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| Name | Class |
|---|---|
| Herlev Hospital | OTHER |
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ATLAS-IT-04 is a two part, single arm study designed to determine the safety and effectiveness of LTX-315 to induce T-cell infiltration prior to TIL expansion in patients with soft tissue sarcoma. Following intratumoural injection of LTX-315 to a selected lesion, the lesion will be extracted for T-cell culture, expansion and infusion.
Patients with advanced/metastatic tumours who have received at least one approved standard of care treatment will be recruited. All patients must have at least two lesions, one that can injected with LTX-315 and another that can used to assess response. In the first part of the study, LTX-315 will be administered intratumorally on 4-6 dosing days over a 2-4 week period to an index lesion which will be biopsied or removed after treatment for T-cell expansion. The second part will involve culturing and expanding T-cells for infusion of tumour infiltrating lymphocytes (TILs) following an induction regimen. The safety and efficacy of the LTX-315 and TIL treatment will be assessed. Patients will be followed up for 15 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LTX-315 plus TIL infusion | Experimental | LTX-315 intratumoural injection, TILs expansion and infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LTX-315 and TILs | Combination Product | Intratumoural injection of LTX-315 and infusion of TILs |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Total T-cell Level in Tumour Tissues From Baseline (Step 1, Week 1, Day 1) to End of Step 1 (Step 1, Week 3-5) | The total T-cell level was measured at baseline and end of Step 1. Change from baseline was listed as absolute change. Data cannot be presented on subject-level and are therefore presented as the arithmetic mean value for the factor increase (+) or decrease (-) in number of cells/mm2 from baseline to end of Step 1. | 15 to 42 days |
| Adverse Events (AE) Related to LTX-315 or to the Combination of LTX-315 and Adoptive T-cell Therapy From Baseline (Step 1, Week 1, Day 1) to End of Treatment (EoT) (Step 2, Week 7) | AEs were events occurring during or after administration of the IMP. AEs were coded using MedDRA version 21.1 and were classified by System Organ Class (SOC), Preferred Term (PT) and Lowest Level Term (LLT). Adverse events related to LTX-315 were events where causality to LTX-315 was marked on the adverse events page. Adverse events related to the combination of LTX-315 and adoptive T-cell therapy were events where both causality to LTX-315 and at least one of the other IMPs (TILs, Sendoxan®, Fludara® and Proleukin®) were marked on the adverse event page. | Up to 133 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in CD3+CD8+ T Cell Density in Non-injected Tumour Tissues From Baseline (Step 1, Week 1, Day 1) to EoT (Step 2, Week 7) | The change is described as factor change in CD8+ cells/mm2. | Up to 133 days |
| Total Number of CD3+CD8+ T-cells in TIL Infusion Product |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells | Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells antigen specificity assessed by enzyme-linked immuno-spot assay (ELISPOT) and flowcytometry analysis of cytokines including interferon gamma (IFNγ) and tumour necrosis factor alpha (TNF⍺) | Up to 15 months |
Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Inge Marie Svane, MD | Herlev Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Herlev Hospital | Copenhagen | DK-2730 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38125722 | Derived | Nielsen M, Monberg T, Sundvold V, Albieri B, Hovgaard D, Petersen MM, Krarup-Hansen A, Met O, Camilio K, Clancy T, Stratford R, Sveinbjornsson B, Rekdal O, Junker N, Svane IM. LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients with metastatic soft tissue sarcoma. Oncoimmunology. 2023 Dec 7;13(1):2290900. doi: 10.1080/2162402X.2023.2290900. eCollection 2024. |
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| ID | Title | Description |
|---|---|---|
| FG000 | LTX-315 plus TIL infusion | LTX-315 intratumoural injection, TILs expansion and infusion. LTX-315 and TILs: Intratumoural injection of LTX-315 and infusion of TILs |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | LTX-315 Plus TIL Infusion | LTX-315 intratumoural injection, TILs expansion and infusion. LTX-315 and TILs: Intratumoural injection of LTX-315 and infusion of TILs |
| 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 | Change in Total T-cell Level in Tumour Tissues From Baseline (Step 1, Week 1, Day 1) to End of Step 1 (Step 1, Week 3-5) | The total T-cell level was measured at baseline and end of Step 1. Change from baseline was listed as absolute change. Data cannot be presented on subject-level and are therefore presented as the arithmetic mean value for the factor increase (+) or decrease (-) in number of cells/mm2 from baseline to end of Step 1. | For 1 subject evaluation was not possible due to complete necrosis of the injected lesion | Posted | Mean | Full Range | factor change in cells/mm2 | 15 to 42 days |
|
AEs were collected from the day the subject signed the informed consent and for up to 15 months.
