Hemophilia A With InhibitorEarly Phase 1NCT04789954
Study on the Dose-response Relationship of Pharmacodynamic Parameters in Patients With Hemophilia With Inhibitors
A Early Phase 1 study testing Eptacog alfa, activated in people with Hemophilia A With Inhibitor and Hemophilia B With Inhibitor, run by AryoGen Pharmed Co. at 1 site in Iran.
Trial summary
Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors. Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- Hemophilia A With Inhibitor, Hemophilia B With Inhibitor
- What is being tested?
- Eptacog alfa, activated
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteIran
- Study dates
- 29 Dec 2020to 31 Jul 2022
- Phase
- Early 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 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of congenital haemophilia A or B with inhibitors to FVIII or FIX titer >5 Bethesda Units [BU]
- with > 2 episodes of bleeding/year requiring treatment with FVII infusions, not in bleeding episode
- Male adults and adolescents (>12 years)
- Patient informed consent has been obtained [Patients to be enrolled must also provide voluntary written informed consent to the protocol prior to screening to be eligible for the study. For adolescents, parent/legal guardian must provide consent and, wherever possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent].
- Patients willing and able to be hospitalized prior to time of study medication administration for plasma sampling (5 times during the study).
Who cannot join
- Any other type of congenital or acquired coagulopathy, such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
- Antibodies against Factor VII
- Ongoing bleeding prophylaxis regimens with AryoSeven/NovoSeven or planned to occur during the trial
- Platelet count less than 100.000 platelets/mcL (at screening visit)
- Any clinical sign or known history of arterial thrombotic event or deep venous- thrombosis or pulmonary embolism
- HIV positive with current CD4+ count of less than 200/µL
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- Liver cirrhosis
- Factor VIII/IX immune tolerance induction regimen planned to occur during the trial
- Known hypersensitivity to the study medication
- Parallel participation in another experimental drug trial.
- Parallel participation in another marketed drug trial that may affect the primary end-point of the study.
- Concomitant diseases and/or medications, or any other conditions, that render the patient unsuitable for inclusion into the study in the judgement of the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Exploratory Study to Evaluate the Dose Response-Relationship of Pharmacodynamic Parameters of AryoSeven, in Patients With Hemophilia With Inhibitors
Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors.
Read the detailed description
Randomized, double-blind, single dose, 5 ways crossover, clinical trial evaluating four different doses (10 µg/kg, 30 µg/kg, 90 µg/kg, and 270 µg/kg) of AryoSeven (recombinant human FVII activated or eptacog alfa, activated) and one dose of NovoSeven (30 µg/kg) on selected pharmacodynamic parameters (PD) [Primary: Thrombin Generation Assay (TGA)] in male adult and adolescent (>12 years) patients with hemophilia A or B, with an inhibitors titer >5 Bethesda Units [BU] and not in bleeding status. This will be an exploratory study to evaluate dose-response relationship of PD markers as surrogate efficacy endpoints.
- Being tested
- Eptacog alfa, activated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eptacog alfa, activatedBiological
A dose sequence for each injection will be randomly selected from the following doses: 10 μg/kg, 30 μg/kg, 90 μg/kg, or 270 μg/kg, separated by a wash-out period of 3 days.
| Study group | Role | What they receive |
|---|---|---|
| AryoSeven 10 μg/kg | Experimental | Single dose, intravenously Receives: Biological: Eptacog alfa, activated |
| AryoSeven 30 μg/kg | Experimental | Single dose, intravenously Receives: Biological: Eptacog alfa, activated |
| AryoSeven 90 μg/kg | Experimental | Single dose, intravenously Receives: Biological: Eptacog alfa, activated |
| AryoSeven 270 μg/kg | Experimental | Single dose, intravenously Receives: Biological: Eptacog alfa, activated |
| NovoSeven 30 μg/kg | Active comparator | Single dose, intravenously Receives: Biological: Eptacog alfa, activated |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lag time of the thrombin generation curve
Time to 16.7% of peak plasmatic concentration, in minutes.
