Hemophilia APhase 1NCT02035605
A Phase 1 Study of an Investigational Drug, ALN-AT3SC, in Healthy Volunteers and Hemophilia A or B Patients
A Phase 1 study testing ALN-AT3SC and Sterile Normal Saline (0.9% NaCl) in people with Hemophilia A and Hemophilia B, run by Sanofi at 14 sites in 5 countries.
Trial summary
The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of ALN-AT3SC in healthy volunteers and Hemophilia A or B patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hemophilia A, Hemophilia B
- What is being tested?
- ALN-AT3SC and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 14 sitesin 5 countries
- Study dates
- 20 Jan 2014to 20 Jul 2017
- 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 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Part A (SAD phase) inclusion:
- Healthy adult males aged 18 to 40 years inclusive at Screening.
- Subjects with adequate complete blood counts and liver function tests.
- Willing to provide written informed consent and willing to comply with study requirements.
- Part B \& C (MAD \& MD phase) inclusion:
- Adult male hemophilia patients aged 18 to 65 years inclusive at Screening.
Show all 12Show fewer
- Patients with adequate complete blood counts and liver function tests.
- Patients with moderate or severe, clinically stable hemophilia A or B (Factor VIII or Factor IX ≤5%).
- Willing to provide written informed consent and willing to comply with study requirements
- Part D (MD Phase in patients with inhibitors) Inclusion:
- Same as Parts B/C
- A Bethesda inhibitor assay > 0.6 BU/mL
Who cannot join
- Part A (SAD phase) exclusion:
- Subjects with a personal history and/or family history of venous thromboembolism (VTE)
- Subjects with a known co-existing thrombophilic disorder
- Subjects with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- Subjects with a history of serious mental illness that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
- Subjects who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological including osteoarthritis and other inflammatory diseases, dermatological including rash, eczema, dermatitis, or connective tissue diseases or disorders.
Show all 15Show fewer
- Part B \& C (MAD \& MD phase) exclusion:
- Patients with a current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity.
- Patients who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory or other diseases that in the judgment of the investigator precludes their participation in the study.
- Patients with a known co-existing thrombophilic disorder
- Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- Patients who are known to be HIV positive and have a CD4 count <400 cells/μL
- Part D (MD Phase in patients with inhibitors) exclusion:
- Same as Parts B/C
- Patients who are known to be HIV positive and have a CD4 count <200 cells/μL
Trial locations and contacts
14 sites in 5 countries.
14 sites in 5 countries
United Kingdom5 sites
Clinical Trial Site
Glasgow
Clinical Trial Site
London, NW3 2QG
Clinical Trial Site
London, SE1 1YR
Clinical Trial Site
Manchester
Clinical Trial Site
Truro
Bulgaria3 sites
Clinical Trial Site
Plovdiv
Clinical Trial Site
Sofia
Clinical Trial Site
Varna
Russia3 sites
Clinical Trial Site
Kirov
Clinical Trial Site
Moscow
Clinical Trial Site
Saint Petersburg
Switzerland2 sites
Clinical Trial Site
Sankt Gallen
Clinical Trial Site
Zurich
About this study
Official title: A Phase 1 Single-ascending and Multiple-ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Subcutaneously Administered ALN-AT3SC in Healthy Adult Volunteers and Hemophilia A or B Patients (Moderate or Severe Hemophilia)
The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of ALN-AT3SC in healthy volunteers and Hemophilia A or B patients.
- Conditions
- Hemophilia A, Hemophilia B
- Being tested
- ALN-AT3SC, Sterile Normal Saline (0.9% NaCl)
- Medical subject headings
- Hemophilia A, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-AT3SCDrug
Ascending doses of ALN-AT3SC by subcutaneous (sc) injection
Sterile Normal Saline (0.9% NaCl)Drug
Calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| ALN-AT3SC | Active comparator | Not described Receives: Drug: ALN-AT3SC |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Not described Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of ALN-AT3SC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and AEs leading to study drug discontinuation.
Measured: Part A (SAD phase): through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
Secondary outcomes (3)
The pharmacokinetics (PK) of ALN-AT3SC as characterized by plasma PK profiles and urine samples.
