Phase 1b/2a Study to Evaluate Safety and Efficacy of Setm... | NCT02041195

NCT02041195

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Setmelanotide Once Daily	Active Comparator	Once daily in the morning, equivalent placebo in evening.	Drug: Setmelanotide Drug: Placebo
Setmelanotide Split Dose	Active Comparator	Split dose, one half in the morning and one half in the evening.	Drug: Setmelanotide
Placebo	Placebo Comparator	Placebo in the morning, placebo in the evening.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Setmelanotide	Drug		Setmelanotide Once Daily Setmelanotide Split Dose	RM-493

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Body Weight - Stage A		Baseline
Percent Change From Baseline in Body Weight at Week 12 - Stage A		Baseline, Week 12
Body Weight - Stage B		Baseline
Percent Change From Baseline in Body Weight at Week 12 - Stage B		Baseline, Week 12
Body Weight - Stage C		Baseline
Percent Change From Baseline in Body Weight at Week 12 - Stage C		Baseline, Week 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - Stage A	An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs that occurred after the start of study drug administration were considered TEAEs.	From first dose up to Day 114
Number of Participants With TEAEs - Stage B	An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs that occurred after the start of study drug administration were considered TEAEs.	From first dose up to Day 114
Number of Participants With TEAEs - Stage C

Secondary Outcomes

Measure	Description	Time Frame
Mean Setmelanotide Concentrations During a 24-Hour Steady State Interval on Day 8 - Stage A		Predose (0 hours) and at 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24 hours after dosing on Day 8
Mean Setmelanotide Concentrations During a 24-Hour Steady State Interval on Day 8 - Stage C

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Be between the ages of 18 and 65 years, inclusive.
Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures.
In good general health, without significant medical history, physical examination findings, or clinical laboratory abnormalities.
Body Mass Index: 30 to 40 Kg/m2.
Stable body weight by participant report (+/- 5 Kg) during previous 6 months.
Blood pressure (<140/90 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications to achieve control and that are intended to remain on a stable dose during the protocol.
Willingness (during screening) and demonstrated ability (as witnessed in the clinic prior to randomization) to self-administer study medication subcutaneously via a once or twice daily SC injection using a small insulin syringe.
Willing to maintain a healthy diet and exercise regime throughout study as recommended by counseling at study start.
Female participants must have negative serum pregnancy test and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method (i.e., sponge), or a double-barrier method of birth control (i.e., condom with spermicide) or abstinence must be used/ practiced throughout the study and for 90 days following the study.
Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months (and confirmed with a screening FSH level in the post-menopausal lab range), do not require contraception during the study.
Males with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study and for 90 days following the study. Male participants must not donate sperm for 90 days following their participation in the study.

Exclusion Criteria:

Fasting blood glucose > than 140 mg/dL.
TSH level outside the normal range.
Creatinine > 1.5 times the upper limit of normal.
Liver function tests > 2 times the upper limit of normal.
Active or history of any significant medical condition including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
Patients with a history of the following:
1. Uncontrolled hypertension;
2. Diabetes requiring medical treatment;
3. Major depressive disorder within the last 2 years;
4. Any lifetime history of a suicide attempt;
5. Any suicidal ideation/behavior in the last month;
6. Other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder, severe eating disorders including bulimia).
A PHQ-9 score of ≥15.
Any suicidal ideation of type 4 or 5 on the C-SSRS.
Prior bariatric surgery.
History or close family history (parents or siblings) of melanoma.
Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist.
Currently treated with anorectic agents or drugs in last 2 months from screening with anorexia as a frequent side event.
Taking more than 2 anti-hypertensive medications.
Acute illness or history of illness, which in the opinion of the Investigator, could pose a threat or harm to the patient or obscure interpretation of laboratory test results or interpretation of study data.
History of any malignancy, past or present, including skin cancer, multiple severely dysplastic nevi, or nevoid basal cell carcinoma.
History of HIV infection or Hepatitis B or C.
History of significant drug hypersensitivity or anaphylaxis.
History of hypersensitivity to proteins (e.g., allergy shots).
Any clinically significant abnormalities on screening laboratories as determined by the Investigator.
Abnormal 12-lead electrocardiogram (ECG) at screening, except minor deviations deemed to be of no clinical significance by the Investigator. QTcF must be < 450 ms.
Received any experimental drugs or devices or have participated in a clinical study within 30 days prior to dosing.
Blood donation greater than 500 mL within 60 days prior to screening or intent to donate up to 30 days after Final Study Visit.
Hospitalization for surgery within the 3 months prior to screening except for minor outpatient procedures, or any planned hospitalizations during the study period.
Poor venous access or inability to tolerate venipuncture.
Inability to attend all study visits or comply with protocol requirements including fasting and restrictions on concomitant medication intake.
Participation in weight loss programs during the study period, including nutritional supplements/ replacements other than as recommended by nutritional counseling provided at study start.
Use of prescription medications on a regular basis with the following exceptions:
1. Contraceptives (must be on for ≥3 months);
2. Hormone replacement therapy (must be on stable dose for ≥3 months);
3. Antihypertensives (<2 medications on a stable dose for ≥ 30 days);
4. Statins (dose must be ≤ half the maximum dose; must be on a stable dose ≥3 months);
5. Thyroxin (stable dose for ≥ 30 days);
6. The last use of any other prescription medication must have been greater than 5 half-lives for the specific medication or at least 14 days prior to randomization, whichever is longer.
Women who are pregnant or are breast feeding.
Previously randomized and dosed in this study or previously exposed to setmelanotide.
History of alcohol or drug abuse within 5 years of Screening Visit.
Any other reason, which in the opinion of the Investigator, would confound proper evaluation of the study.

