Safety, Tolerability & Pharmacokinetics of LEVI-04 in Healthy Volunteers and Patients With Osteoarthritis Knee Pain

NCT03227796 | Completed Phase 1 DMC

• 1 other identifier: LEVI-04_17_01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

This is a first-in-human, phase 1, single centre, placebo-controlled, double-blind, single ascending dose study of LEVI-04 in heathy volunteers and osteoarthritis patients (with pain attributed to osteoarthritis of the knee)

Conditions

Healthy Volunteers; Osteoarthritis

Keywords

osteoarthritis; knee; healthy; volunteer; LEVI-04

Outcome Measures

Primary Outcomes (4)

• Incidence of treatment emergent adverse events [Safety and tolerability]

  adverse events; laboratory tests; electrocardiograms and injection site reaction assessments

  Change from Baseline at Day 56 post-dose for healthy volunteers and change from Baseline at Day 105 post-dose for osteoarthritis patients

• Change from Baseline in neurological assessments [Safety and tolerability] - SAS

  Neurological assessment (Survey of Autonomic Symptoms (SAS) Questionnaire)

  Change from Baseline at Day 56 post-dose for healthy volunteers and change from Baseline at Day 105 post-dose for osteoarthritis patients

• Change from Baseline in neurological assessments [Safety and tolerability] - BCTQ

  Neurological assessment (Boston Carpal Tunnel Questionnaire (BCTQ)

  Change from Baseline at Day 56 post-dose for healthy volunteers and change from Baseline at Day 105 post-dose for osteoarthritis patients

• Change from Baseline in neurological assessments [Safety and tolerability] - 4th finger test

  Neurological assessment (the carpal tunnel syndrome (CTS) 4th finger neurological test or Total Neuropathy Score nurse)

  Change from Baseline at Day 56 post-dose for healthy volunteers and change from Baseline at Day 105 post-dose for osteoarthritis patients

Secondary Outcomes (8)

• Pharmacokinetics of single ascending intravenous doses of LEVI-04 in healthy volunteers and osteoarthritis patients - maximum concentration

  Up to Day 56 post-dose for healthy volunteers and up to Day 105 post-dose for osteoarthritis patients

• Pharmacokinetics of single ascending intravenous doses of LEVI-04 in healthy volunteers and osteoarthritis patients - time to maximum concentration

  Up to Day 56 post-dose for healthy volunteers and up to Day 105 post-dose for osteoarthritis patients

• Pharmacokinetics of single ascending intravenous doses of LEVI-04 in healthy volunteers and osteoarthritis patients - Area Under the Curve

  Up to Day 56 post-dose for healthy volunteers and up to Day 105 post-dose for osteoarthritis patients

• Pharmacokinetics of single ascending intravenous doses of LEVI-04 in healthy volunteers and osteoarthritis patients - half-life

  Up to Day 56 post-dose for healthy volunteers and up to Day 105 post-dose for osteoarthritis patients

• Pharmacokinetics of single ascending intravenous doses of LEVI-04 in healthy volunteers and osteoarthritis patients - clearance

  Up to Day 56 post-dose for healthy volunteers and up to Day 105 post-dose for osteoarthritis patients

Other Outcomes (5)

• Pharmacodynamics of LEVI-04 in osteoarthritis patients - pain relief (rescue medication)

  Up to Day 105 for osteoarthritis patients

• Pharmacodynamics of LEVI-04 in osteoarthritis patients - pain relief (NRS-11)

  Up to Day 105 for osteoarthritis patients

• Pharmacodynamics of LEVI-04 in osteoarthritis patients - pain relief (WOMAC)

  Up to Day 105 for osteoarthritis patients

Study Arms (16)

Cohort 1 Healthy Volunteers Active

EXPERIMENTAL

LEVI-04 0.003 mg/kg single intravenous dose Healthy Volunteers

Drug: LEVI-04

Cohort 2 Healthy Volunteers Active

EXPERIMENTAL

LEVI-04 Dose Level 2 (planned 0.01 mg/kg) single intravenous dose Healthy Volunteers

Drug: LEVI-04

Cohort 3 Healthy Volunteers Active

EXPERIMENTAL

LEVI-04 Dose Level 3 (planned 0.03 mg/kg) single intravenous dose Healthy Volunteers

Drug: LEVI-04

Cohort 4 Osteoarthritis Patients Active

EXPERIMENTAL

LEVI-04 Dose Level 3 (planned 0.03 mg/kg) single intravenous dose Osteoarthritis Patients

Drug: LEVI-04

Cohort 5 Osteoarthritis Patients Active

EXPERIMENTAL

LEVI-04 Dose Level 4 (planned 0.1 mg/kg) single intravenous dose Osteoarthritis Patients

Drug: LEVI-04

Cohort 6 Osteoarthritis Patients Active

EXPERIMENTAL

LEVI-04 Dose Level 5 (planned 0.3 mg/kg) single intravenous dose Osteoarthritis Patients

Drug: LEVI-04

Cohort 7 Osteoarthritis Patients Active

EXPERIMENTAL

LEVI-04 Dose Level 6 (planned 1.0 mg/kg) single intravenous dose Osteoarthritis Patients

Drug: LEVI-04

Cohort 8 Healthy Volunteers Active

EXPERIMENTAL

LEVI-04 Dose Level 7 (planned 3.0 mg/kg) single intravenous dose Healthy Volunteers

Drug: LEVI-04

Cohort 1 Healthy Volunteers Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Healthy Volunteers

Drug: Placebo

Cohort 2 Healthy Volunteers Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Healthy Volunteers

