A Single-dose, Dose-escalation Study of a Long-acting MOD-5014 in Healthy Adult Male

Study Overview
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Brief Summary
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A Phase 1, randomized, single-blind, placebo-controlled, single dose, dose-escalation study to assess the safety, pharmacokinetic and pharmacodynamic profile of subcutaneous administration of a long-acting recombinant factor VIIa (MOD-5014) in healthy adult males.

Detailed Description
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This will be a single-dose, randomized, single-blind, placebo-controlled, dose-escalating study. The study will include four escalating dose groups, with eight subjects in each dose group. Subjects will be randomized in 3:1 ratio to receive a single SC injection of MOD-5014 (n=6) or a placebo (n=2), and will be followed up for 30 days. The initial MOD-5014 dose group will receive 100 µg/kg followed by single doses of 200, 400 and 600 µg/kg administered to subsequent subject cohorts. The decision to proceed to the higher dose level will be made by a Data Safety Monitoring Board (DSMB) after review of relevant safety data (including adverse events, clinical laboratory and vital signs), collected up to and including 7 days after the last subject of the previous dose group has been dosed. Common Terminology Criteria for Adverse Events (CTCAE) guidelines will be used to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT). Dose escalation will be permitted if the prior dose is well tolerated, and there are no safety or tolerability concerns raised by the investigator, sponsor, medical monitor or DSMB over 7 days post-dosing.

Official Title
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A Phase 1,Randomized, Single-blind, Placebo-controlled, Single Dose, Dose-escalated Study to Assess the Safety, Pharmacokinetic and Pharmacodynamic Profile of Subcutaneous Administration of a Long-acting Recombinant Factor VIIa in Healthy Adult Males

Conditions
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Hemophilia A or B With Inhibitors

Intervention / Treatment
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* Biological: MOD-5014
* Other: MOD-5014 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men, 18-50 years of age, inclusive, at the screening visit. Subjects must provide written informed consent prior to participating in the study. Considered healthy based on medical history, physical examination and clinical laboratory results. Body Mass Index (BMI) 19.0-30.0 kg/m2 and total body weight >50 Kg. Fertile men must agree to use a barrier contraceptive (condom) for 30 days post-dosing and are restricted from donating sperm for 30 days after dosing. Subjects with a vasectomy performed more than 6 months prior to treatment are also acceptable. Supine blood pressure and heart rate within normal limits (systolic 90-140 mmHg; diastolic 50-90 mmHg, heart rate 45-100 beats per minute). No evidence of orthostatic hypotension. Triglyceride ≤ 200 mg/dl ECG with no clinically significant abnormalities recorded at Screening visit and on dosing day (before drug administration): PR interval within 120 and 210 ms, QRS interval < 120 ms, and QTc interval 450 ms. Negative human immunodeficiency virus (HIV), hepatitis B or hepatitis C serology tests at screening. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Non-smoking and no use of any tobacco or nicotine product by declaration for a period for at least 6 month prior to screening period. Exclusion Criteria: Family history of blood clots. Have had, within one month prior to study drug administration, a major surgical procedure (e.g. orthopedic, abdominal) or have an elective surgery planned within the study period. Any history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism). History or current drug/alcohol abuse (excluding use of medicinal cannabis for pain management). History of regular alcohol consumption exceeding - 14 drinks/week for men (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of screening. Positive urine drug of abuse (DoA) in screening and on admission. Positive breath alcohol test on admission. Known allergy to any drug. Known allergy or hypersensitivity to any of the test compounds or materials or contraindication to test product. Use of any prescription or over-the-counter (OTC) medications, including vitamins and herbal or dietary supplements within 14 days prior to dosing. Paracetamol for symptomatic relief of pain is allowed until 24 hours prior to the study drug administration. Subjects who have received any vaccines within 4 weeks prior to study drug administration. Participation in another clinical trial within 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOD-5014<br>MOD-5014 longevity is the result of fusion of three consecutive C-terminal peptide (CTP) domains to the C-terminus of FVII. CTP technology is based on a natural peptide, the C-terminal peptide of the beta chain of human chorionic gonadotropin (hCG), which provides hCG with the required longevity to maintain pregnancy (initial half-life [t1/2]  10 h, terminal t1/2  37 h). The beta chain of luteinizing hormone (LH), a gonadotropin that triggers ovulation, is almost identical to hCG but does not include the CTP. As a result, LH has a significantly shorter half-life in blood (initial t1/2  1 h, terminal t1/2  10 h) (Fares et al., 1992). | Biological: MOD-5014<br>* MOD-5014, a long-acting modified recombinant Factor VIIa<br>|
| Placebo Comparator: MOD-5014 Placebo<br>Placebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes | Other: MOD-5014 Placebo<br>* Placebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite safety and tolerability parameters as measured by adverse events, electrocardiograms (ECG), Immunogenicity, laboratory results, vital signs and injection site reactions |  | within 30 days of injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of MOD-5014 |  | within 30 days of injection | 
| Tmax of MOD-5014 |  | within 30 days of injection | 
| AUC(0-t) of MOD-5014 |  | within 30 days of injection | 
| AUC(inf) of MOD-5014 |  | within 30 days of injection | 
| T(½) of MOD-5014 |  | within 30 days of injection | 
| Clearance of MOD-5014 |  | within 30 days of injection |