Hemophilia A or B With InhibitorsPhase 1NCT02919800
A Single-dose, Dose-escalation Study of a Long-acting MOD-5014 in Healthy Adult Male
A Phase 1 study testing MOD-5014 in people with Hemophilia A or B With Inhibitors, run by OPKO Health, Inc. at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hemophilia A or B With Inhibitors
- What is being tested?
- MOD-5014
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteIsrael
- Study dates
- 22 Jan 2017to 21 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Hemophilia A or B With Inhibitors
- Being tested
- MOD-5014, MOD-5014 Placebo
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MOD-5014Biological
MOD-5014, a long-acting modified recombinant Factor VIIa
MOD-5014 PlaceboOther
Placebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 Receives: Other: MOD-5014 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite safety and tolerability parameters as measured by adverse events, electrocardiograms (ECG), Immunogenicity, laboratory results, vital signs and injection site reactions
Measured: within 30 days of injection
Secondary outcomes (6)
Cmax of MOD-5014
Measured: within 30 days of injection
Tmax of MOD-5014
Measured: within 30 days of injection
AUC(0-t) of MOD-5014
Measured: within 30 days of injection
AUC(inf) of MOD-5014
Measured: within 30 days of injection
T(½) of MOD-5014
Measured: within 30 days of injection
Clearance of MOD-5014
Measured: within 30 days of injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2016 (estimated)
- Study start22 Jan 2017
- Primary completion21 Feb 2018
- Study completion21 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hemophilia A or B With InhibitorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- OPKO Health, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ramit Arison, Study director, Associate Director Clinical Affairs OPKO Biologics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02919800
- Sponsor's protocol ID
- CP-5-002
- Status last verified
- Sep 2019
- First submitted
- 11 Aug 2016
- Last updated
- 30 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 17880439Fares 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.
PubMed 1374895Fridberg 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.
PubMed 15870545Klitgaard 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.
PubMed 17961193Moss 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.
PubMed 19138379Tanaka KA, Key NS, Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg. 2009 May;108(5):1433-46. doi: 10.1213/ane.0b013e31819bcc9c.
PubMed 19372317
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02919800
- Acronym / sponsor ID
- CP-5-002
- Conditions
- Hemophilia A or B With Inhibitors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- OPKO Health, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Jan 2017 (actual)
- Primary completion
- 21 Feb 2018 (actual)
- Study completion
- 21 Feb 2018 (actual)
- First posted
- 29 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MOD-5014 | Experimental | Biological: MOD-5014MOD-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). |
| MOD-5014 Placebo | Placebo comparator | Other: MOD-5014 PlaceboPlacebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MOD-5014MOD-5014, a long-acting modified recombinant Factor VIIa | Biological | MOD-5014 |
| MOD-5014 PlaceboPlacebo solution for SC injection containing the same inactive ingredients used in the active drug product at matching volumes | Other | MOD-5014 Placebo |
Primary outcome
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
6 secondary outcomes
Cmax of MOD-5014
Time frame: within 30 days of injection
Tmax of MOD-5014
Time frame: within 30 days of injection
AUC(0-t) of MOD-5014
Time frame: within 30 days of injection
AUC(inf) of MOD-5014
Time frame: within 30 days of injection
T(½) of MOD-5014
Time frame: within 30 days of injection
Clearance of MOD-5014
Time frame: within 30 days of injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2019.
- Results publication: PubMed 17880439Bysted 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 publication: PubMed 1374895Fares 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 publication: PubMed 15870545Fridberg 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 publication: PubMed 17961193Klitgaard 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 publication: PubMed 19138379Moss 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 publication: PubMed 19372317Tanaka KA, Key NS, Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg. 2009 May;108(5):1433-46. doi: 10.1213/ane.0b013e31819bcc9c.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramit Arison study director
Associate Director Clinical Affairs OPKO Biologics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MOD-5014 in people with Hemophilia A or B With Inhibitors, run by OPKO Health, Inc. at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02919800, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2019.