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.

A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-TMPRSS6-Lrx Administered Subcutaneously to Healthy Volunteers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12617000458336

Enrollment

Registered

2017-03-30

Start date

2017-06-08

Completion date

2018-06-26

Last updated

2020-12-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This research project is being conducted to look at the safety, tolerability, pharmacokinetics (PK, how the human body processes a substance) and pharmacodynamics (PD, the measure of what a substance does to the human body), 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 over a course of 6 weeks.

Interventions

Cohort A: 20mg IONIS-TMPRSS6-Lrx/ placebo as 0.2mL SC injection on Days 1, 22, 25, 29, 36, 43, 50, and 57, for a total dosage of 160mg IONIS-TMPRSS6-Lrx or placebo. Cohort B: 40mg IONIS-TMPRSS6-Lrx/ placebo as 0.4mL SC injection on Days 1, 22, 25, 29, 36, 43, 50, and 57, for a total dosage of 320mg IONIS-TMPRSS6-Lrx or placebo. Cohort C: 60mg IONIS-TMPRSS6-Lrx/ placebo as 0.6mL SC injection on Days 1, 22, 25, 29, 36, 43, 50, and 57, for a total dosage of 480mg IONIS-TMPRSS6-Lrx or placebo. Cohor

Study design

Allocation

Randomised controlled trial

Intervention model

Other

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

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

Exclusion criteria

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 unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Outcome results