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
Secondary outcomes (8)
Endogenous Thrombin Potential (PD parameter)
Area under the curve plasma levels of thrombin generation curve (in nmol/per minute)
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
Time to Peak (PD parameter)
Time to Peak of thrombin generation curve (in minutes)
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
Peak height (PD parameter)
Peak height of thrombin generation curve (in nmol/ml)
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
F1.2 prothrombin fragments (PD parameter)
Peak height (micg/L)
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
D-dimer (PD parameter)
Peak height (micg/L)
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
AUCinf (PK parameter)
Area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration;
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
Cmax (PK parameter)
Observed maximum plasma concentration
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
Time of Cmax (PK parameter)
Time of observed maximum plasma concentration
Measured: Up to 30 hours after AryoSeven and NovoSeven injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start29 Dec 2020
- Primary completion13 Aug 2021
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia A With InhibitorStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AryoGen Pharmed Co.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Massimo Iacobelli, MD, Study director, Consultant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04789954
- Sponsor's protocol ID
- UGA 2020-01
- Status last verified
- Sep 2022
- First submitted
- 4 Mar 2021
- Last updated
- 10 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study to Evaluate the Dose Response-Relationship of Pharmacodynamic Parameters of AryoSeven, in Patients With Hemophilia With Inhibitors
- ClinicalTrials.gov ID
- NCT04789954
- Acronym / sponsor ID
- UGA 2020-01
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AryoGen Pharmed Co.Industry (pharma, biotech, devices)
- Study start
- 29 Dec 2020 (actual)
- Primary completion
- 13 Aug 2021 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 10 Mar 2021 (actual)
- 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.
Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors.
Detailed description
Randomized, double-blind, single dose, 5 ways crossover, clinical trial evaluating four different doses (10 µg/kg, 30 µg/kg, 90 µg/kg, and 270 µg/kg) of AryoSeven (recombinant human FVII activated or eptacog alfa, activated) and one dose of NovoSeven (30 µg/kg) on selected pharmacodynamic parameters (PD) [Primary: Thrombin Generation Assay (TGA)] in male adult and adolescent (>12 years) patients with hemophilia A or B, with an inhibitors titer >5 Bethesda Units [BU] and not in bleeding status. This will be an exploratory study to evaluate dose-response relationship of PD markers as surrogate efficacy endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| AryoSeven 10 μg/kg | Experimental | Biological: Eptacog alfa, activatedSingle dose, intravenously |
| AryoSeven 30 μg/kg | Experimental | Biological: Eptacog alfa, activatedSingle dose, intravenously |
| AryoSeven 90 μg/kg | Experimental | Biological: Eptacog alfa, activatedSingle dose, intravenously |
| AryoSeven 270 μg/kg | Experimental | Biological: Eptacog alfa, activatedSingle dose, intravenously |
| NovoSeven 30 μg/kg | Active comparator | Biological: Eptacog alfa, activatedSingle dose, intravenously |
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed diagnosis of congenital haemophilia A or B with inhibitors to FVIII or FIX titer >5 Bethesda Units [BU]
- with > 2 episodes of bleeding/year requiring treatment with FVII infusions, not in bleeding episode
- Male adults and adolescents (>12 years)
- Patient informed consent has been obtained [Patients to be enrolled must also provide voluntary written informed consent to the protocol prior to screening to be eligible for the study. For adolescents, parent/legal guardian must provide consent and, wherever possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent].
- Patients willing and able to be hospitalized prior to time of study medication administration for plasma sampling (5 times during the study).
Key exclusion criteria (12 listed)
- Any other type of congenital or acquired coagulopathy, such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
- Antibodies against Factor VII
- Ongoing bleeding prophylaxis regimens with AryoSeven/NovoSeven or planned to occur during the trial
- Platelet count less than 100.000 platelets/mcL (at screening visit)
- Any clinical sign or known history of arterial thrombotic event or deep venous- thrombosis or pulmonary embolism
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 |
|---|---|---|
| Eptacog alfa, activatedA dose sequence for each injection will be randomly selected from the following doses: 10 μg/kg, 30 μg/kg, 90 μg/kg, or 270 μg/kg, separated by a wash-out period of 3 days. | Biological | AryoSeven 10 μg/kg, AryoSeven 270 μg/kg, AryoSeven 30 μg/kg, AryoSeven 90 μg/kg, NovoSeven 30 μg/kg |
Primary outcome
Lag time of the thrombin generation curve
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Time to 16.7% of peak plasmatic concentration, in minutes.
8 secondary outcomes
Endogenous Thrombin Potential (PD parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Time to Peak (PD parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Peak height (PD parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
F1.2 prothrombin fragments (PD parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
D-dimer (PD parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
AUCinf (PK parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Cmax (PK parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Time of Cmax (PK parameter)
Time frame: Up to 30 hours after AryoSeven and NovoSeven 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 10 Sep 2022.
- Individual participant dataSharing planned: No
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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.
Massimo Iacobelli, MD study director
Consultant
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Eptacog alfa, activated in people with Hemophilia A With Inhibitor and Hemophilia B With Inhibitor, run by AryoGen Pharmed Co. at 1 site in Iran.
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 5 inclusion and 12 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 10 Sep 2022. 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 Iran. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Lag time of the thrombin generation curve (time frame: Up to 30 hours after AryoSeven and NovoSeven injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Sep 2022.