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| Name | Class |
|---|---|
| Spaulding Clinical Research LLC | OTHER |
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Obesity is a direct result of food-intake in excess of body energy expenditure. Thus, induction of increased energy expenditure via the activation of thermogenesis at targeted anatomical sites can counterbalance obesity. This trial aims to study RZL-012, a novel compound, in treating obesity by activating thermogenesis in subcutaneous fat.
Obesity is a direct result of food-intake in excess of body energy expenditure. Therefore, a feasible approach to combat obesity is via energy-consuming activities, such as physical exercise. Unfortunately, our modern society is moving in the other direction, spending more time in immobilized positions, at work and at home. An alternative strategy for the induction of increased energy expenditure is via the activation of thermogenic cells that utilize fat to produce heat.RZL-012 is a novel molecule that enables de-novo generation of thermogenic tissue at favorable anatomical sites. As a result, the extra fat accumulated in obese persons will be turned into heat. This is a double blind, randomized, placebo controlled, dose escalation Phase 2a clinical trial for the evaluation of safety, efficacy and thermogenesis-induction of RZL-012 in overweight and obese volunteers. This trial aims to study the ability of RZL-012 in treating obesity via the induction of thermogenic foci in subcutaneous fat.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RZL-012 | Experimental | A single-time injection, multiple subcutaneous injections of RZL-012 administered into 8-36 sites (0.1mL per site):
|
|
| Placebo | Placebo Comparator | A single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RZL-012 | Drug | Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8-36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety: The Incidence of Treatment-related Adverse Events [AEs] | AEs will be assessed by significant clinical changes in safety parameter (e.g. vital signs, ECG, clinical laboratory evaluations)AEs incidence will be by body system, seriousness, severity and relation to study drug by cohort. | 0-168 days |
| Efficacy: A Significant Thermogenesis at the Injected Site. | Thermogenesis is measured by thermal imaging is non-invasive, non-radiating Infra-Red thermal camera that passively measures the emitting infra-red radiation of body surface. Difference in temperatures between the sites (treated - not treated) by visit treatment along with the change from baseline (net-delta) in these differences by cohort and overall. Significant thermogenesis is defined as net-delta ≥ 1. Outcome measure data table represents the number of subjects who demonstrated an increase that is higher than 1 celsius degree. | 28-168 days |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of the Thermogenic Effect From Day 28. | The duration of the thermogenic effect for subjects in the active arm with thermogenic effect (net-delta ≥ 1) by visit and cohort. | 28-168 days |
| Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spaulding Clinical | West Bend | Wisconsin | 53095 | United States |
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Study was designed to enroll 32 subjects. In practice, 33 subjects were enrolled into the study. In cohort 3, one subject that was injected with plcebo was lost to follow up 3 days following injection. Therefore, an additional subject was enrolled and injected with placebo but he also was lost to follow up, 7 days following injection.
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| ID | Title | Description |
|---|---|---|
| FG000 | RZL-012 Cohort 1 | A single-time injection, multiple subcutaneous injections of 40mg RZL-012 administered into 8 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8 (0.1mL per site) into the abdominal subcutaneous fat. |
| FG001 | RZL-012 Cohort 2 | A single-time injection, multiple subcutaneous injections of 80 mg RZL-012 administered into 16 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 16 (0.1mL per site) into the abdominal subcutaneous fat. |
| FG002 | RZL-012 Cohort 3 | A single-time injection, multiple subcutaneous injections of 120 mg RZL-012 administered into 24 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 24 (0.1mL per site) into the abdominal subcutaneous fat. |
| FG003 | RZL-012 Cohort 4 | A single-time injection, multiple subcutaneous injections of 180 mg RZL-012 administered into 36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 36 (0.1mL per site) into the abdominal subcutaneous fat. |
| FG004 | Placebo | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
20-60 years old, overweight and obese by BMI definition (27.5 < BMI ≤ 34.9), adult males.
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| ID | Title | Description |
|---|---|---|
| BG000 | RZL-012 Cohort 1 | A single-time injection, multiple subcutaneous injections of 40mg RZL-012 administered into 8 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8 (0.1mL per site) into the abdominal subcutaneous fat. |
| 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 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | AEs will be assessed by significant clinical changes in safety parameter (e.g. vital signs, ECG, clinical laboratory evaluations)AEs incidence will be by body system, seriousness, severity and relation to study drug by cohort. | 20-60 years old, overweight and obese by BMI definition (27.5 < BMI ≤ 34.9), adult males. | Posted | Number | participants | 0-168 days |
|
All reported adverse events were coded to a standard set of terms using MedDRA coding dictionary. Cohort 4 subjects were followed up for Adverse Events up to 168 days following injection.