Drug: Placebo

Cohort 3 Healthy Volunteers Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Healthy Volunteers

Drug: Placebo

Cohort 4 Osteoarthritis Patients Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Osteoarthritis Patients

Drug: Placebo

Cohort 5 Osteoarthritis Patients Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Osteoarthritis Patients

Drug: Placebo

Cohort 6 Osteoarthritis Patients Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Osteoarthritis Patients

Drug: Placebo

Cohort 7 Osteoarthritis Patients Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Osteoarthritis Patients

Drug: Placebo

Cohort 8 Healthy Volunteers Placebo

PLACEBO COMPARATOR

Placebo to match LEVI-04 single intravenous dose Healthy Volunteers

Drug: Placebo

Interventions

LEVI-04 DRUG

LEVI-04 intravenous infusion

Cohort 1 Healthy Volunteers Active; Cohort 2 Healthy Volunteers Active; Cohort 3 Healthy Volunteers Active; Cohort 4 Osteoarthritis Patients Active; Cohort 5 Osteoarthritis Patients Active; Cohort 6 Osteoarthritis Patients Active; Cohort 7 Osteoarthritis Patients Active; Cohort 8 Healthy Volunteers Active

Placebo DRUG

Placebo intravenous infusion

Cohort 1 Healthy Volunteers Placebo; Cohort 2 Healthy Volunteers Placebo; Cohort 3 Healthy Volunteers Placebo; Cohort 4 Osteoarthritis Patients Placebo; Cohort 5 Osteoarthritis Patients Placebo; Cohort 6 Osteoarthritis Patients Placebo; Cohort 7 Osteoarthritis Patients Placebo; Cohort 8 Healthy Volunteers Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index 18.0-\<32.0 kg/m2 (healthy volunteers) and 18.0-\<40.0 kg/m2 (osteoarthritis patients)
• Willing and able to give written fully informed consent
• Men with female partners of childbearing potential must agree to follow the requirements for effective contraception throughout the study and for 112 days post-dose
• Women of non childbearing potential
• Healthy volunteers (aged 18 to 65 years) willing to give written consent to have data entered into the Over-volunteering Prevention System
• Osteoarthritis patients (aged 30-80 years) with diagnosis of mild to moderate osteoarthritis of the knee, with X-ray confirmation as diagnosed by a trained radiology reviewer
• Osteoarthritis patients willing to discontinue all pain medication, except rescue medication (paracetamol), from the run-in visit until the end of the study
• Osteoarthritis patients with a Numerical Rating Scale-11 pain score of between 5 and \<9, inclusive, in the index knee at screening. If taking regular pain medication, should show an increase of at least 1 point following washout of analgesia. The average pain score of between 5 and \<9, inclusive, based on four of the seven daily readings during the seven day initial pain assessment period

You may not qualify if:

• Women of childbearing potential, or who are pregnant or lactating
• Clinically relevant abnormal history, physical findings, electrocardiograph, or laboratory values at screening that could interfere with the objectives of the trial or the safety of the subject
• Presence of acute or chronic illness or history of chronic illness (other than osteoarthritis, controlled diabetes, asthma or hypertension for osteoarthritis patients), sufficient to invalidate participation in the trial or make it unnecessarily hazardous
• Impaired endocrine, thyroid, hepatic, respiratory (other than asthma that has been controlled by the use of acceptable medication for at least 3 months prior to screening) or renal function; or history of any psychotic mental illness or clinically significant psychiatric disorder
• History of carpal tunnel syndrome with signs or symptoms within one year before screening or a Boston Carpal Tunnel Questionnaire score \>3
• Moderate or severe carpal tunnel syndrome based on the 4th finger neurological test or Total Neuropathy Score nurse
• History of cancer within 5 years before screening, except for appropriately treated cutaneous basal cell or squamous cell cancers; cervical cancer; and low grade stable prostate cancer
• History, diagnosis, or signs of neurological disease including but not limited to: stroke; peripheral or autonomic neuropathy; diabetic neuropathy; multiple sclerosis; epilepsy or seizure disorder with history of seizure within last 2 years; myopathy; Alzheimer's disease or other types of dementia; head trauma within last 2 years; and episodic lower limb radiculopathy, nerve compression, or sciatica (provided diagnosed as due to nerve root compression and not as a manifestation of systemic neuropathy or radiculopathy)
• Survey of Autonomic Symptoms score of at least 3
• Uncontrolled type 1 diabetes or type 2 diabetes with HbA1c \<7.5% (type 1 diabetics and type 2 diabetics that have been controlled by acceptable medication for at least three months prior to screening are permitted if HbA1c \< 7.5%).
• History or signs and symptoms of coronary heart disease or stroke
• QTcF interval \<330 msec or ≥430 msec for males, and ≥450 msec for females at the screening examination, unless judged not clinically significant by an investigator
• Presence of Chronic Obstructive Pulmonary Disease
• Moderate / severe depression indicated by a score of ≥10 out of 24 in the Personal Health Questionnaire Depression Scale
• History or presence of severe adverse reaction to any drug or a history of sensitivity to mannitol or histidine

Sponsors & Collaborators

• Levicept: lead
• Hammersmith Medicines Research: collaborator
• MAC Clinical Research: collaborator

Study Sites (2)

MAC Clinical Research - Early Phase Unit

Manchester, Greater Manchester, M13 9NQ, United Kingdom

Location

Hammersmith Medicines Research

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Denisa Wilkes, MUDr

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: First-in-human, phase 1, placebo-controlled, double-blind, single ascending dose study in heathy volunteers and osteoarthritis patients

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: July 24, 2017
• Study Start: July 28, 2017
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)