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

Primary Purpose

Hemophilia A or B With Inhibitors

Status

Completed

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

MOD-5014

MOD-5014 Placebo

About this trial

This is an interventional other trial for Hemophilia A or B With Inhibitors

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

TASMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MOD-5014

MOD-5014 Placebo

Arm Description

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).

Placebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes

Outcomes

Primary Outcome Measures

Composite safety and tolerability parameters as measured by adverse events, electrocardiograms (ECG), Immunogenicity, laboratory results, vital signs and injection site reactions

Secondary Outcome Measures

Cmax of MOD-5014

Tmax of MOD-5014

AUC(0-t) of MOD-5014

AUC(inf) of MOD-5014

T(½) of MOD-5014

Clearance of MOD-5014

Full Information

NCT ID

NCT02919800

First Posted

August 11, 2016

Last Updated

September 27, 2019

Sponsor

OPKO Health, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02919800

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

January 22, 2017 (Actual)

Primary Completion Date

February 21, 2018 (Actual)

Study Completion Date

February 21, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

OPKO Health, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia A or B With Inhibitors

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MOD-5014

Arm Type

Experimental

Arm Description

Arm Title

MOD-5014 Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes

Intervention Type

Biological

Intervention Name(s)

MOD-5014

Intervention Description

MOD-5014, a long-acting modified recombinant Factor VIIa

Intervention Type

Other

Intervention Name(s)

MOD-5014 Placebo

Intervention Description

Placebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes

Primary Outcome Measure Information:

Title

Composite safety and tolerability parameters as measured by adverse events, electrocardiograms (ECG), Immunogenicity, laboratory results, vital signs and injection site reactions

Time Frame

within 30 days of injection

Secondary Outcome Measure Information:

Title

Cmax of MOD-5014

Time Frame

within 30 days of injection

Title

Tmax of MOD-5014

Time Frame

within 30 days of injection

Title

AUC(0-t) of MOD-5014

Time Frame

within 30 days of injection

Title

AUC(inf) of MOD-5014

Time Frame

within 30 days of injection

Title

T(½) of MOD-5014

Time Frame

within 30 days of injection

Title

Clearance of MOD-5014

Time Frame

within 30 days of injection

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ramit Arison

Organizational Affiliation

Associate Director Clinical Affairs OPKO Biologics

Official's Role

Study Director

Facility Information:

Facility Name

TASMC

City

Tel-Aviv

Country

Israel

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

17880439

Citation

Bysted BV, Scharling B, Moller T, Hansen BL. A randomized, double-blind trial demonstrating bioequivalence of the current recombinant activated factor VII formulation and a new robust 25 degrees C stable formulation. Haemophilia. 2007 Sep;13(5):527-32. doi: 10.1111/j.1365-2516.2007.01516.x.

Results Reference

result

PubMed Identifier

1374895

Citation

Fares FA, Suganuma N, Nishimori K, LaPolt PS, Hsueh AJ, Boime I. Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4304-8. doi: 10.1073/pnas.89.10.4304.

Results Reference

result

PubMed Identifier

15870545

Citation

Fridberg MJ, Hedner U, Roberts HR, Erhardtsen E. A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects. Blood Coagul Fibrinolysis. 2005 Jun;16(4):259-66. doi: 10.1097/01.mbc.0000169218.15926.34.

Results Reference

result

PubMed Identifier

17961193

Citation

Klitgaard T, Nielsen TG. Overview of the human pharmacokinetics of recombinant activated factor VII. Br J Clin Pharmacol. 2008 Jan;65(1):3-11. doi: 10.1111/j.1365-2125.2007.03030.x. Epub 2007 Oct 24.

Results Reference

result

PubMed Identifier

19138379

Citation

Moss J, Scharling B, Ezban M, Moller Sorensen T. Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects. J Thromb Haemost. 2009 Feb;7(2):299-305. doi: 10.1111/j.1538-7836.2008.03253.x. Epub 2008 Dec 3.

Results Reference

result

PubMed Identifier

19372317

Citation

Tanaka KA, Key NS, Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg. 2009 May;108(5):1433-46. doi: 10.1213/ane.0b013e31819bcc9c.

Results Reference

result

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

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