None of the subjects was reported with SAEs. None of the subjects died during the study
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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 | RZL-012 Cohort 1 | A single-time injection, multiple subcutaneous injections of 40mg RZL-012 administered into 8 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8 (0.1mL per site) into the abdominal subcutaneous fat. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (20.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Racheli Gueta - Clinical Trials Manager | Raziel Therapeutics | 972-8-9126941 | racheli@raziel-therapy.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 4, 2018 | May 30, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 14, 2018 | May 30, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D015431 | Weight Loss |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| C000720429 | RZL-012 |
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This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
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Double Blind, Randomized, Placebo Controlled
| Placebo | Drug | Subject receive a single-time injection. Multiple injections of the Placebo are administered at 8-36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
|
Subcutaneous Fat Mass (SFM) ratio (treated sites / control sites) averaged over the MRI slices by visit, treatment and cohort and the change from baseline in SFM ratio (in % from the ratio at baseline) compared between the treatment arms. |
| 28-168 days |
| Changes in Fasting Blood Glucose From Baseline. | Changes from baseline in fasting blood glucose by visit, treatment, and cohort. | 56 days |
| Changes in Blood Lipid Profile From Baseline. | Changes from baseline in lipid profile by visit, treatment, and cohort. | 56 days |
| Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | Averaged Cmax values by cohort. | 1-2 days |
| Changes in Body Weight | Changes from baseline in body weight by visit, treatment, and cohort. | 56 days |
| Changes in Waist to Hip Ratio [WHR] | Changes from baseline in WHR by visit, treatment, and cohort. WHR is calculated by measurements of waist circumference and hip circumference. | 56 days |
| Elucidation of the Histological Changes Account for the Thermogenic Effect. | An abdominal subcutaneous adipose tissue biopsy will be taken from the injected side. Histology results will be assessed for 2 subjects who were injected with 120 mg RZL-012 and for one subject who was injected with placebo. | 56 days |
| Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | Changes from baseline in inflammatory markers and cytokines by visit, treatment, and cohort. Testing of inflammatory markers and cytokines will be conducted by blood sampling. | 28 days |
| Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | Averaged Tmax values by cohort. | 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours |
| RZL-012 Cohort 2 |
A single-time injection, multiple subcutaneous injections of 80mg RZL-012 administered into 16 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 16(0.1mL per site) into the abdominal subcutaneous fat. |
| BG002 | RZL-012 Cohort 3 | A single-time injection, multiple subcutaneous injections of 120mg RZL-012 administered into 24 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 24(0.1mL per site) into the abdominal subcutaneous fat. |
| BG003 | RZL-012 Cohort 4 | A single-time injection, multiple subcutaneous injections of 180mg RZL-012 administered into 36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 36(0.1mL per site) into the abdominal subcutaneous fat. |
| BG004 | Placebo | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site) Placebo: Subject receive a single-time injection. Multiple injections of the Placebo are administered at8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. |
| 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 |
|
| Region of Enrollment | Number | participants |
|
| RZL-012 Cohort 2 |
A single-time injection, multiple subcutaneous injections of 80mg RZL-012 administered into 16 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. |
| OG002 | RZL-012 Cohort 3 | A single-time injection, multiple subcutaneous injections of 120mg RZL-012 administered into 24 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. |
| OG003 | RZL-012 Cohort 4 | A single-time injection, multiple subcutaneous injections of 180mg RZL-012 administered into 36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. |
| OG004 | Placebo | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site) Placebo: Subject receive a single-time injection. Multiple injections of the Placebo are administered at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
|
|
| Primary | Efficacy: A Significant Thermogenesis at the Injected Site. | Thermogenesis is measured by thermal imaging is non-invasive, non-radiating Infra-Red thermal camera that passively measures the emitting infra-red radiation of body surface. Difference in temperatures between the sites (treated - not treated) by visit treatment along with the change from baseline (net-delta) in these differences by cohort and overall. Significant thermogenesis is defined as net-delta ≥ 1. Outcome measure data table represents the number of subjects who demonstrated an increase that is higher than 1 celsius degree. | Posted | Count of Participants | Participants | 28-168 days |
|
|
|
| Secondary | Duration of the Thermogenic Effect From Day 28. | The duration of the thermogenic effect for subjects in the active arm with thermogenic effect (net-delta ≥ 1) by visit and cohort. | Posted | Mean | Standard Deviation | days | 28-168 days |
|
|
|
