Single Ascending Dose Study of MEDI1341 in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT03272165
• Recruitment Status: Completed
• First Posted: September 5, 2017
• Last Update Posted: March 17, 2022
• Sponsor: AstraZeneca
• Collaborators: Covance; MMS Holdings, Inc; Catalent; Takeda
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

This is a study of single ascending intravenous doses of MEDI1341 or placebo in up to 48 healthy volunteers, aged 18 to 65 years.

The study will include up to 6 planned cohorts; each cohort will comprise 8 subjects.

Each subject will receive a single 60 minute intravenous infusion of MEDI1341 or placebo and will undergo scheduled assessments over a period of 13 weeks.

The main aim of the study is to assess the safety and tolerability of single doses of MEDI1341 in Healthy Volunteers.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: MEDI1341; Drug: Placebo	Phase 1

Detailed Description:

This is a randomized, double-blind, placebo-controlled study of single ascending intravenous doses of MEDI1341 in male and nonfertile female healthy volunteers, aged 18 to 65 years.

The study will include up to 6 planned cohorts; each cohort will comprise 8 subjects. Within each cohort, 6 subjects will be randomized to receive MEDI1341 and 2 will be randomized to receive placebo. A Safety Review Committee will review data from each cohort before progression to the next higher dose cohort occurs.

On Day 1, each randomized subject will receive a single 60 minute intravenous infusion of MEDI1341 or placebo and will undergo scheduled safety, pharmacokinetic, pharmacodynamic, and immunogenicity assessments. Additional study assessments will occur on Days 2, 4, 8, 15, 22, 29, 43, 57, and 92.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects are randomised to one of two groups within a cohort of 8 subjects (N=6 MEDI1341; N=2 placebo)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of MEDI1341 in Healthy Male and Female Volunteers.
• Actual Study Start Date: October 17, 2017
• Actual Primary Completion Date: March 31, 2021
• Actual Study Completion Date: March 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: MEDI1341	Drug: MEDI1341; Intravenous infusion over 60 minutes; Other Name: TAK-341
Placebo Comparator: Placebo	Drug: Placebo; Intravenous infusion over 60 minutes

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: 13 weeks ]
   - Incidence, nature, severity and seriousness
2. Vital Signs [ Time Frame: 13 weeks ]
   - Blood pressure and pulse rate
3. Oral Body Temperature [ Time Frame: 13 weeks ]
   - in Celsius
4. Body weight [ Time Frame: 13 weeks ]
   - in kilograms
5. Height [ Time Frame: 13 weeks ]
   - in meters
6. Body Mass Index (BMI) [ Time Frame: 13 weeks ]
   - Weight and height will be combined to report BMI in kg/m2
7. Safety Laboratory tests [ Time Frame: 13 weeks ]
   - Clinical chemistry, hematology, coagulation, urinalysis
8. Electrocardiograms [ Time Frame: 13 weeks ]
   - rhythm, heart rate, conduction, P-R interval, QRS complex, R-R interval, Q-T interval, and QTcF (Q-T interval corrected by Fridericia's formula)
9. Ophthalmic assessments [ Time Frame: 13 weeks ]
   • a standardized ophthalmic patient-reported outcome questionnaire
   • visual acuity
   • intraocular pressure
   • corneal thickness
   • slit-lamp examination
   • fundoscopy
   • optical coherence tomography
   • visual field assessment

Secondary Outcome Measures :

1. Maximum concentration of Medi1341 [ Time Frame: 13 weeks ]
   - Cmax
2. Time to maximum concentration of Medi1341 [ Time Frame: 13 weeks ]
   - tmax
3. Area under the concentration - time curve of Medi1341 [ Time Frame: 13 weeks ]
   - AUC from zero to the last measurable concentration
4. AUC of Medi1341 from zero to infinity [ Time Frame: 13 weeks ]
   - AUC0-∞
5. Terminal half-life of Medi1341 [ Time Frame: 13 weeks ]
   - t1/2λz
6. Clearance of Medi1341 [ Time Frame: 13 weeks ]
   - CL
7. Volume of distribution of Medi1341 at steady state [ Time Frame: 13 weeks ]
   - Vss
8. Mean residence time of Medi1341 [ Time Frame: 13 weeks ]
   - MRT
9. Total alpha-synuclein concentrations [ Time Frame: 13 weeks ]
   - in plasma
10. Free alpha-synuclein concentrations [ Time Frame: 29 days ]
    - in Cerebrospinal Fluid
11. Anti-Drug Antibodies to MEDI1341 [ Time Frame: 13 weeks ]
    - in serum

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subjects must be healthy, with no clinically significant abnormality identified on the medical or laboratory evaluation at screening
• Subjects must weigh ≥50 kg and must have a body mass index between 18 and 32 kg/m2, inclusive
• Subjects must have a 12-lead ECG recorded at screening that is normal for the appropriate age group and shows no abnormalities that will compromise safety in this study
• Subjects must have no clinically significant findings on the clinical neurological examinations at screening and at baseline or on the ophthalmic examination at screening.

Exclusion Criteria:

• Nicotine use within 6 months before screening
• Considered to be at a high risk of developing a stroke
• Significant medical history of dizziness, blackouts, fainting, or vaso-vagal attacks
• History of any significant ophthalmic disorder, including congenital, genetic or acquired conditions affecting the retina or choroid
• History of severe allergy or history of hypersensitivity to immunizations or immunoglobulins
• History of any significant psychiatric disorder
• History of alcohol abuse
• History of cancer within 5 years of screening
• History of drug abuse
• Any contraindication to Lumbar Puncture
• Any clinically significant abnormality in ECG rhythm, conduction or morphology
• Positive serologic findings at screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies
• Use of prescription or non-prescription drugs
• For female subjects, a positive serum or urine pregnancy test result at screening

Contacts and Locations

Locations

United States, Texas

Research Site

Dallas, Texas, United States, 75247

United States, Wisconsin

Research Site

Madison, Wisconsin, United States, 53704

Sponsors and Collaborators

AstraZeneca

Covance

MMS Holdings, Inc

Catalent

Takeda

Investigators

• Principal Investigator: Jeanelle Kam, MD, CPI; Covance Dallas CRU, USA
• Principal Investigator: John E Blanchard, MD; Covance Madison CRU, USA

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03272165
• Other Study ID Numbers: D6340C00001
• First Posted: September 5, 2017
• Last Update Posted: March 17, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymised individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsor tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:

Healthy Volunteers; Safety; Tolerability; Pharmacokinetics; Pharmacodynamics; Immunogenicity

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases