Severe Hemophilia APhase 1/2NCT04046848
Safety and Pharmacokinetics of Subcutaneous Injection of OCTA101 in Adult Patients With Severe Hemophilia A
A Phase 1/2 study testing OCTA101 in people with Severe Hemophilia A, run by Octapharma at 1 site in Bulgaria.
Trial summary
This Phase 1/2 study will be a dose escalation study in adults in 5 cohorts (named cohorts 1, 2, 3, 5 and 6), with the main purpose to assess the safety of subcutaneous injection of OCTA101 (a human-cl rhFVIII and recombinant human von Willebrand Factor fragment dimer) in previously treated adult patients with severe… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Severe Hemophilia A
- What is being tested?
- OCTA101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteBulgaria
- Study dates
- 3 Jul 2019to 18 Feb 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe hemophilia A (<1% FVIII:C) as documented in medical records
- Males ≥18 years of age
- Subjects who have had ≥150 exposure days (EDs) with a FVIII product
- Written informed consent for study participation obtained before undergoing any study specific procedures
Who cannot join
- Previous participation in this trial
- Use of an Investigational Medicinal Product within 30 days prior to the first OCTA101 injection
- History of FVIII inhibitors titre ≥0.6 BU/mL defined by medical records
- Inhibitors to FVIII (≥0.6 BU/mL) at screening measured by Nijmegen modified Bethesda method at central laboratory
- Human immunodeficiency virus (HIV) positive subjects with a CD4+ count <200/mL
- Clinically significant anemia at screening (hemoglobin <8 g/dL)
Show all 13Show fewer
- Presence of any significant comorbidity (at the discretion of the investigator) that might confound the interpretation of the study data and/or that might put the patient at undue risk by participating in the trial
- Any coagulation disorder other than hemophilia A
- AST or ALT levels >3 times the upper limit of normal
- Creatinine >120 μmol/L
- Platelet count <100,000 μL
- BMI ≥30 kg/m²
- For Cohort 6, patients with a positive LumiTope test at screening will be excluded
Trial locations and contacts
1 site in 1 country.
Bulgaria1 site
Specialized Hospital for Active Treatment of Hematological Diseases EAD Clinic of Clinical Hematology
Sofia
About this study
Official title: Phase 1/2 Study to Assess the Safety and Pharmacokinetics of Subcutaneous Injection of OCTA101 in Previously Treated Adult Patients With Severe Hemophilia A
This Phase 1/2 study will be a dose escalation study in adults in 5 cohorts (named cohorts 1, 2, 3, 5 and 6), with the main purpose to assess the safety of subcutaneous injection of OCTA101 (a human-cl rhFVIII and recombinant human von Willebrand Factor fragment dimer) in previously treated adult patients with severe hemophilia A. The study also aims to assess the pharmacokinetics (PK) characteristics, dose proportionality, and subcutaneous bioavailability of OCTA101 compared with intravenous administration of Nuwiq (Human-cl rh FVIII), in order to define the prophylactic treatment (dose and injection interval) that would result in protective trough levels of FVIII:C for future Phase 3 studies. Cohorts 1, 2, 3 and 5 will undergo a single injection of OCTA101, with cohorts 1, 2 and 3 proceeding to 3-month daily dosing prophylactic treatment for 3 months by Data Monitoring Committee recommendation. Cohorts 1 and 2 will undergo a further PK at the end of the daily injection period. A further cohort, cohort 6, will have an initial 4 to 6-week run-in treatment period with Nuwiq intravenous prophylaxis followed by 12.5 IU/kg OCTA101 subcutaneous daily prophylaxis for >3 up to 6-7 months.