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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 | LTX-315 plus TIL infusion | LTX-315 intratumoural injection, TILs expansion and infusion. LTX-315 and TILs: Intratumoural injection of LTX-315 and infusion of TILs |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director Scientific Research Baldur Sweinbjornsson | Lytix Biopharma AS | +47 413 44 682 | Baldur.Sveinbjornsson@lytixbiopharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 31, 2020 | Jan 17, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 18, 2022 | Jan 17, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012509 | Sarcoma |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000609766 | LTX-315 |
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LTX-315 and TILs
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The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs. |
| 41 to 49 days between Step 1 and Step 2 |
| % CD3+CD8+ T-cells of Total CD3+ in TIL Infusion Product | The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs. | 41 to 49 days between Step 1 and Step 2 |
| Objective Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | EoT (Step 2, Week 7) and up to 15 months after EoT. |
| Clinical Benefit Rate | The clinical benefit rate (CBR) was defined as proportion of subjects who according to RECIST 1.1 had achieved complete response, partial response or stable disease at EoT (Step 2, Week 7) and up to 15 months after EoT. CBR was evaluated at Step 2, Week 7 and Week 13. | Up to 15 months |
| Best Overall Tumour Response Rate | Best overall tumour response rate (BOR) was defined in the CSP as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). | Assessed at Visit 25 (Step 2, Week 7, Day 42) |
| Progression Free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Days from screening (Baseline) until date of progressive disease or up to 15 months after EoT. |
| Changes in Immunological Parameters From Baseline (Step 1, Week 1, Day 1) to 15 Months After EoT | Systemic immune effect of the treatment was assessed by sequencing the TCR repertoire in the peripheral blood mononuclear cells (PBMCs), the TIL product and the biopsies. The outcome of this endpoint is described as the number of subjects for whom a systemic immune effect (in terms of expansion of a significant number of T-cell clones in the blood) was observed. | Up to 15 months |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Adverse Events (AE) Related to LTX-315 or to the Combination of LTX-315 and Adoptive T-cell Therapy From Baseline (Step 1, Week 1, Day 1) to End of Treatment (EoT) (Step 2, Week 7) | AEs were events occurring during or after administration of the IMP. AEs were coded using MedDRA version 21.1 and were classified by System Organ Class (SOC), Preferred Term (PT) and Lowest Level Term (LLT). Adverse events related to LTX-315 were events where causality to LTX-315 was marked on the adverse events page. Adverse events related to the combination of LTX-315 and adoptive T-cell therapy were events where both causality to LTX-315 and at least one of the other IMPs (TILs, Sendoxan®, Fludara® and Proleukin®) were marked on the adverse event page. | AEs related to LTX-315 treatment were evaluated for the 6 subjects completing Step 1. AEs related to LTX-315 treatment in combination with adoptive T-cell therapy were evaluated for the 4 subjects completing Step 2. | Posted | Number | events | Up to 133 days |
|
|
|
| Secondary | Change in CD3+CD8+ T Cell Density in Non-injected Tumour Tissues From Baseline (Step 1, Week 1, Day 1) to EoT (Step 2, Week 7) | The change is described as factor change in CD8+ cells/mm2. | The change in CD3+CD8+ T-cells from baseline to end of Step 2 could only be evaluated for 1 subject. | Posted | Mean | Full Range | factor change in CD8+ cells/mm2 | Up to 133 days |
|
|
|
| Secondary | Total Number of CD3+CD8+ T-cells in TIL Infusion Product | The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs. | TIL infusion product was evaluated for the 4 subjects for whom it was possible to grow TILs. For 2 subjects it was not possible to meet the criteria of 4x10^7 cells as described in the IMPD. | Posted | Mean | Full Range | million CD8+ T-cells | 41 to 49 days between Step 1 and Step 2 |
|
|
|