Contacts/Locations Module

Name	Affiliation	Role
David Meeker, MD	Rhythm Pharmaceuticals, Inc.	Study Chair

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	Stage A: Setmelanotide 0.75 mg BID	Participants received setmelanotide 0.75 milligrams (mg) by subcutaneous (SC) injection twice daily (BID) for approximately 4 weeks while housed in the Phase 1 unit. During the first 4 weeks, participants were advanced to setmelanotide 2 mg SC BID. Thereafter, participants received setmelanotide 2 mg once daily (QD) by SC injection for the rest of the 12-week study with drug self-administration as outpatients.
FG001	Stage A: Setmelanotide 1.5 mg QD	Participants received setmelanotide 1.5 mg by SC injection QD for approximately 4 weeks while housed in the Phase 1 unit. During the first 4 weeks, participants were advanced to setmelanotide 2 mg once daily. Thereafter, participants received setmelanotide 2 mg once daily by SC injection for the rest of the 12-week study with drug self-administration as outpatients.
FG002	Stage A: Placebo 0.75 mg BID	Participants received placebo matched to setmelanotide by SC injection BID for approximately 4 weeks while housed in the Phase 1 unit. Thereafter, participants received placebo matched to setmelanotide QD by SC injection for the rest of the 12-week study with drug self-administration as outpatients.
FG003	Stage A: Placebo 1.5 mg QD	Participants received placebo matched to setmelanotide by SC injection QD for approximately 4 weeks while housed in the Phase 1 unit. Thereafter, participants received placebo matched to setmelanotide QD by SC injection for the rest of the 12-week study with drug self-administration as outpatients.
FG004	Stage B: Setmelanotide 1.5 mg QD	Participants initially received setmelanotide 1.5 mg QD and then advanced to 2 mg QD for the remainder of the 12-week treatment period. All participants self-administered the study drug.
FG005	Stage B: Placebo 1.5 mg QD	Participants received placebo matched to setmelanotide QD for the 12-week treatment period. All participants self-administered the study drug.
FG006	Stage C: Setmelanotide 2 mg QD	Participants received setmelanotide 2 mg QD for the 12-week treatment period. All participants self-administered the study drug.
FG007	Stage C: Placebo 2 mg QD	Participants received placebo matched to setmelanotide QD for the 12-week treatment period. All participants self-administered the study drug.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00010 subjects FG0019 subjects FG0023 subjects FG0033 subjects FG00411 subjects FG0056 subjects FG00629 subjects FG00728 subjects
COMPLETED		FG0008 subjects FG0016 subjects FG0023 subjects FG0033 subjects FG004
NOT COMPLETED		FG0002 subjects FG0013 subjects FG0020 subjects FG0030 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0012 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Stage A: Setmelanotide 0.75 mg BID	Participants received setmelanotide 0.75 mg by SC injection BID for approximately 4 weeks while housed in the Phase 1 unit. During the first 4 weeks, participants were advanced to setmelanotide 2 mg SC BID. Thereafter, participants received setmelanotide 2 mg QD by SC injection for the rest of the 12-week study with drug self-administration as outpatients.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

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

Body Weight - Stage A

Full Analysis Set (FAS) included all participants with a baseline and at least one post-dose efficacy observation. Data from 2 placebo groups were combined for the efficacy analysis.

Posted

Mean

Standard Error

Kilograms (kg)

Baseline

ID	Title	Description
OG000	Stage A: Setmelanotide 0.75 mg BID	Participants received setmelanotide 0.75 mg by SC injection BID for approximately 4 weeks while housed in the Phase 1 unit. During the first 4 weeks, participants were advanced to setmelanotide 2 mg SC BID. Thereafter, participants received setmelanotide 2 mg QD by SC injection for the rest of the 12-week study with drug self-administration as outpatients.
OG001	Stage A: Setmelanotide 1.5 mg QD

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stage A: Setmelanotide 0.75 mg BID	Participants received setmelanotide 0.75 mg by SC injection BID for approximately 4 weeks while housed in the Phase 1 unit. During the first 4 weeks, participants were advanced to setmelanotide 2 mg SC BID. Thereafter, participants received setmelanotide 2 mg QD by SC injection for the rest of the 12-week study with drug self-administration as outpatients.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Muscle strain	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Rhythm Clinical Trials	Rhythm Pharmaceuticals, Inc.	857-264-4280		clinicaltrials@rhythmtx.com

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D050177	Overweight
D009765	Obesity

ID	Term
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases
D001835	Body Weight

Intervention Browse Module

ID	Term
C579663	setmelanotide

Masking Info

Participants received setmelanotide 1.5 mg by SC injection QD for approximately 4 weeks while housed in the Phase 1 unit. During the first 4 weeks, participants were advanced to setmelanotide 2 mg once daily. Thereafter, participants received setmelanotide 2 mg once daily by SC injection for the rest of the 12-week study with drug self-administration as outpatients.

EG0000 affected10 at risk
EG0010 affected9 at risk
EG0020 affected3 at risk
EG0030 affected3 at risk
EG0040 affected11 at risk
EG0050 affected6 at risk
EG0060 affected29 at risk
EG0071 affected28 at risk

EG0003 affected10 at risk

EG0016 affected9 at risk

EG0020 affected3 at risk

EG0031 affected3 at risk

EG0046 affected11 at risk

EG0051 affected6 at risk

EG00617 affected29 at risk

EG0073 affected28 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Dallas	Texas		United States