruating (including withdrawal bleeds from hormone replacement therapy in postmenopausal women), and either surgically sterile (by hysterectomy or bilateral oophorectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory involved).
Males must be either abstinent* or, if engaged in sexual relations with a female of childbearing potential, using double methods of contraception that are acceptable from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug.
Males must refrain from sperm donation from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug
*Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception
4. Willing to refrain from strenuous exercise/activity (e.g., heavy lifting, weight training,
intense aerobics classes) for at least 72 hours prior to study visits
5. Body mass index (BMI) < 32 kg
1. Clinically significant abnormalities in medical history (e.g., previous acute coronary
syndrome within 6 months of Screening, major surgery within 3 months of Screening) or
physical examination
2. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion
- Urine protein/creatinine (P/C) ratio greater than or equal to 200 mg/mg. In the event of P/C ratio above this threshold, eligibility may be confirmed by a quantitative total urine protein measurement of < 150 mg/24 hours
- Positive test (including trace) for blood on urinalysis. In the event of a positive test,
eligibility may be confirmed with urine microscopy showing < 5 RBC per microliter
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline
phosphatase, serum creatinine, blood urea nitrogen (BUN) > the upper limit of the normal range (ULN)
- Fasting blood glucose > ULN
- Platelet count < LLN
- Thyroid-stimulating hormone (TSH) value outside normal range unless approved by the Sponsor Medical Monitor
- Hgb < 15.0 g/dL (male) or < 13.0 g/dL (female)
- Any of the following hematologic parameters outside normal range: MCH, MCV, RBC, and RDW
- Ferritin outside normal range
- Transferrin saturation < 20% or > 50%
3. Eligibility of subjects with a known history of anemia must be approved by the Sponsor
Medical Monitor
4. Active infection requiring systemic antiviral or antimicrobial therapy that will not be
completed prior to Study Day 1
5. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
6. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C, or chronic hepatitis B
7. Uncontrolled hypertension (BP > 160/100 mm Hg) at Screening
8. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix that has been successfully treated
9. Treatment with another investigational drug, biological agent, or device within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer
10. Any history of previous treatment with an oligonucleotide (including siRNA). Subjects who have previously received only a single dose of an Ionis oligonucleotide as part of a clinical study may be included as long as a duration greater than or equal to 4 months has elapsed since dosing
11. History of bleeding, diathesis, or coagulopathy
12. Regular excessive use of alcohol within 6 months prior to Screening (> 7 drinks/week for females, > 14 drinks/week for males; 1 drink equals 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor), or use of soft drugs (such as marijuana) within 3 months prior to Screening, or hard drugs (such as cocaine and phencyclidine) within 1 year prior to Screening, or positive urine drug screen at Screening
13. Current use of concomitant medications other than occasional acetaminophen (paracetamol) or ibuprofen unless approved by Sponsor Medical Monitor
14. Use of oral anticoagulants
15. Smoking > 10 cigarettes per day
16. Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 90 days of Screening
17. Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the subject unsui
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method