| Secondary | % CD3+CD8+ T-cells of Total CD3+ in TIL Infusion Product | The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs. | The composition of the TIL infusion product was evaluated for the 4 subjects for whom it was possible to grow TILs. For 2 subjects it was not possible to meet the criteria of 4x10^7 cells as described in the IMPD. | Posted | Mean | Full Range | %CD8+ of total CD3+ T-cells in TILs | 41 to 49 days between Step 1 and Step 2 |
|
|
|
| Secondary | Objective Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | ORR was evaluated for the 4 subjects who progressed to Step 2. | Posted | Number | participants | EoT (Step 2, Week 7) and up to 15 months after EoT. |
|
|
|
| Secondary | Clinical Benefit Rate | The clinical benefit rate (CBR) was defined as proportion of subjects who according to RECIST 1.1 had achieved complete response, partial response or stable disease at EoT (Step 2, Week 7) and up to 15 months after EoT. CBR was evaluated at Step 2, Week 7 and Week 13. | The endpoint was evaluated for the 4 subjects who progressed to Step 2. | Posted | Number | participants | Up to 15 months |
|
|
|
| Secondary | Best Overall Tumour Response Rate | Best overall tumour response rate (BOR) was defined in the CSP as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). | Evaluated for the 4 subjects who progressed to Step 2. | Posted | Count of Participants | Participants | Assessed at Visit 25 (Step 2, Week 7, Day 42) |
|
|
|
| Secondary | Progression Free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Endpoint evaluated for the 4 subjects who progressed to Step 2. | Posted | Mean | Full Range | days | Days from screening (Baseline) until date of progressive disease or up to 15 months after EoT. |
|
|
|
| Other Pre-specified | Number of Participants With Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells | Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells antigen specificity assessed by enzyme-linked immuno-spot assay (ELISPOT) and flowcytometry analysis of cytokines including interferon gamma (IFNγ) and tumour necrosis factor alpha (TNF⍺) | Endpoint evaluated for the 4 subjects who progressed to Step 2. | Posted | Number | participants | Up to 15 months |
|
|
|
| Other Pre-specified | Changes in Immunological Parameters From Baseline (Step 1, Week 1, Day 1) to 15 Months After EoT | Systemic immune effect of the treatment was assessed by sequencing the TCR repertoire in the peripheral blood mononuclear cells (PBMCs), the TIL product and the biopsies. The outcome of this endpoint is described as the number of subjects for whom a systemic immune effect (in terms of expansion of a significant number of T-cell clones in the blood) was observed. | This endpoint was evaluated for 2 subjects only. | Posted | Number | participants | Up to 15 months |
|
|
|
| 0 |
| 6 |
| 3 |
| 6 |
| 6 |
| 6 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Fascial rupture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Hypoglycaemia | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Gastric disorder | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Localised oedema | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Oedema | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Oral fungal infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Blood alkaline phosphatase decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Blood magnesium decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Blood potassium decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Blood sodium decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 21.1 | Systematic Assessment |
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| International normalised ratio increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Transaminases decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
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| Facial paresis | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
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The PI has the right to publish the study results in scientific or other journals, or to present the study results at professional conferences or other meetings. The PI may use the study results solely for internal research and/or educational purposes and shall not externally publish or present any such results until the earlier of (i) the date of the first study results publication, agreed by the parties and (ii) the end of the 18 month period following the completion of the study.
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