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| ID | Type | Description | Link |
|---|---|---|---|
| 2U44AI095172-08 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Covance | INDUSTRY |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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This first-in-human study will evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of the HIV entry inhibitor CPT31 (cholesterol-PIE12-2-trimer) in healthy adults. This is a randomized, placebo-controlled, double-blind, single ascending dose study.
This is a single subcutaneous (SC) dose study. Doses will be administered in an escalating manner following satisfactory review by a Protocol Safety Review Team (PSRT) of the safety, tolerability and pharmacokinetic (PK) data through Day 6 from the lower dose levels. 32 healthy subjects will be studied in 4 groups (Groups A1 to A4).
This study will comprise a placebo-controlled, double-blind, single-dose, sequential-group design in healthy subjects. Each subject will participate in 1 treatment period and reside in the Clinical Research Unit (CRU) from Day -1 through Day 6. It is planned for 6 subjects per dose level group to receive SC CPT31 and 2 subjects to receive matching placebo. Each group will be divided into 2 cohorts, with each cohort being dosed 72 hours apart. Sentinel dosing will take place in the first cohort, which will comprise 2 subjects, with 1 subject receiving CPT31 and 1 subject receiving placebo. The second cohort will comprise 6 subjects, with 5 subjects receiving CPT31 and 1 subject receiving placebo. Blood samples for PK analysis and assessment of immunogenicity will be collected predose and up to 5 days postdose, with an additional immunogenicity sample taken at the Follow-up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) and 2 subjects receiving matching placebo SC injection |
|
| Cohort 2 | Experimental | 6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) and 2 subjects receiving matching placebo SC injection |
|
| Cohort 3 | Experimental | 6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) and 2 subjects receiving matching placebo SC injection |
|
| Cohort 4 | Experimental | 6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) and 2 subjects receiving matching placebo SC injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CPT31 | Drug | CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
|
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Number of subjects experiencing serious adverse events (SAEs) | Check-in (Day -1) through Follow-up (Day 28-30) |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | maximum observed plasma concentration (ng/mL) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Tmax |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alan L Mueller, PhD | Navigen, Inc. | Study Director |
| Hugh A Coleman, DO | Covance | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit Inc. | Daytona Beach | Florida | 32117 | United States |
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32 subjects met inclusion criteria and were randomized to treatment.
Participants were recruited at a single site in the United States between 16 November 2020 (date of first informed consent) and 29 April 2021 (date of last subject's last assessment).
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 0.01 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| FG001 | Cohort 2 0.04 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| FG002 | Cohort 3 0.12 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| FG003 | Cohort 4 0.24 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| FG004 | Placebo | 8 subjects receiving a single subcutaneous placebo injection |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 0.10 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| BG001 | Cohort 2 0.04 mg/kg CPT31 |
| 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 | Adverse Events | Number of subjects experiencing serious adverse events (SAEs) | The safety population included all subjects who received at least 1 dose of study treatment (CPT31 or placebo). | Posted | Number | participants experiencing adverse events | Check-in (Day -1) through Follow-up (Day 28-30) |
|
30 days
Subjects will be observed for any signs or symptoms and asked about their condition by open questioning. Subjects will also be encouraged to spontaneously report adverse events (AEs) occurring at any other time during the study. All nonserious AEs, whether reported by the subject voluntarily or upon questioning, or noted on physical examination, will be recorded from initiation of study drug until study end. Serious AEs will be recorded from signing the informed consent form until study end.
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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 0.01 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection Site Erythema | General disorders | DAIDS Table v2.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alan L. Mueller, VP Research | Navigen, Inc. | 801-243-9703 | amueller@nvgn.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 | Jul 27, 2020 | Aug 30, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 13, 2020 | Aug 30, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| Placebo | Drug | matching placebo |
|
time of maximum observed plasma concentration (h)
| Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| T1/2 | apparent plasma terminal elimination half-life (h) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Area Under the Concentration Curve (AUC) 0-∞ | area under the concentration versus time curve (AUC) from time zero to infinity (h*ng/mL) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| AUC0-tlast | area under the concentration versus time curve (AUC) from time zero to time of the last quantifiable concentration (h*ng/mL) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Total Plasma Clearance (CL/F) | apparent total plasma clearance (L/h/kg) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Vz/F | apparent volume of distribution (L/kg) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Ae | amount of drug excreted in the urine (ng/mL) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Fe | percentage of dose excreted unchanged in the urine (%) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Renal Clearance (CLR) | renal clearance (L/h/kg) | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
| Immunogenicity | Number of subjects with measurable levels of anti-CPT31 antibodies in serum | Pre-dose on Day 1 through Follow-up (Day 28-30) |
6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| BG002 | Cohort 3 0.12 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| BG003 | Cohort 4 0.24 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| BG004 | Placebo | 8 subjects receiving a single subcutaneous placebo injection |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | body mass index (kg/m2) | Mean | Standard Deviation | kg/m^2 |
