Evaluate Safety, Tolerability, Pharmacokinetics and Immunogenicity of MEDI7352 in Healthy Volunteers

NCT04770428 | Completed Phase 1

• 2 other identifiers: D5680C000042020-005982-14
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate safety, tolerability, pharmacokinetics and immunogenicity of MEDI7352 in healthy participants.

Conditions

Painful Osteoarthritis of the Knee

Keywords

MEDI7352; Bi-specific fusion protein; Multiple doses; Subcutaneous route; Pharmacokinetics; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events (AEs)

  To evaluate the safety and tolerability of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route

  Upto Final Follow-up (Day 84) or Early Termination

Secondary Outcomes (11)

• Maximum concentration (Cmax) for MEDI7352

  1st dose: pre-dose (Day 1), post-dose Day 2, 4, 6, 8, 10 and 12; 2nd and 3rd doses: pre-dose (Days 15 and 29) and 7 days post-dose (Days 22 and 36); 4th dose: pre-dose (Day 43), post-dose Days 44, 46, 48, 50, 52, 54, 57, 64, 71

• Time of Cmax (tmax) for MEDI7352

  1st dose: pre-dose (Day 1), post-dose Day 2, 4, 6, 8, 10 and 12; 2nd and 3rd doses: pre-dose (Days 15 and 29) and 7 days post-dose (Days 22 and 36); 4th dose: pre-dose (Day 43), post-dose Days 44, 46, 48, 50, 52, 54, 57, 64, 71

• Area under the serum concentration-time curve from time 0 to infinity (AUCinf) for MEDI7352

  1st dose: pre-dose (Day 1), post-dose Day 2, 4, 6, 8, 10 and 12; 2nd and 3rd doses: pre-dose (Days 15 and 29) and 7 days post-dose (Days 22 and 36); 4th dose: pre-dose (Day 43), post-dose Days 44, 46, 48, 50, 52, 54, 57, 64, 71

• Area under the serum concentration-time curve from time 0 to the time of the last quantifiable serum concentration (AUClast) for MEDI7352

  1st dose: pre-dose (Day 1), post-dose Day 2, 4, 6, 8, 10 and 12; 2nd and 3rd doses: pre-dose (Days 15 and 29) and 7 days post-dose (Days 22 and 36); 4th dose: pre-dose (Day 43), post-dose Days 44, 46, 48, 50, 52, 54, 57, 64, 71

• Area under the serum concentration-time curve for the dosing interval (AUCτ) for MEDI7352

  1st dose: pre-dose (Day 1), post-dose Day 2, 4, 6, 8, 10 and 12; 2nd and 3rd doses: pre-dose (Days 15 and 29) and 7 days post-dose (Days 22 and 36); 4th dose: pre-dose (Day 43), post-dose Days 44, 46, 48, 50, 52, 54, 57, 64, 71

Study Arms (4)

Cohort 1: Japanese MEDI7352

EXPERIMENTAL

Randomized Japanese participants will receive single doses of MEDI7352 subcutaneously.

Drug: MEDI7352

Cohort 1: Japanese Placebo

PLACEBO COMPARATOR

Randomized Japanese participants will receive matching placebo subcutaneously.

Drug: Placebo

Cohort 2: Caucasian MEDI7352

EXPERIMENTAL

Randomized Caucasian participants will receive single doses of MEDI7352 subcutaneously.

Drug: MEDI7352

Cohort 2: Caucasian Placebo

PLACEBO COMPARATOR

Randomized Caucasian participants will receive matching placebo subcutaneously.

Drug: Placebo

Interventions

MEDI7352 DRUG

A dose of MEDI7352 will be administered as two 1.5 mL injections in the abdomen. Following an overnight fast of at least 8 hours, each participant will receive a single dose of MEDI7352 on 4 occasions.

Cohort 1: Japanese MEDI7352; Cohort 2: Caucasian MEDI7352

Placebo DRUG

Matching placebo will be administered as two 1.5 mL injections in the abdomen. To maintain the double-blind requirements, the placebo volume administered will be equivalent to the MEDI7352 volume administered for each dosing. Following an overnight fast of at least 8 hours, each participant will receive matching placebo on 4 occasions.