- Conditions
- Severe Hemophilia A
- Being tested
- OCTA101
- Keywords
- Hemophilia A, Blood Coagulation Disorders, Inherited, Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn, Factor VIII
- Medical subject headings
- Hemophilia A, Blood Coagulation Disorders, Inherited, Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OCTA101Drug
OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. Receives: Drug: OCTA101 |
| Cohort 2 | Experimental | 100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. Receives: Drug: OCTA101 |
| Cohort 3 | Experimental | 50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. Receives: Drug: OCTA101 |
| Cohort 5 | Experimental | (n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence. Receives: Drug: OCTA101 |
| Cohort 6 | Experimental | (n=16): Following an initial 4 to 6-week run-in period with Nuwiq iv prophylaxis, >3-6 months daily prophylactic treatment with 12.5 IU/kg OCTA101 sc, then 25 IU/kg OCTA101 sc for a further 6-7 months (exact dosing depends on available vial sizes). In case of two spontaneous bleeding episodes, after having completed at least 3 months with 12.5 IU/kg OCTA101 daily treatment the individual treatment dose will be increased from 12.5 to 25 IU/kg. Site of administration (abdomen or thigh) to be chosen by the patient. A further treatment phase with 40 IU/kg OCTA101 will be discussed with the DMC, once results of earlier dosing phases are available. Receives: Drug: OCTA101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients Experiencing Adverse Events
Measured: Approximately 4 months; up to 11 months for cohort 6
Participants Experiencing Dose-limiting Toxicities (DLTs)
Pre-defined DLTs for this study are: 1. Severe allergic reactions at least possibly related to study drug. 2. Severe vital organ toxicity at least possibly related to study drug that does not resolve to at least mild severity within 48 to 72 hours. 3. Any treatment-emergent severe toxicity at least possibly related to study drug other than the toxicities referenced in 2) that does not decrease to mild or resolve within 7 days
Measured: Approximately 4 months; up to 11 months for cohort 6
Patients Experiencing Thromboembolic Events
The definition of the cluster thromboembolic events was based on the standardised MedDRA query (SMQ) "Embolic and thrombotic events":
Definition: Thrombotic disorders are diseases characterized by formation of a thrombus that obstructs vascular blood flow locally or detaches and embolizes to occlude blood flow downstream. Embolism is the sudden blocking of a vessel by a clot or foreign material which has been brought to its site of lodgment by the blood current. (Thrombo-)phlebitis is an inflammation of a vein (phlebitis) associated with thrombus formation (thrombosis).
This SMQ includes 3 sub-SMQ:
- Embolic and thrombotic events, venous (SMQ)
- Embolic and thrombotic events, arterial (SMQ)
- Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous (SMQ)
Measured: Approximately 4 months; up to 11 months for cohort 6
Patients Experiencing Local Injection Site Reactions of Any Grade
Investigator (and patient in case of home treatment) assessed local injection reactivity directly after injection and at 15 ± 5 min post-injection as per the ISO10999-10 standard:
0=no skin reactivity;
- mild (subject is aware of the signs/symptoms, but finds it easily tolerated)
- moderate (discomfort enough to cause interference with usual activities)
- severe (subject is incapacitated and unable to work or participate in many or all usual activities).
Measured: Approximately 4 months; up to 11 months for cohort 6. Local injection site reactions were captured throughout the period where OCTA-101 was injected subcutaneously (sc).
Inhibitor Formation to FVIII
Development of an inhibitor was defined as a neutralizing antibody value of greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL) identified and confirmed by a second test on an independent sample. In case of positive inhibitor results, inhibitor retesting using a second, separately drawn sample was to be performed, preferably within 15 days of becoming aware of the positive result. Both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
Measured: From first injection to 4 months after start of of daily injection (cohorts 1, 2 and 3), 4 weeks after last PK injection (cohort 5), monthly during the daily sc treatment period (cohort 6)
Secondary outcomes (27)
Efficacy: Area Under the Concentration-time Curve (AUC) of FVIII:C
Mean AUC of FVIII after PK injection of OCTA101 as measured by chromogenic assay.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Maximum Plasma Concentration (Cmax) of FVIII:C
Maximum observed concentration of FVIII:C after PK injection of OCTA101 as measured by chromogenic assay.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of FVIII:C
Time of occurrence of Cmax after PK injection of OCTA101 as measured by chromogenic assay.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
In Vivo Recovery (IVR) of FVIII:C
In vivo recovery (IVR) = dose-normalised and body weight-normalised maximum gain in FVIII:C (IU/dL per IU/kg)
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Half-life (t1/2) of FVIII:C
Apparent terminal log-linear half-life of FVIII:C after PK injection of OCTA101 as measured by chromogenic assay.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Mean Residence Time (MRT) of FVIII:C
The average time at which the number of absorbed FVIII molecules reside in the body, after PK injection of OCTA101 as measured by chromogenic assay.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Area Under the Concentration-time Curve (AUC(0-tz)) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Maximum Plasma Concentration (Cmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: In Vivo Recovery (IVR) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
In vivo recovery (IVR) = dose-normalised and body weight-normalised maximum gain in OCTA-12 (ug/dL per ug/kg).