|
| OG002 | Cohort 3 0.12 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| OG003 | Cohort 4 0.24 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer |
| OG004 | Placebo | 8 subjects receiving a single subcutaneous placebo injection |
|
|
| Secondary | Cmax | maximum observed plasma concentration (ng/mL) | The pharmacokinetic (PK) population included all subjects who received at least 1 dose of CPT31 and had evaluable PK data. | Posted | Mean | Full Range | ng/mL | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
|
|
|
|
| Secondary | Tmax | time of maximum observed plasma concentration (h) | The PK population included all subjects who received at least 1 dose of CPT31 and had evaluable PK data. | Posted | Median | Full Range | Hours post administration | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
|
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|
|
| Secondary | T1/2 | apparent plasma terminal elimination half-life (h) | Insufficient data for Cohorts 1&2. No t1/2 estimate possible for 3 subjects in Cohorts 1&2, and 1 in Cohort 4 as a reliable regression could not be fitted to the data. Per SAP: terminal elimination rate constant (λz) will only be calculated when a reliable estimate is obtained using ≥3 data points, and adjusted coefficient for determination of exponential fit (R2-adj) of the regression line is ≥0.7. Parameters requiring λz will only be calculated if R2-adj value of the regression is ≥0.7. | Posted | Mean | Full Range | Hours post administration | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
|
|
|
|
| Secondary | Area Under the Concentration Curve (AUC) 0-∞ | area under the concentration versus time curve (AUC) from time zero to infinity (h*ng/mL) | Insufficient data for Cohorts 1&2. No (AUC)0-∞ estimate possible for 3 subjects in Cohorts 1&2, and 1 in Cohort 4 as a reliable regression could not be fitted to the data. Per SAP: terminal elimination rate constant (λz) will only be calculated when a reliable estimate is obtained using ≥3 data points, and adjusted coefficient for determination of exponential fit (R2-adj) of the regression line is ≥0.7. Parameters requiring λz will only be calculated if R2-adj value of the regression is ≥0.7. | Posted | Mean | Full Range | h*ng/mL | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
|
|
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| Secondary | AUC0-tlast | area under the concentration versus time curve (AUC) from time zero to time of the last quantifiable concentration (h*ng/mL) | The PK population included all subjects who received at least 1 dose of CPT31 and had evaluable PK data. | Posted | Mean | Full Range | h*ng/mL | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
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|
|
| Secondary | Total Plasma Clearance (CL/F) | apparent total plasma clearance (L/h/kg) | Insufficient data for Cohorts 1&2. No CL/F estimate possible for 3 subjects in Cohorts 1&2, and 1 in Cohort 4 as a reliable regression could not be fitted to the data. Per SAP: terminal elimination rate constant (λz) will only be calculated when a reliable estimate is obtained using ≥3 data points, and adjusted coefficient for determination of exponential fit (R2-adj) of the regression line is ≥0.7. Parameters requiring λz will only be calculated if R2-adj value of the regression is ≥0.7 | Posted | Mean | Full Range | L/h/kg | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
|
|
|
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| Secondary | Vz/F | apparent volume of distribution (L/kg) | Insufficient data for Cohorts 1&2. No Vz/F estimate possible for 3 subjects in Cohorts 1&2, and 1 in Cohort 4 as a reliable regression could not be fitted to the data. Per SAP: terminal elimination rate constant (λz) will only be calculated when a reliable estimate is obtained using ≥3 data points, and adjusted coefficient for determination of exponential fit (R2-adj) of the regression line is ≥0.7. Parameters requiring λz will only be calculated if R2-adj value of the regression is ≥0.7 | Posted | Mean | Full Range | L/kg | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
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| Secondary | Ae | amount of drug excreted in the urine (ng/mL) | Concentrations for all subjects in Cohorts 1-3 were below the limit of quantitation. Urine was not collected for Cohort 4. | Posted | Mean | Full Range | ng/mL | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
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| Secondary | Fe | percentage of dose excreted unchanged in the urine (%) | Concentrations for all subjects in Cohorts 1-3 were below the limit of quantitation. Urine was not collected for Cohort 4. | Posted | Mean | Full Range | percentage of drug excreted unchanged | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
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| Secondary | Renal Clearance (CLR) | renal clearance (L/h/kg) | Concentrations for all subjects in Cohorts 1-3 were below the limit of quantitation. Urine was not collected for Cohort 4. | Posted | Mean | Standard Deviation | L/h/kg | Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h) |
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| Secondary | Immunogenicity | Number of subjects with measurable levels of anti-CPT31 antibodies in serum | Posted | Count of Participants | Participants | Pre-dose on Day 1 through Follow-up (Day 28-30) |
|
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Cohort 2 0.04 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Cohort 3 0.12 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | Cohort 4 0.24 mg/kg CPT31 | 6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) CPT31: CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer | 0 | 6 | 0 | 6 | 5 | 6 |
| EG004 | Placebo | 8 subjects receiving a single subcutaneous placebo injection | 0 | 8 | 0 | 8 | 1 | 8 |
| Injection Site Pain | General disorders | DAIDS Table v2.1 | Systematic Assessment |
|
| Injection Site Induration | General disorders | DAIDS Table v2.1 | Systematic Assessment |
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| Injection Site Pruritis | General disorders | DAIDS Table v2.1 | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | DAIDS Table v2.1 | Systematic Assessment |
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| Dry Skin | Skin and subcutaneous tissue disorders | DAIDS Table v2.1 | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | DAIDS Table v2.1 | Systematic Assessment |
|
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| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |