Trial Outcomes & Findings for Efficacy and Safety of RZL-012 on Submental Fat Reduction (NCT NCT04867434)

Last Updated: 2023-09-28

Results Overview

To determine the efficacy of RZL-012 versus placebo on submental fat (SMF) reduction measured on Day 84 versus baseline using the Clinician Chin Assessment Tool (C-CAT). The CAT is composed of 5 points where 0 represents no fat and 4 represent very noticeable bulge and fat that extends beyond the neck

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

151 participants

Primary outcome timeframe

84 days

Results posted on

2023-09-28

Participant Flow

Participant milestones

Participant milestones
Measure	RZL-012 50mg/ml Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo
Overall Study STARTED	50	53	48
Overall Study COMPLETED	50	49	47
Overall Study NOT COMPLETED	0	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of RZL-012 on Submental Fat Reduction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RZL-012 50mg/ml n=50 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml n=53 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo n=48 Participants Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo	Total n=151 Participants Total of all reporting groups
Age, Continuous	44.6 years STANDARD_DEVIATION 9.7 • n=5 Participants	42.8 years STANDARD_DEVIATION 10.7 • n=7 Participants	41.6 years STANDARD_DEVIATION 10.8 • n=5 Participants	43 years STANDARD_DEVIATION 10.6 • n=4 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	45 Participants n=7 Participants	34 Participants n=5 Participants	121 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants	30 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black Or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	37 Participants n=5 Participants	39 Participants n=7 Participants	36 Participants n=5 Participants	112 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian Or Alaska Native	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian Or Other Pacific	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Not reported or Unknown	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	50 Participants n=5 Participants	53 Participants n=7 Participants	48 Participants n=5 Participants	151 Participants n=4 Participants

PRIMARY outcome

Timeframe: 84 days

Population: The proportion of subjects who have at least a 1-grade improvement in the C-CAT on Day 84 versus baseline will be calculated for the placebo group and the RZL-012 high-dose group along with 95% Confidence interval for proportion

Outcome measures

Outcome measures
Measure	RZL-012 50mg/ml n=50 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml n=53 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo n=48 Participants Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo
Efficacy -Proportion of Subjects With at Least a 1-grade Improvement in the C-CAT Scale at Day 84	43 participants	39 participants	27 participants

SECONDARY outcome

Timeframe: 84 days

Population: \- The Chi-Square test will be applied to test the statistical difference between the placebo group and each of the RZL-012 dose groups in the responder rate at Day 84 where responder rate is defined as the percentage of subject achieving at least a 1-grade improvement from baseline in S-CAT

To determine the efficacy of RZL-012 versus placebo on submental fat (SMF) reduction measured on Day 84 versus baseline using the Subject Chin Assessment Tool (S-CAT). The CAT is composed of 5 points where 0 represents no fat and 4 represent very noticeable bulge and fat that extends beyond the neck

Outcome measures

Outcome measures
Measure	RZL-012 50mg/ml n=50 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml n=53 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo n=48 Participants Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo
Efficacy - the Proportion of Subjects With at Least 1-grade Improvement in Subject Chin Assessment Tool (S-CAT)	43 participants	42 participants	30 participants

SECONDARY outcome

Timeframe: 84 days

Population: The Paired T-test for two means (paired observations) will be applied for testing the statistical significance of the change and percentage of change from baseline at Day 84 in SMF thickness measured with caliper and in SMF volume by MRI within each study group

Percent reduction from baseline in submental fat volume , as measured with MRI in RZL-012 treated subjects vs. placebo treated subjects on Day 84 following injection vs. baseline.

Outcome measures

Outcome measures
Measure	RZL-012 50mg/ml n=41 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml n=44 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo n=45 Participants Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo
Efficacy - Relative Change in Submental Fat Volume on Day 84 vs. Baseline	-14.92 percentage of volume reduction Standard Deviation 9.98	-8.34 percentage of volume reduction Standard Deviation 11.72	1.45 percentage of volume reduction Standard Deviation 8.68

SECONDARY outcome

Timeframe: 84 days

Population: The incidence of AEs will be presented by treatment. Descriptive statistics will be calculated for quantitative data and frequency counts and percentages will be provided for categorical data. All reported AEs are treatment related

To evaluate the safety of RZL-012 subcutaneous injections in the submental area, relative to placebo, as assessed by spontaneous adverse event reports and post injection evaluation of treatment area. Treatment area evaluations including, but not limited to evaluation of edema, bruising, dysphasia, dysphonia, erythema, dyspigmentation, induration, numbness, pain, paresthesia, and pruritus. The number of subjects with treatment-related adverse events will be compared within each treatment group, as assessed by CTCAE v4.0.

