Trial Outcomes & Findings for CLINICAL PROTOCOL to Investigate the Long-term Safety and Efficacy of Metreleptin in Various Forms of Partial Lipodystrophy (NCT NCT02654977)

Last Updated: 2020-11-24

Results Overview

Fasting triglyceride levels after 5 years on metreleptin, measured in mg/dL are compared to fasting triglyceride levels at baseline). The median percent increase (positive numbers) or decrease from baseline is shown, along with the full range.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

5 years on metreleptin or last observation carried forward

Results posted on

2020-11-24

Participant Flow

Participant milestones

Participant milestones
Measure	Metreleptin Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Overall Study STARTED	11
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Metreleptin Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Overall Study Death	1
Overall Study Lost to Follow-up	1
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1
Overall Study Lack of Efficacy	3

Baseline Characteristics

CLINICAL PROTOCOL to Investigate the Long-term Safety and Efficacy of Metreleptin in Various Forms of Partial Lipodystrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metreleptin n=11 Participants Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Age, Categorical <=18 years	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Baseline triglyceride value	204 mg/dL n=5 Participants
Baseline hemoglobin A1c value	8.4 % n=5 Participants

PRIMARY outcome

Timeframe: 5 years on metreleptin or last observation carried forward

Population: Participants with immediate drop out, SAE withdrawal or death were excluded from analysis.

Outcome measures

Outcome measures
Measure	Metreleptin n=8 Participants Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Percent Change in Fasting Triglyceride Levels	55.76 percentage of change from baseline Interval -66.79 to 203.8

SECONDARY outcome

Timeframe: 5 years on metreleptin or last observation carried forward

Population: Percent change in hemoglobin A1c levels (hemoglobin A1c levels are measured in %) Participants with immediate drop out, SAE withdrawal or death were excluded from analysis.

Fasting hemoglobin A1c levels after 5 years on metreleptin, measured in % are compared to fasting Hemoglobin levels at baseline). Thus, for example, a change from 10% to 5% would be a -50% change (or 50% decrease). The median percent increase (positive numbers) or decrease from baseline is shown, along with the full range.

Outcome measures

Outcome measures
Measure	Metreleptin n=8 Participants Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Percent Change in Hemoglobin A1c Levels	2.55 percentage of change from baseline Interval -27.52 to 25.0

Adverse Events

Metreleptin

Serious events: 8 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Metreleptin n=11 participants at risk Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Surgical and medical procedures anterior cervical discectomy	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) labia majora dermatofibrosarcoma protuberans	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Metabolism and nutrition disorders hyperglycemia	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders onset of type 1 diabetes	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Metabolism and nutrition disorders Onset of hypertriglyceridemia	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Hepatobiliary disorders autoimmune hepatitis	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders diabetic ketoacidosis	9.1% 1/11 • Number of events 4 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders hypokalemia	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders abdominal pain	9.1% 1/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders pancreatitis	9.1% 1/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Respiratory, thoracic and mediastinal disorders pleural effusion	18.2% 2/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Immune system disorders metreleptin neutralizing antibodies	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Respiratory, thoracic and mediastinal disorders acute hypoxia	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders left shoulder pain	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Nervous system disorders nonepilogenic seizures	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations clinical sepsis	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders splenic flexure colitis fluid collection	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders multiple rib fractures	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders splenic laceration	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Reproductive system and breast disorders uterine bleeding	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Respiratory, thoracic and mediastinal disorders shortness of breath	9.1% 1/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Nervous system disorders dizziness	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Cardiac disorders chest pain with elevated troponin	9.1% 1/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Cardiac disorders atrial flutter	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Cardiac disorders sudden cardiac death	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Cardiac disorders chronic heart failure exacerbation	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders cholecystitis	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders esophageal spasms	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)

Other adverse events

Other adverse events
Measure	Metreleptin n=11 participants at risk Metreleptin open-label Metreleptin: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Endocrine disorders weight loss	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Metabolism and nutrition disorders elevated liver function tests	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders worsening of chronic back pain	18.2% 2/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Nervous system disorders hyperesthesia	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations sinus infection	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders extremity weakness	18.2% 2/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations cold	27.3% 3/11 • Number of events 3 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders acid reflux	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations cellutitus	18.2% 2/11 • Number of events 5 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Renal and urinary disorders kidney stone	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations strep throat	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Skin and subcutaneous tissue disorders reticular rash	18.2% 2/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations urinary tract infection	27.3% 3/11 • Number of events 5 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders hypoglycemia	18.2% 2/11 • Number of events 4 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders nausea	9.1% 1/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Nervous system disorders headache	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders worsening vitamin D deficiency	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Nervous system disorders worsening imbalance	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders worsening diabetes	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders worsening weakness	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations upper respiratory tract infection	27.3% 3/11 • Number of events 3 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders vomiting	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations bronchitis	18.2% 2/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders increase in appetite	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Cardiac disorders cardiac chest pain	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Respiratory, thoracic and mediastinal disorders lung nodule	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Blood and lymphatic system disorders elevated blood platelets	18.2% 2/11 • Number of events 2 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders knee pain	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Reproductive system and breast disorders vaginal spotting	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders Spinal pain	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations vaginal yeast infection	9.1% 1/11 • Number of events 3 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Metabolism and nutrition disorders elevated low density cholesterol	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders worsening of restless leg syndrome	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders low blood iron level	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations infected tooth	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations kidney infection	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Metabolism and nutrition disorders thyroid nodules	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Psychiatric disorders intermittent suicidal ideation	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders abdominal pain	27.3% 3/11 • Number of events 3 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Blood and lymphatic system disorders increased blood protein levels	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Psychiatric disorders worsening depression	27.3% 3/11 • Number of events 3 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders right wrist pain	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders right wrist numbness	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders lower right leg numbness	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Reproductive system and breast disorders irregular periods	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Gastrointestinal disorders worsening of fecal incontinence	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Eye disorders retinopathy lesion	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders frozen shoulder	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Cardiac disorders abnormal stress test	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations viral illness	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Respiratory, thoracic and mediastinal disorders worsening cough	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Endocrine disorders increased creatitine levels	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Infections and infestations blocked parotid gland	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders leg pain	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Musculoskeletal and connective tissue disorders ostearthritis dissicans	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)
Psychiatric disorders worsening anxiety	9.1% 1/11 • Number of events 1 • 5 years (from baseline visit to year 5 study visit or date of study participant early termination)

Additional Information

Dr. Elif Oral

University of Michigan

Phone: 734-615-7271

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place