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SIG-001 programme terminated
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| Name | Class |
|---|---|
| Sigilon Therapeutics, Inc. | INDUSTRY |
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SIG-001-121 is a first-in-human (FIH), phase 1/2, multi-centre, open-label, dose escalation study to assess the safety, tolerability, and preliminary efficacy of SIG-001 in adults with severe or moderately severe haemophilia A without inhibitors. Up to three dose cohorts (3 patients each) are planned. Cohort expansions (up to 3 additional patients) may be triggered to collect additional information about safety and efficacy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SIG-001 | Experimental | Participants received a single dose of 50 milliliter (mL), 78.5 mL and 133 mL of SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce B-Domain Deleted Human Factor VIII (BDD-hFVIII) producing Spheres] administered laparoscopically into the peritoneal cavity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SIG-001 | Combination Product | Laparoscopic administration of SIG-001 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Participants with at least one TEAEs are reported. A summary of other nonserious adverse events (AEs), and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section. | Baseline Up to 115 Weeks |
| Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs) | Number of Participants with at least one serious TEAEs are reported. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | Baseline Up to 115 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay | Development of FVIII inhibitors is measured using the Nijmegen Bethesda inhibitor assay. The assay measures inhibitors to BDD-FVIII and also other forms of FVIII in the plasma, although rFVIII-BDD was used as a calibrator. | Baseline Up to 115 Weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Study Site | Indianapolis | Indiana | 46260 | United States | ||
| Clinical Study Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Participants received a single dose of 50 milliliter (mL) SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce B-Domain Deleted Human Factor VIII (BDD-hFVIII) producing Spheres] administered laparoscopically into the peritoneal cavity. |
| FG001 | Cohort 2 | Participants received a single dose of 78.5 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. |
| FG002 | Cohort 3 | Participants received a single dose of 133 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Participants received a single dose of 50 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce B-Domain Deleted Human Factor VIII (BDD-hFVIII) producing Spheres] administered laparoscopically into the peritoneal cavity. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Number of Participants with at least one TEAEs are reported. A summary of other nonserious adverse events (AEs), and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section. | All participants who received at least one dose of study drug and have at least one postdose safety assessment. | Posted | Number | Participants | Baseline Up to 115 Weeks |
|
Baseline Up to 115 Weeks
All participants who received at least one dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | Participants received a single dose of 50 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce B-Domain Deleted Human Factor VIII (BDD-hFVIII) producing Spheres] administered laparoscopically into the peritoneal cavity. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Factor viii inhibition | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 4, 2021 | Apr 8, 2024 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays |
The change from baseline in FVIII activity, as measured by one-stage and chromogenic assays) is summarized. |
| Baseline Up to 115 Weeks |
| Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration | The annualized number of bleeds per participant (annualized bleeding rate) is calculated as the number of bleeding events divided by length of time on study product follow-up, in years. The duration of assessment for this outcome measure was two years and three months, and Year 3 includes only the three-month part of this study period. | Time Frame: Pre-infusion (bleeding events in 12 months prior to sphere placement), 1 year, 2 year and 3-year post-infusion (post sphere placement) from SIG-001 administration annualized up to 115 Weeks. |
| Total Number of Replacement FVIII Therapies | Number of doses after prophylaxis discontinued is reported. | Baseline Up to 115 weeks |
| Boston |
| Massachusetts |
| 02116 |
| United States |
| Clinical Study Site | Seattle | Washington | 98104 | United States |
| Clinical Study Site | London | United Kingdom |
| Clinical Study Site | Manchester | United Kingdom |
| Clinical Study Site | Southampton | United Kingdom |
| Cohort 2 |
Participants received a single dose of 78.5 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. |
| BG002 | Cohort 3 | Participants received a single dose of 133 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. |
| BG003 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Number | participants |
|
| Cohort 2 |
Participants received a single dose of 78.5 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. |
| OG002 | Cohort 3 | Participants received a single dose of 133 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. |
|
|
| Primary | Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs) | Number of Participants with at least one serious TEAEs are reported. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | All participants who received at least one dose of study drug and have at least one postdose safety assessment. | Posted | Number | participants | Baseline Up to 115 Weeks |
|
|
|
| Secondary | Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay | Development of FVIII inhibitors is measured using the Nijmegen Bethesda inhibitor assay. The assay measures inhibitors to BDD-FVIII and also other forms of FVIII in the plasma, although rFVIII-BDD was used as a calibrator. | All participants who received at least one dose of study drug and had at least one postbaseline efficacy assessment. | Posted | Number | participants | Baseline Up to 115 Weeks |
|
|
|
| Secondary | Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays | The change from baseline in FVIII activity, as measured by one-stage and chromogenic assays) is summarized. | All participants who received at least one dose of study drug and had at least one postbaseline efficacy assessment. | Posted | Mean | Standard Deviation | International Unit/deciliter (IU/dL) | Baseline Up to 115 Weeks |
|
|
|
| Secondary | Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration | The annualized number of bleeds per participant (annualized bleeding rate) is calculated as the number of bleeding events divided by length of time on study product follow-up, in years. The duration of assessment for this outcome measure was two years and three months, and Year 3 includes only the three-month part of this study period. | All participants who received at least one dose of study drug and had at least one postbaseline efficacy assessment. | Posted | Number | Bleeding events per year | Time Frame: Pre-infusion (bleeding events in 12 months prior to sphere placement), 1 year, 2 year and 3-year post-infusion (post sphere placement) from SIG-001 administration annualized up to 115 Weeks. |
|
|
|
| Secondary | Total Number of Replacement FVIII Therapies | Number of doses after prophylaxis discontinued is reported. | All participants who received at least one dose of study drug and had at least one postbaseline efficacy assessment. | Posted | Number | Number of doses | Baseline Up to 115 weeks |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Cohort 2 | Participants received a single dose of 78.5 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | Cohort 3 | Participants received a single dose of 133 mL SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII producing Spheres] administered laparoscopically into the peritoneal cavity. | 0 | 1 | 1 | 1 | 1 | 1 |
| Drug ineffective | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anti factor viii antibody increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Faeces hard | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Axillary pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vaccination site pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Covid-19 | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Limb crushing injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Vaccination complication | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Cullen's sign | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haemorrhage subcutaneous | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Umbilical erythema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
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| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| One-stage |
|
| Title | Measurements |
|---|---|
|
| Year 2 |
|
| Year 3 |
|