ObesityPhase 2NCT03171415
Evaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers
A Phase 2 study testing RZL-012 in people with Obesity and Weight Loss, run by Raziel Therapeutics Ltd. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity, Weight Loss, Overweight and Obesity
- What is being tested?
- RZL-012
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2017to 28 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult male subjects, 20-60 years old.
- Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.9.
- Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.
- Subjects with stable weight in the last 3 months by medical history.
- Not one of the following eating disorders by subject's declaration: anorexia nervosa, bulimia nervosa.
- Generally considered healthy according to medical history, physical examination, electrocardiogram (ECG) and laboratory evaluation with a special emphasis on metabolic parameters (fasting glucose concentration < 100 mg, normal blood pressure).
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- Subject is willing to refrain from sexual activity or agrees to use a double-barrier contraceptive device (e.g., condom and spermicide) for 4 weeks after treatment with RZL 012.
- Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
- Subjects must sign an informed consent indicating that they are aware of the investigational nature of the study.
Who cannot join
- Subjects weighing less than 75 kg.
- Subjects who have reduced/gained weight more than 5% of their current body weight in the last 3 months.
- Unable to tolerate subcutaneous injection.
- Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders, that in the opinion of the investigator put the subject at significant risk, are not eligible.
- Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) are not eligible.
- Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids are ineligible.
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- As a result of medical review, physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study.
- Medication use on regular basis.
- Positive drug and alcohol tests.
- Known sensitivity to components of the injection formulation.
- Prior wound, tattoo or infection in the treated area.
- Excessive growth of hair in the abdomen region.
- Claustrophobia or MRI incompatible device or implant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Obesity, Weight Loss, Overweight and Obesity
- Being tested
- RZL-012, Placebo
- Keywords
- Obesity, Overweight, Thermogenesis, Fat reduction
- Medical subject headings
- Obesity, Weight Loss, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RZL-012Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| RZL-012 | Experimental | A single-time injection, multiple subcutaneous injections of RZL-012 administered into 8-36 sites (0.1mL per site):
1. 40mg RZL-012 -administered at 8 sites
2. 80mg RZL-012 - administered at 16 sites
3. 120mg RZL-012 - administered at 24 sites
4. 180mg RZL-012 - administered at 36 sited Receives: Drug: RZL-012 |
| Placebo | Placebo comparator | A single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 28-168 days
Secondary outcomes (10)
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.
Measured: 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.
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.
Measured: 28-168 days
Changes in Fasting Blood Glucose From Baseline.
Changes from baseline in fasting blood glucose by visit, treatment, and cohort.
Measured: 56 days
Changes in Blood Lipid Profile From Baseline.
Changes from baseline in lipid profile by visit, treatment, and cohort.
Measured: 56 days
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Cmax values by cohort.
Measured: 1-2 days
Changes in Body Weight
Changes from baseline in body weight by visit, treatment, and cohort.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 28 days
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Tmax values by cohort.
Measured: 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2017
- Study start25 Jul 2017
- Primary completion28 Dec 2018
- Study completion28 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ObesityStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Raziel Therapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Spaulding Clinical Research LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03171415
- Sponsor's protocol ID
- RZL-012-P2aUS-001
- Status last verified
- Sep 2018
- First submitted
- 24 May 2017
- Last updated
- 21 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03171415
- Acronym / sponsor ID
- RZL-012-P2aUS-001
- Conditions
- Obesity, Weight Loss, Overweight and Obesity
- Keywords
- Obesity, Overweight, Thermogenesis, Fat reduction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Raziel Therapeutics Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Spaulding Clinical Research LLC
- Study start
- 25 Jul 2017 (actual)
- Primary completion
- 28 Dec 2018 (actual)
- Study completion
- 28 Dec 2018 (actual)
- First posted
- 31 May 2017 (actual)
- Results
- Posted 21 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| RZL-012 | Experimental | Drug: RZL-012A single-time injection, multiple subcutaneous injections of RZL-012 administered into 8-36 sites (0.1mL per site): 1. 40mg RZL-012 -administered at 8 sites 2. 80mg RZL-012 - administered at 16 sites 3. 120mg RZL-012 - administered at 24 sites 4. 180mg RZL-012 - administered at 36 sited |
| Placebo | Placebo comparator | Drug: PlaceboA single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site) |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Adult male subjects, 20-60 years old.
- Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.9.
- Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.
- Subjects with stable weight in the last 3 months by medical history.
- Not one of the following eating disorders by subject's declaration: anorexia nervosa, bulimia nervosa.
Key exclusion criteria (13 listed)
- Subjects weighing less than 75 kg.
- Subjects who have reduced/gained weight more than 5% of their current body weight in the last 3 months.
- Unable to tolerate subcutaneous injection.
- Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders, that in the opinion of the investigator put the subject at significant risk, are not eligible.
- Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) are not eligible.
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 |
|---|---|---|
| RZL-012Subject 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. | Drug | RZL-012 |
| PlaceboSubject 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. | Drug | Placebo |
Primary outcome
Safety: The Incidence of Treatment-related Adverse Events [AEs]
Time frame: 0-168 days
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.
Efficacy: A Significant Thermogenesis at the Injected Site.
Time frame: 28-168 days
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.
10 secondary outcomes
Duration of the Thermogenic Effect From Day 28.
Time frame: 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.
Time frame: 28-168 days
Changes in Fasting Blood Glucose From Baseline.
Time frame: 56 days
Changes in Blood Lipid Profile From Baseline.
Time frame: 56 days
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Time frame: 1-2 days
Changes in Body Weight
Time frame: 56 days
Changes in Waist to Hip Ratio [WHR]
Time frame: 56 days
Elucidation of the Histological Changes Account for the Thermogenic Effect.
Time frame: 56 days
Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling.
Time frame: 28 days
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Time frame: 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RZL-012 in people with Obesity and Weight Loss, run by Raziel Therapeutics Ltd. at 1 site in United States.
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 9 inclusion and 13 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 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety: The Incidence of Treatment-related Adverse Events [AEs] (time frame: 0-168 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Aug 2019.