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Half Life (t1/2) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: t(1/2) could not be determined for OTCA12 as the OCTA12 concentrations had not yet declined during the observation time prior to prior to end of sampling period.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Mean Residence Time (MRT) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Note: MRT could not be determined for OCTA12 as the OCTA12 concentrations had not yet declined during the observation time prior to end of sampling period.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Total Annualized Bleeding Rate
Total annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3 An estimated total annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate for cohort 6.
Measured: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93).
Efficacy: Spontaneous Annualized Bleeding Rate
Spontaneous annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total spontaneous annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate
Measured: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Total Annualized Treated Bleeding Rate
Total annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total annualized treated bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
Measured: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Spontaneous Annualized Treated Bleeding Rate
Spontaneous annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3.
An estimated total spontaneous annualized treated bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
Measured: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Traumatic Annualized Bleeding Rate
Traumatic annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total traumatic annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
Measured: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Joint Annualized Bleeding Rate
Joint annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3.
An estimated total joint annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
Measured: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: FVIII:C Trough and Peak Plasma Levels
FVIII:C trough and peak plasma levels during daily dosing for cohorts 1, 2, 3 and 6
Measured: 3 months; maximally 6 months for cohort 6
Efficacy: Efficacy of Treatment of Bleeding Episodes Using Score (4-point).
Score (4-point) to assess the efficacy of treatment of bleeding episodes with Human-cl rhFVIII. Treatment efficacy will be assessed using predefined criteria to score either 'Excellent', 'Good', 'Moderate' or 'None'. All efficacy ratings assessed as either 'excellent' or 'good' will be considered 'successfully treated'.
Measured: 5 days to approximately 11 months
Safety: Antibody Formation to OCTA12
Samples were checked for the presence of antibodies to OCTA12 by using a validated ELISA in a central lab.
Measured: From 0 hours (pre-dose) to 72 hours (cohorts 1,2,3,5) or 96 hours (cohort 2).
Safety: OCTA12 Plasma Levels
OCTA12 plasma levels during daily dosing (cohorts 1, 2, 3 and 6).
Measured: 3 months; maximally 6 months for cohort 6
Safety: Change in Hemoglobin
Number of Participants with changes in hemoglobin levels that were considered as Adverse Events.
Measured: 5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Safety: Change in Alanine Aminotransferase (ALT)
Alanine aminotransferase (ALT) compared to baseline, measured in U/L. Number of Participants with changes in ALT that were considered as Adverse Events.
Measured: 5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Safety: Change in Aspartate Transaminase (AST)
Aspartate transaminase (AST) compared to baseline, measured in U/l. Number of Participants with changes in AST that were considered as Adverse Events.
Measured: 5 days to approximately 11 months
Patients With Changes to Vital Signs
Vitals signs changes from baseline, reported as AEs. Number of Participants with changes to vital signs that were considered as Adverse Events.
Measured: 5 days to approximately 11 months
Patients With Changes in Physical Examination Results
Number of Participants with changes to their physical examination results from baseline that were considered as Adverse Events
Measured: 5 days to approximately 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2019
- Study start3 Jul 2019
- Primary completion18 Feb 2022
- Study completion18 Feb 2022
Why it stopped: Study was terminated due to SADRs
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Severe Hemophilia AStudies of the same condition, open and under way.