Measured: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma AT levels.
Measured: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma TG.
Measured: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2014 (estimated)
- Study start20 Jan 2014
- Primary completion20 Jul 2017
- Study completion20 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by SanofiThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kate Madigan, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02035605
- Sponsor's protocol ID
- ALN-AT3SC-001
- Status last verified
- Jun 2018
- First submitted
- 13 Jan 2014
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900.
PubMed 39642315Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I, Kazmi R, Chowdary P, Gercheva-Kyuchukova L, Mamonov V, Timofeeva M, Soh CH, Garg P, Vaishnaw A, Akinc A, Sorensen B, Ragni MV. Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med. 2017 Aug 31;377(9):819-828. doi: 10.1056/NEJMoa1616569. Epub 2017 Jul 10.
PubMed 28691885
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Single-ascending and Multiple-ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Subcutaneously Administered ALN-AT3SC in Healthy Adult Volunteers and Hemophilia A or B Patients (Moderate or Severe Hemophilia)
- ClinicalTrials.gov ID
- NCT02035605
- Acronym / sponsor ID
- ALN-AT3SC-001
- Conditions
- Hemophilia A, Hemophilia B
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 20 Jan 2014 (actual)
- Primary completion
- 20 Jul 2017 (actual)
- Study completion
- 20 Jul 2017 (actual)
- First posted
- 14 Jan 2014 (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.
The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of ALN-AT3SC in healthy volunteers and Hemophilia A or B patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALN-AT3SC | Active comparator | Drug: ALN-AT3SC |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Healthy adult males aged 18 to 40 years inclusive at Screening.
- Subjects with adequate complete blood counts and liver function tests.
- Willing to provide written informed consent and willing to comply with study requirements.
- Adult male hemophilia patients aged 18 to 65 years inclusive at Screening.
- Patients with adequate complete blood counts and liver function tests.
Key exclusion criteria (15 listed)
- Subjects with a personal history and/or family history of venous thromboembolism (VTE)
- Subjects with a known co-existing thrombophilic disorder
- Subjects with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- Subjects with a history of serious mental illness that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
- Subjects who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological including osteoarthritis and other inflammatory diseases, dermatological including rash, eczema, dermatitis, or connective tissue diseases or disorders.
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 |
|---|---|---|
| ALN-AT3SCAscending doses of ALN-AT3SC by subcutaneous (sc) injection | Drug | ALN-AT3SC |
| Sterile Normal Saline (0.9% NaCl)Calculated volume to match active comparator | Drug | Sterile Normal Saline (0.9% NaCl) |
Primary outcome
The safety of ALN-AT3SC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and AEs leading to study drug discontinuation.
Time frame: Part A (SAD phase): through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
3 secondary outcomes
The pharmacokinetics (PK) of ALN-AT3SC as characterized by plasma PK profiles and urine samples.
Time frame: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma AT levels.
Time frame: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma TG.
Time frame: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
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 19 Dec 2020.
- Derived from this study: PubMed 39642315Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900.
- Derived from this study: PubMed 28691885Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I, Kazmi R, Chowdary P, Gercheva-Kyuchukova L, Mamonov V, Timofeeva M, Soh CH, Garg P, Vaishnaw A, Akinc A, Sorensen B, Ragni MV. Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med. 2017 Aug 31;377(9):819-828. doi: 10.1056/NEJMoa1616569. Epub 2017 Jul 10.
- Individual participant dataSharing planned: Undecided
Related trials for Hemophilia A
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
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.
Kate Madigan, MD study director
Alnylam Pharmaceuticals
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALN-AT3SC and Sterile Normal Saline (0.9% NaCl) in people with Hemophilia A and Hemophilia B, run by Sanofi at 14 sites in 5 countries.
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 12 inclusion and 15 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United Kingdom, Bulgaria, Russia, Switzerland, United States. 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?
The safety of ALN-AT3SC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and AEs leading to study drug discontinuation. (time frame: Part A (SAD phase): through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112). 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 NCT02035605, which also lists 2 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 19 Dec 2020.