| Secondary | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Subcutaneous Fat Mass (SFM) ratio (treated sites / control sites) averaged over the MRI slices by visit, treatment and cohort and the change from baseline in SFM ratio (in % from the ratio at baseline) compared between the treatment arms. | In cohort 4, one subjects was not analyzed due to MRI image quality (bubble) | Posted | Mean | Standard Deviation | percentage of SFM reduction | 28-168 days |
|
|
|
|
| Secondary | Changes in Fasting Blood Glucose From Baseline. | Changes from baseline in fasting blood glucose by visit, treatment, and cohort. | Posted | Mean | Standard Deviation | mg/dL | 56 days |
|
|
|
|
| Secondary | Changes in Blood Lipid Profile From Baseline. | Changes from baseline in lipid profile by visit, treatment, and cohort. | Posted | Mean | Standard Deviation | mg/dL | 56 days |
|
|
|
| Secondary | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | Averaged Cmax values by cohort. | Posted | Mean | Standard Deviation | ng/mL | 1-2 days |
|
|
|
| Secondary | Changes in Body Weight | Changes from baseline in body weight by visit, treatment, and cohort. | Posted | Mean | Standard Deviation | Kg | 56 days |
|
|
|
| Secondary | Changes in Waist to Hip Ratio [WHR] | Changes from baseline in WHR by visit, treatment, and cohort. WHR is calculated by measurements of waist circumference and hip circumference. | Posted | Mean | Standard Error | ratio | 56 days |
|
|
|
| Secondary | Elucidation of the Histological Changes Account for the Thermogenic Effect. | An abdominal subcutaneous adipose tissue biopsy will be taken from the injected side. Histology results will be assessed for 2 subjects who were injected with 120 mg RZL-012 and for one subject who was injected with placebo. | Biopsy was done only for 2 active and 1 placebo subjects in cohort 3. Biopsy was not done in subjects from cohorts 1,2 or 4. | Posted | Count of Participants | Participants | 56 days |
|
|
|
| Secondary | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | Changes from baseline in inflammatory markers and cytokines by visit, treatment, and cohort. Testing of inflammatory markers and cytokines will be conducted by blood sampling. | The study was designed in a way that inflammation marker will be measured only for active and placebo subjects from cohorts 2-4 | Posted | Mean | Standard Deviation | mg/dL | 28 days |
|
|
|
|
| Secondary | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | Averaged Tmax values by cohort. | Posted | Mean | Standard Deviation | Hour | 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| EG001 | RZL-012 Cohort 2 | A single-time injection, multiple subcutaneous injections of 80 mg RZL-012 administered into 16 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 16 (0.1mL per site) into the abdominal subcutaneous fat. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | RZL-012 Cohort 3 | A single-time injection, multiple subcutaneous injections of 120 mg RZL-012 administered into 24 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 24 (0.1mL per site) into the abdominal subcutaneous fat. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG003 | RZL-012 Cohort 4 | A single-time injection, multiple subcutaneous injections of 180 mg RZL-012 administered into 36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 36 (0.1mL per site) into the abdominal subcutaneous fat. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG004 | Placebo | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. | 0 | 9 | 0 | 9 | 9 | 9 |
| ear pain | Ear and labyrinth disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| ear swelling | Ear and labyrinth disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Otorrhoea | Ear and labyrinth disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Energy increased | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| fatigue | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site discolouration | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site Erythema | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site hemmorhage | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site mass | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site nodule | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site Edema | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site rash | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Injection site warmth | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Medical device reaction | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Non cardiac chest pain | General disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (20.0) | Non-systematic Assessment |
|
| Electrocardiac QT prolonged | Investigations | MedDRA (20.0) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Orpharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Non-systematic Assessment |
|
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| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001836 | Body Weight Changes |
| Day 56 |
|
| Day 84 |
|
| Day 112 |
|
| Day 140 |
|
| Day 168 |
|
| Day 56 |
|
| Day 84 |
|
| Day 112 |
|
| Day 140 |
|
| Day 168 |
|
| Kruskal-Wallis |
| <0.05 |
| Superiority |
| The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups | Kruskal-Wallis | <0.05 | Superiority |
| The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups | Kruskal-Wallis | <0.05 | Superiority |
| Day 56 |
|
| Other |
| t-test, 2 sided | >0.05 | Other |
| t-test, 2 sided | >0.05 | Other |
| Cholesterol Day 56 |
|
| HDL Day -1 |
|
| HDL Day 56 |
|
| LDL Day -1 |
|
| LDL Day 56 |
|
| Triglycerides Day -1 |
|
| Triglycerides Day 56 |
|
| Weight Day 56 |
|
| Waist to hip ratio Day 56 |
|
| CRP Day 28 (mg/dL) |
|