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

NCT02919800 | Completed Phase 1 DMC

• 1 other identifier: CP-5-002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophilia A or B With Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (2)

MOD-5014

EXPERIMENTAL

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

MOD-5014 Placebo

PLACEBO COMPARATOR

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

Other: MOD-5014 Placebo

Interventions

MOD-5014 BIOLOGICAL

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

MOD-5014

MOD-5014 Placebo OTHER

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

MOD-5014 Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• OPKO Health, Inc.: lead

Study Sites (1)

TASMC

Tel Aviv, Israel

Location

Related Publications (6)

• 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.

  PMID: 17880439 RESULT

• 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.

  PMID: 1374895 RESULT

• 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.

  PMID: 15870545 RESULT

• 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.

  PMID: 17961193 RESULT

• 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.

  PMID: 19138379 RESULT

• 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.

  PMID: 19372317 RESULT

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ramit Arison

  Associate Director Clinical Affairs OPKO Biologics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2016
• First Posted: September 29, 2016
• Study Start: January 22, 2017
• Primary Completion: February 21, 2018
• Study Completion: February 21, 2018
• Last Updated: September 30, 2019

Record last verified: 2019-09

Locations

IL (1)