- More trials run by OctapharmaThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Octapharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04046848
- Sponsor's protocol ID
- SubQ8-01
- Status last verified
- Jan 2025
- First submitted
- 18 Jul 2019
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cannavo A, Valsecchi C, Garagiola I, Palla R, Mannucci PM, Rosendaal FR, Peyvandi F; SIPPET study group. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A. Blood. 2017 Mar 9;129(10):1245-1250. doi: 10.1182/blood-2016-06-720086. Epub 2016 Dec 29.
PubMed 28034891Gibaldi M. (1991) Biopharmaceutics and Clinical Pharmacokinetics. 4th Edition, Lea and Febiger, Philadelphia, Appendix II.
Liesner RJ, Abashidze M, Aleinikova O, Altisent C, Belletrutti MJ, Borel-Derlon A, Carcao M, Chambost H, Chan AKC, Dubey L, Ducore J, Fouzia NA, Gattens M, Gruel Y, Guillet B, Kavardakova N, El Khorassani M, Klukowska A, Lambert T, Lohade S, Sigaud M, Turea V, Wu JKM, Vdovin V, Pavlova A, Jansen M, Belyanskaya L, Walter O, Knaub S, Neufeld EJ. Immunogenicity, efficacy and safety of Nuwiq(R) (human-cl rhFVIII) in previously untreated patients with severe haemophilia A-Interim results from the NuProtect Study. Haemophilia. 2018 Mar;24(2):211-220. doi: 10.1111/hae.13320. Epub 2017 Aug 16.
PubMed 28815880Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, Forgue ST. Confidence interval criteria for assessment of dose proportionality. Pharm Res. 2000 Oct;17(10):1278-83. doi: 10.1023/a:1026451721686.
PubMed 11145235Wagner JG (1975) Fundamentals of clinical pharmacokinetics. Drug Intelligence Publications, Inc. Hamilton, IL, USA
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study to Assess the Safety and Pharmacokinetics of Subcutaneous Injection of OCTA101 in Previously Treated Adult Patients With Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT04046848
- Acronym / sponsor ID
- SubQ8-01
- Conditions
- Severe Hemophilia A
- Keywords
- Hemophilia A, Blood Coagulation Disorders, Inherited, Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn, Factor VIII
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to SADRs
- Enrolment
- 36 participants (actual)
- Lead sponsor
- OctapharmaIndustry (pharma, biotech, devices)
- Study start
- 3 Jul 2019 (actual)
- Primary completion
- 18 Feb 2022 (actual)
- Study completion
- 18 Feb 2022 (actual)
- First posted
- 6 Aug 2019 (actual)
- Results
- Posted 13 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 1/2 study will be a dose escalation study in adults in 5 cohorts (named cohorts 1, 2, 3, 5 and 6), with the main purpose to assess the safety of subcutaneous injection of OCTA101 (a human-cl rhFVIII and recombinant human von Willebrand Factor fragment dimer) in previously treated adult patients with severe hemophilia A. The study also aims to assess the pharmacokinetics (PK) characteristics, dose proportionality, and subcutaneous bioavailability of OCTA101 compared with intravenous administration of Nuwiq (Human-cl rh FVIII), in order to define the prophylactic treatment (dose and injection interval) that would result in protective trough levels of FVIII:C for future Phase 3 studies. Cohorts 1, 2, 3 and 5 will undergo a single injection of OCTA101, with cohorts 1, 2 and 3 proceeding to 3-month daily dosing prophylactic treatment for 3 months by Data Monitoring Committee recommendation. Cohorts 1 and 2 will undergo a further PK at the end of the daily injection period. A further cohort, cohort 6, will have an initial 4 to 6-week run-in treatment period with Nuwiq intravenous prophylaxis followed by 12.5 IU/kg OCTA101 subcutaneous daily prophylaxis for >3 up to 6-7 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: OCTA10150 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A. Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. |
| Cohort 2 | Experimental | Drug: OCTA101100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A. Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. |
| Cohort 3 | Experimental | Drug: OCTA10150 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A. Treatments will be administered in fixed sequence, with Human-cl rhFVIII first. Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. |