Outcome measures

Outcome measures
Measure	RZL-012 50mg/ml n=50 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml n=53 Participants Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo n=48 Participants Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo
Safety - Adverse Events Follow up Injection site hypersensitivity	2 participants	1 participants	0 participants
Safety - Adverse Events Follow up Injection site induration	7 participants	7 participants	0 participants
Safety - Adverse Events Follow up Injection site movement impairement	3 participants	1 participants	0 participants
Safety - Adverse Events Follow up Dizziness	2 participants	2 participants	0 participants
Safety - Adverse Events Follow up Headache	3 participants	4 participants	3 participants
Safety - Adverse Events Follow up Facial paralysis	3 participants	1 participants	0 participants
Safety - Adverse Events Follow up Hypoesthesia	3 participants	0 participants	0 participants
Safety - Adverse Events Follow up Dysphonia	2 participants	2 participants	0 participants
Safety - Adverse Events Follow up Dyspnea	2 participants	2 participants	0 participants
Safety - Adverse Events Follow up Induration	1 participants	1 participants	1 participants
Safety - Adverse Events Follow up Injection site dermatitis	0 participants	0 participants	1 participants
Safety - Adverse Events Follow up Injection site discomfort	2 participants	3 participants	1 participants
Safety - Adverse Events Follow up Tenderness	0 participants	0 participants	1 participants
Safety - Adverse Events Follow up Injection site nodule	2 participants	1 participants	0 participants
Safety - Adverse Events Follow up Injection site warmth	0 participants	1 participants	0 participants
Safety - Adverse Events Follow up pain	4 participants	4 participants	0 participants
Safety - Adverse Events Follow up Swelling	1 participants	0 participants	0 participants
Safety - Adverse Events Follow up Burning sensation	0 participants	0 participants	1 participants
Safety - Adverse Events Follow up Facial nerve disorder	1 participants	0 participants	0 participants
Safety - Adverse Events Follow up Dysphagia	15 participants	21 participants	2 participants
Safety - Adverse Events Follow up Injection site edema	21 participants	27 participants	27 participants
Safety - Adverse Events Follow up Injection site bruising	18 participants	17 participants	20 participants
Safety - Adverse Events Follow up Injection site erythema	7 participants	4 participants	3 participants
Safety - Adverse Events Follow up Injection site hemorrhage	6 participants	10 participants	7 participants
Safety - Adverse Events Follow up Injection site hypoesthesia	15 participants	15 participants	12 participants
Safety - Adverse Events Follow up Injection site mass	5 participants	4 participants	1 participants
Safety - Adverse Events Follow up Injection site pain	34 participants	31 participants	23 participants
Safety - Adverse Events Follow up Injection site paresthesia	0 participants	2 participants	1 participants
Safety - Adverse Events Follow up Injection site pruritus	5 participants	5 participants	6 participants
Safety - Adverse Events Follow up Injection site swelling	17 participants	18 participants	16 participants
Safety - Adverse Events Follow up Localized edema	10 participants	6 participants	3 participants

Adverse Events

RZL-012 50mg/ml

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

RZL-012 34mg/ml

Serious events: 0 serious events

Other events: 51 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Racheli Gueta, Director of Clinical Trials

Raziel Therapeutics

Phone: 97289124670

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	RZL-012 50mg/ml n=50 participants at risk Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses 270 mg for the high doses. Each injection point will be dosed with 7.5 mg for the high dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	RZL-012 34mg/ml n=53 participants at risk Subjects treated with RZL-012 will undergo a single treatment session with 32±4 injections. The maximal number of injections will be 36 with maximal doses of 183.6 mg for the low dose. Each injection point will be dosed with 5.1 mg RZL-012 for the low dose in a volume of 0.15 mL/injection site. RZL-012: small synthetic molecule for submental fat reduction	Placebo n=48 participants at risk Placebo (vehicle) subjects will be injected with a 0.15 mL vehicle per each injection site. The maximal injection volume for all groups will be up to 5.4 mL. Placebo: Placebo
General disorders Injection site edema	42.0% 21/50 • 3 months No difference from clinicaltrials.gov	50.9% 27/53 • 3 months No difference from clinicaltrials.gov	56.2% 27/48 • 3 months No difference from clinicaltrials.gov
Gastrointestinal disorders Dysphagia	30.0% 15/50 • 3 months No difference from clinicaltrials.gov	39.6% 21/53 • 3 months No difference from clinicaltrials.gov	4.2% 2/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site Bruising	36.0% 18/50 • 3 months No difference from clinicaltrials.gov	32.1% 17/53 • 3 months No difference from clinicaltrials.gov	41.7% 20/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site erythema	14.0% 7/50 • 3 months No difference from clinicaltrials.gov	7.5% 4/53 • 3 months No difference from clinicaltrials.gov	6.2% 3/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site hemorrhage	12.0% 6/50 • 3 months No difference from clinicaltrials.gov	18.9% 10/53 • 3 months No difference from clinicaltrials.gov	14.6% 7/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site hypoesthesia	30.0% 15/50 • 3 months No difference from clinicaltrials.gov	28.3% 15/53 • 3 months No difference from clinicaltrials.gov	25.0% 12/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site mass	10.0% 5/50 • 3 months No difference from clinicaltrials.gov	7.5% 4/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site pain	68.0% 34/50 • 3 months No difference from clinicaltrials.gov	58.5% 31/53 • 3 months No difference from clinicaltrials.gov	47.9% 23/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site paraesthesia	0.00% 0/50 • 3 months No difference from clinicaltrials.gov	3.8% 2/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site pruritus	10.0% 5/50 • 3 months No difference from clinicaltrials.gov	9.4% 5/53 • 3 months No difference from clinicaltrials.gov	12.5% 6/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site swelling	34.0% 17/50 • 3 months No difference from clinicaltrials.gov	34.0% 18/53 • 3 months No difference from clinicaltrials.gov	33.3% 16/48 • 3 months No difference from clinicaltrials.gov
General disorders Localized edema	20.0% 10/50 • 3 months No difference from clinicaltrials.gov	11.3% 6/53 • 3 months No difference from clinicaltrials.gov	6.2% 3/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site hypersensitivity	4.0% 2/50 • 3 months No difference from clinicaltrials.gov	1.9% 1/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site induration	14.0% 7/50 • 3 months No difference from clinicaltrials.gov	13.2% 7/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
General disorders injection site movement impairment	6.0% 3/50 • 3 months No difference from clinicaltrials.gov	1.9% 1/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
Nervous system disorders dizziness	4.0% 2/50 • 3 months No difference from clinicaltrials.gov	3.8% 2/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
Nervous system disorders headache	6.0% 3/50 • 3 months No difference from clinicaltrials.gov	7.5% 4/53 • 3 months No difference from clinicaltrials.gov	6.2% 3/48 • 3 months No difference from clinicaltrials.gov
Nervous system disorders facial paralysis	6.0% 3/50 • 3 months No difference from clinicaltrials.gov	1.9% 1/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
Nervous system disorders hypoaesthesia	6.0% 3/50 • 3 months No difference from clinicaltrials.gov	0.00% 0/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
Respiratory, thoracic and mediastinal disorders dysphonia	4.0% 2/50 • 3 months No difference from clinicaltrials.gov	3.8% 2/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
Respiratory, thoracic and mediastinal disorders dyspnea	4.0% 2/50 • 3 months No difference from clinicaltrials.gov	3.8% 2/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
General disorders induration	2.0% 1/50 • 3 months No difference from clinicaltrials.gov	1.9% 1/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site dermatitis	0.00% 0/50 • 3 months No difference from clinicaltrials.gov	0.00% 0/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site discomfort	4.0% 2/50 • 3 months No difference from clinicaltrials.gov	5.7% 3/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
General disorders Tenderness	0.00% 0/50 • 3 months No difference from clinicaltrials.gov	0.00% 0/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site nodule	4.0% 2/50 • 3 months No difference from clinicaltrials.gov	1.9% 1/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
General disorders Injection site warmth	0.00% 0/50 • 3 months No difference from clinicaltrials.gov	1.9% 1/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
General disorders pain	8.0% 4/50 • 3 months No difference from clinicaltrials.gov	7.5% 4/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
General disorders Swelling	2.0% 1/50 • 3 months No difference from clinicaltrials.gov	0.00% 0/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov
Nervous system disorders Burning sensation	0.00% 0/50 • 3 months No difference from clinicaltrials.gov	0.00% 0/53 • 3 months No difference from clinicaltrials.gov	2.1% 1/48 • 3 months No difference from clinicaltrials.gov
Nervous system disorders Facial nerve disorder	2.0% 1/50 • 3 months No difference from clinicaltrials.gov	0.00% 0/53 • 3 months No difference from clinicaltrials.gov	0.00% 0/48 • 3 months No difference from clinicaltrials.gov