Cohort 1: Japanese Placebo; Cohort 2: Caucasian Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy male or female of non childbearing potential participants aged 18 to 65 (inclusive) years for Caucasian participants and 20 to 65 (inclusive) years for Japanese participants with suitable veins for cannulation or repeated venepuncture
• Japanese or Caucasian ethnicity
• Post-menopausal women must have had ≥ 12 months of spontaneous amenorrhea with an follicle stimulating hormone (FSH) concentration consistently ≥ 40 mIU/mL and a negative serum or urine pregnancy test result at Screening or Day -1. Surgically sterile women must have had a hysterectomy, and bilateral ovariectomy (oophorectomy), must provide documentation of the procedure and have had a negative serum or urine pregnancy test at Screening or Day -1. An intermediate or positive pregnancy test, can be confirmed by repeating the pregnancy test and demonstrating non-doubling of β-human chorionic gonadotropin levels every 48 to 72 hours
• Men who are biologically capable of fathering children must agree and commit to use of an adequate form of a highly effective method of contraception and refrain from sperm donation for the duration of the Treatment Period and for 3 months after the last administration of study treatment
• Body mass index 18 and 30 kg/m\^2, weight at least 50 kg
• No clinically significant abnormality identified on medical or laboratory evaluation at Screening unless the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures
• lead electrocardiogram recorded at Screening and Day -1 that is normal for the age group and shows no significant abnormalities that will compromise safety
• Physical examinations with no significant findings at Screening and on Day -1.

You may not qualify if:

• Participation in another clinical study or use of any experimental medication, device, or biologic with an investigational product (IP) within 5 half-lives of that IP or 3 months (whichever is longer) prior to first dosing
• Participation in another study investigating any form of anti-NGF or anti-TNF therapy in the 6 months prior to Screening and until after the final Follow-up Visit
• Any positive laboratory result at screening for COVID-19
• Blood donation or draw in excess of 400 mL within 2 months prior to Screening or plasma donation in excess of 50 mL within 30 prior to Screening
• Inability to comply with study-related restrictions and requirements related to consumption of alcohol, provision of meals and snacks, nicotine use, activity, blood donation, and contraception
• History of severe allergy/hypersensitivity reactions or ongoing severe allergy/hypersensitivity reactions, or history of hypersensitivity to immunizations or immunoglobulins or other biological modalities
• History of any significant psychiatric disorder
• Any clinically significant illness, such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, GI, urologic, immunologic, rheumatologic or endocrine disease or disorder
• Recent (within the last 3 months) or active infection considered to be clinically significant, or any infection for which there are unresolved medical sequelae
• Clinically significant osteoarthritis (OA) currently affecting a major joint in the upper or lower extremity or axial spine; or other degenerative disease affecting any joint in participants for whom, there is an identified risk of osteonecrosis, rapidly progressing OA, subchondral insufficiency fractures, neurogenic arthropathy, or analgesia-induced arthropathy; or history of trauma or surgery involving any major joint or axial spine
• Radiological significant abnormalities reported on baseline MRI of hips and knees that are considered to present a risk of osteonecrosis, rapidly progressive OA, subchondral insufficiency fractures; or other coincidental finding(s) that present a risk to the safety or welfare of the participant
• History of excessive alcohol intake
• History of cancer within 5 years, with the exception of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix or non-progressive prostate cancer
• History of drug abuse or positive test for drugs of abuse or alcohol
• Use of prescription or non-prescription drugs, including vitamins and herbal and dietary supplements, within 7 days or 5 half-lives of the drug (whichever is longer) prior to the administration of study treatment

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is double-blinded with regard to treatment (MEDI7352 or placebo) for all placebo-controlled dose groups (groups where placebo and active substance is given in a cohort, ie, the Sponsor, the Investigator, all clinical staff involved in the clinical study, the participants, and the study monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 25, 2021
• Study Start: April 20, 2021
• Primary Completion: December 2, 2021
• Study Completion: December 2, 2021
• Last Updated: December 15, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• 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 rerefer 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 sponsored 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.

Locations

GB (1)