| Cohort 5 | Experimental | Drug: OCTA101(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence. |
| Cohort 6 | Experimental | Drug: OCTA101(n=16): Following an initial 4 to 6-week run-in period with Nuwiq iv prophylaxis, >3-6 months daily prophylactic treatment with 12.5 IU/kg OCTA101 sc, then 25 IU/kg OCTA101 sc for a further 6-7 months (exact dosing depends on available vial sizes). In case of two spontaneous bleeding episodes, after having completed at least 3 months with 12.5 IU/kg OCTA101 daily treatment the individual treatment dose will be increased from 12.5 to 25 IU/kg. Site of administration (abdomen or thigh) to be chosen by the patient. A further treatment phase with 40 IU/kg OCTA101 will be discussed with the DMC, once results of earlier dosing phases are available. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Severe hemophilia A (<1% FVIII:C) as documented in medical records
- Males ≥18 years of age
- Subjects who have had ≥150 exposure days (EDs) with a FVIII product
- Written informed consent for study participation obtained before undergoing any study specific procedures
Key exclusion criteria (13 listed)
- Previous participation in this trial
- Use of an Investigational Medicinal Product within 30 days prior to the first OCTA101 injection
- History of FVIII inhibitors titre ≥0.6 BU/mL defined by medical records
- Inhibitors to FVIII (≥0.6 BU/mL) at screening measured by Nijmegen modified Bethesda method at central laboratory
- Human immunodeficiency virus (HIV) positive subjects with a CD4+ count <200/mL
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 |
|---|---|---|
| OCTA101OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer). | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 5, Cohort 6 |
Primary outcome
Patients Experiencing Adverse Events
Time frame: Approximately 4 months; up to 11 months for cohort 6
Participants Experiencing Dose-limiting Toxicities (DLTs)
Time frame: Approximately 4 months; up to 11 months for cohort 6
Pre-defined DLTs for this study are: 1. Severe allergic reactions at least possibly related to study drug. 2. Severe vital organ toxicity at least possibly related to study drug that does not resolve to at least mild severity within 48 to 72 hours. 3. Any treatment-emergent severe toxicity at least possibly related to study drug other than the toxicities referenced in 2) that does not decrease to mild or resolve within 7 days
Patients Experiencing Thromboembolic Events
Time frame: Approximately 4 months; up to 11 months for cohort 6
The definition of the cluster thromboembolic events was based on the standardised MedDRA query (SMQ) "Embolic and thrombotic events": Definition: Thrombotic disorders are diseases characterized by formation of a thrombus that obstructs vascular blood flow locally or detaches and embolizes to occlude blood flow downstream. Embolism is the sudden blocking of a vessel by a clot or foreign material which has been brought to its site of lodgment by the blood current. (Thrombo-)phlebitis is an inflammation of a vein (phlebitis) associated with thrombus formation (thrombosis). This SMQ includes 3 sub-SMQ: * Embolic and thrombotic events, venous (SMQ) * Embolic and thrombotic events, arterial (SMQ) * Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous (SMQ)
Patients Experiencing Local Injection Site Reactions of Any Grade
Time frame: Approximately 4 months; up to 11 months for cohort 6. Local injection site reactions were captured throughout the period where OCTA-101 was injected subcutaneously (sc).
Investigator (and patient in case of home treatment) assessed local injection reactivity directly after injection and at 15 ± 5 min post-injection as per the ISO10999-10 standard: 0=no skin reactivity; 1. mild (subject is aware of the signs/symptoms, but finds it easily tolerated) 2. moderate (discomfort enough to cause interference with usual activities) 3. severe (subject is incapacitated and unable to work or participate in many or all usual activities).
Inhibitor Formation to FVIII
Time frame: From first injection to 4 months after start of of daily injection (cohorts 1, 2 and 3), 4 weeks after last PK injection (cohort 5), monthly during the daily sc treatment period (cohort 6)
Development of an inhibitor was defined as a neutralizing antibody value of greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL) identified and confirmed by a second test on an independent sample. In case of positive inhibitor results, inhibitor retesting using a second, separately drawn sample was to be performed, preferably within 15 days of becoming aware of the positive result. Both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
27 secondary outcomes
Efficacy: Area Under the Concentration-time Curve (AUC) of FVIII:C
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Maximum Plasma Concentration (Cmax) of FVIII:C
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of FVIII:C
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
In Vivo Recovery (IVR) of FVIII:C
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Half-life (t1/2) of FVIII:C
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Mean Residence Time (MRT) of FVIII:C
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Area Under the Concentration-time Curve (AUC(0-tz)) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Maximum Plasma Concentration (Cmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: In Vivo Recovery (IVR) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Half Life (t1/2) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Mean Residence Time (MRT) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Total Annualized Bleeding Rate
Time frame: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93).
Efficacy: Spontaneous Annualized Bleeding Rate
Time frame: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Total Annualized Treated Bleeding Rate
Time frame: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Spontaneous Annualized Treated Bleeding Rate
Time frame: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Traumatic Annualized Bleeding Rate
Time frame: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Joint Annualized Bleeding Rate
Time frame: The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: FVIII:C Trough and Peak Plasma Levels
Time frame: 3 months; maximally 6 months for cohort 6
Efficacy: Efficacy of Treatment of Bleeding Episodes Using Score (4-point).
Time frame: 5 days to approximately 11 months
Safety: Antibody Formation to OCTA12
Time frame: From 0 hours (pre-dose) to 72 hours (cohorts 1,2,3,5) or 96 hours (cohort 2).
Safety: OCTA12 Plasma Levels
Time frame: 3 months; maximally 6 months for cohort 6
Safety: Change in Hemoglobin
Time frame: 5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Safety: Change in Alanine Aminotransferase (ALT)
Time frame: 5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Safety: Change in Aspartate Transaminase (AST)
Time frame: 5 days to approximately 11 months
Patients With Changes to Vital Signs
Time frame: 5 days to approximately 11 months
Patients With Changes in Physical Examination Results
Time frame: 5 days to approximately 11 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28034891Cannavo A, Valsecchi C, Garagiola I, Palla R, Mannucci PM, Rosendaal FR, Peyvandi F; SIPPET study group. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A. Blood. 2017 Mar 9;129(10):1245-1250. doi: 10.1182/blood-2016-06-720086. Epub 2016 Dec 29.
- BackgroundGibaldi M. (1991) Biopharmaceutics and Clinical Pharmacokinetics. 4th Edition, Lea and Febiger, Philadelphia, Appendix II.
- Background: PubMed 28815880Liesner RJ, Abashidze M, Aleinikova O, Altisent C, Belletrutti MJ, Borel-Derlon A, Carcao M, Chambost H, Chan AKC, Dubey L, Ducore J, Fouzia NA, Gattens M, Gruel Y, Guillet B, Kavardakova N, El Khorassani M, Klukowska A, Lambert T, Lohade S, Sigaud M, Turea V, Wu JKM, Vdovin V, Pavlova A, Jansen M, Belyanskaya L, Walter O, Knaub S, Neufeld EJ. Immunogenicity, efficacy and safety of Nuwiq(R) (human-cl rhFVIII) in previously untreated patients with severe haemophilia A-Interim results from the NuProtect Study. Haemophilia. 2018 Mar;24(2):211-220. doi: 10.1111/hae.13320. Epub 2017 Aug 16.
- Background: PubMed 11145235Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, Forgue ST. Confidence interval criteria for assessment of dose proportionality. Pharm Res. 2000 Oct;17(10):1278-83. doi: 10.1023/a:1026451721686.
- BackgroundWagner JG (1975) Fundamentals of clinical pharmacokinetics. Drug Intelligence Publications, Inc. Hamilton, IL, USA
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OCTA101 in people with Severe Hemophilia A, run by Octapharma at 1 site in Bulgaria.
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 4 inclusion and 13 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: stopped early, as of the sponsor's last update on 15 Oct 2026. 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 Bulgaria. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Patients Experiencing Adverse Events (time frame: Approximately 4 months; up to 11 months for cohort 6). The study lists 5 primary outcomes in all. 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 NCT04046848, which also lists 5 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 15 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.