Study of LLG783 in Patients With Peripheral Artery Disease (PAD) and Intermittent Claudication

NCT03194776 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLLG783X22012017-000706-37
• Study Type: interventional
• Target: 46
• Locations: 3 countries
• Sites: 8

Brief Summary

This study is designed to determine whether LLG783 displays the clinical safety and efficacy profile, after multiple i.v. doses, to support further development in patients with PAD and intermittent claudication.

Conditions

Peripheral Artery Disease (PAD); Intermittent Claudication

Keywords

PAD; peripheral artery/arterial disease; peripheral vascular disease; leg pain; claudication; leg pain with exercise; exercise test; walk test

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs), Drug-related AEs, Serious Adverse Events (SAEs) and Deaths

  An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign, including abnormal laboratory findings, symptom or disease) in a participant after providing written informed consent for participation in the study until the end of study visit. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. An SAE is defined as any AE which is is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect in offspring, requires inpatient hospitalization or prolongation of existing hospitalization and is is medically significant.

  Up to 32 Weeks

• Change From Baseline in Maximum Walking Distance (MWD) as Assessed by 6-minute Walk Test (6MWT) at Week 16

  MWD was assessed by the 6MWT prior to dosing was used to evaluate functional capacity of peripheral artery disease (PAD) participants. 6MWT test included measurement of total distance walked in 6 minutes.

  Baseline, Week 16 (Day 113)

Secondary Outcomes (7)

• Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf)

  1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

• Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)

  1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

• Area Under the Serum Concentration-time Curve From Time Zero to Defined Time Point 't' (AUC[0-t])

  1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

• Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)

  1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

• Observed Maximum Serum Concentration (Cmax) Following Drug Administration

  1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

Study Arms (2)

LLG783

EXPERIMENTAL

Patients will receive LLG783 i.v. infusion every 4 weeks for 12 weeks.

Drug: LLG783

Placebo

PLACEBO COMPARATOR

Patients will receive placebo to LLG783 i.v. infusion every 4 weeks for 12 weeks.

Drug: Placebo

Interventions

LLG783 DRUG

LLG783 concentrate solution for infusion/injection suitable for i.v. administration as well as s.c. administration.

LLG783

Placebo DRUG

Placebo to LLG783 concentrate solution for infusion/injection suitable for i.v. administration as well as s.c. administration.

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• claudication, as defined by pain with exertion in either leg;
• On stable medical therapy, including statins, aspirin, and antihypertensive medications (as medically indicated) unless individually contraindicated, for at least 4 weeks prior to the screening visit;
• Vital signs must be within the following ranges:
• body temperature between 35.0-37.5°C
• systolic blood pressure, 90-159 mm Hg
• diastolic blood pressure, 50-99 mm Hg
• pulse rate, 50 - 90 bpm
• Moderately impaired ambulatory function judged by the investigator to be due primarily to PAD and assessed by a maximum walk distance between 50 and 400 meters (inclusive of these values) at the screening 6-minute walk test (6MWT).

You may not qualify if:

• Pregnant or nursing (lactating) women;
• Patients who meet any of the following PAD related criteria:
• Patients actively attending and participating in a supervised exercise rehabilitation program (patients who have already completed such a program and remain symptomatic may be included).
• Patients with any condition other than PAD that limits walking ability.
• Known inflammatory disease of the arteries (other than atherosclerosis; e.g. Thromboangiitis obliterans).
• Clinical evidence of critical limb ischemia including new or non-healing ulcers (felt secondary to critical limb ischemia), new or recent onset of resting pain in the lower extremities particularly at night (felt secondary to critical limb ischemia) and/or gangrene of the lower extremities (Fontaine stage III-IV) .
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150 days after stopping of investigational drug.
• Any of the following concomitant cardiovascular or metabolic conditions or diseases:
• Myocardial infarction within 6 months of screening.
• Stroke within 6 months of screening.
• History of clinically significant ventricular arrhythmias, according to the discretion of the investigator, within 6 months of screening.
• Significant ECG abnormalities, according to the discretion of the investigator, at screening.
• History of sustained and clinically significant supraventricular arrhythmias (e. g. associated with hemodynamic compromise) within 6 months of screening.
• Chronic heart failure New York Heart Association Class III or IV.
• Known presence of aortic aneurysm \> 5 cm.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Jacksonville, Florida, 32216, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43215, United States

Location

Novartis Investigative Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Berlin, 10787, Germany

Location

Novartis Investigative Site

Magdeburg, 39112, Germany

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Taipei, 11217, Taiwan

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication; Peripheral Vascular Diseases

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, patient and investigator-blinded, placebo controlled, parallel group study

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 21, 2017
• Study Start: September 20, 2017
• Primary Completion: September 7, 2018
• Study Completion: December 27, 2018
• Last Updated: January 5, 2021
• Results First Posted: January 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

US (2); TW (2); DE (4)