A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (Glucagon-like Peptide-2 [GLP-2] Analog-Fc Fusion) in Healthy Adult Participants

NCT03859323 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SHP681-101
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the safety and tolerability of single and multiple ascending subcutaneous (SC) doses of SHP681 in healthy adult participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)

  Adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

  From start of study drug administration up to follow-up (Day 29 for SAD)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)

  AE was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

  From start of study drug administration up to follow-up (Day 57 for MAD)

• Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29

  Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in SAD at Day 29 were reported.

  Day 29

• Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36

  Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 36 were reported.

  Day 36

• Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57

  Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 57 were reported.

  Day 57

Secondary Outcomes (23)

• Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)

  Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

• Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)

  Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

• Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)

  Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

• Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)

  Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

• Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)

  Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Study Arms (12)

Single Ascending Dose (SAD): 0.2 mg/kg

EXPERIMENTAL

Participants will receive single subcutaneous (SC) injection of 0.2 mg/kg SHP681 in the abdomen.

Drug: SHP681

Single Ascending Dose (SAD): 0.5 mg/kg

EXPERIMENTAL

Participants will receive single SC injection of 0.5 mg/kg SHP681 in the abdomen.

Drug: SHP681

Single Ascending Dose (SAD): 1 mg/kg

EXPERIMENTAL

Participants will receive single SC injection of 1 mg/kg SHP681 in the abdomen.

Drug: SHP681

Single Ascending Dose (SAD): 2 mg/kg

EXPERIMENTAL

Participants will receive single SC injection of 2 mg/kg SHP681 in the abdomen.

Drug: SHP681

Single Ascending Dose (SAD): 4 mg/kg

EXPERIMENTAL

Participants will receive single SC injection of 4 mg/kg SHP681 in the abdomen.

Drug: SHP681

Single Ascending Dose (SAD): Placebo

PLACEBO COMPARATOR

Participants will receive single SC injection of placebo matched to SHP681 in the abdomen.

Other: Placebo

Multiple Ascending Dose (MAD): 0.2 mg/kg

EXPERIMENTAL

Participants will receive SC injection of 0.2 mg/kg SHP681 once weekly for 5 weeks in the abdomen.

Drug: SHP681

Multiple Ascending Dose (MAD): 0.5 mg/kg

EXPERIMENTAL

Participants will receive SC injection of 0.5 mg/kg SHP681 once weekly for 5 weeks in the abdomen.

Drug: SHP681

Multiple Ascending Dose (MAD): 1 mg/kg

EXPERIMENTAL

Participants will receive SC injection of 1 mg/kg SHP681 once weekly for 5 weeks in the abdomen.

Drug: SHP681

Multiple Ascending Dose (MAD): 2 mg/kg

EXPERIMENTAL

Participants will receive SC injection of 2 mg/kg SHP681 once weekly for 5 weeks in the abdomen.

Drug: SHP681

Multiple Ascending Dose (MAD): 4 mg/kg

EXPERIMENTAL

Participants will receive SC injection of 4 mg/kg SHP681 once weekly for 5 weeks in the abdomen.

Drug: SHP681

Multiple Ascending Dose (MAD): Placebo

PLACEBO COMPARATOR

Participants will receive SC injection of placebo matched to SHP681 once weekly for 5 weeks in the abdomen.

Other: Placebo

Interventions

SHP681 DRUG

Participants will receive SC injection of SHP681 in the abdomen.

Multiple Ascending Dose (MAD): 0.2 mg/kg; Multiple Ascending Dose (MAD): 0.5 mg/kg; Multiple Ascending Dose (MAD): 1 mg/kg; Multiple Ascending Dose (MAD): 2 mg/kg; Multiple Ascending Dose (MAD): 4 mg/kg; Single Ascending Dose (SAD): 0.2 mg/kg; Single Ascending Dose (SAD): 0.5 mg/kg; Single Ascending Dose (SAD): 1 mg/kg; Single Ascending Dose (SAD): 2 mg/kg; Single Ascending Dose (SAD): 4 mg/kg

Placebo OTHER

Participants will receive SC injection of placebo matched to SHP681 in the abdomen.

Multiple Ascending Dose (MAD): Placebo; Single Ascending Dose (SAD): Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
• An understanding, ability, and willingness to fully comply with study procedures and restrictions.
• Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
• Considered "healthy" by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease or condition based on a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.

You may not qualify if:

• History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
• Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or render the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
• Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
• Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
• Known history of alcohol or other substance abuse within the last year.
• Donation of blood or blood products (example \[eg\], plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
• Within 30 days prior to the first dose of investigational product:
• Have used an investigational product (if elimination half-life is less than (\<) 6 days, otherwise 5 half-lives).
• Have been enrolled in a clinical study.
• Have had any substantial changes in eating habits, as assessed by the investigator.
• Use of dipeptidyl peptidase (DPP)-4 inhibitors within 30 days or 5 half-lives, whichever is greater, prior to administration of the investigational product.
• Confirmed systolic blood pressure greater than (\>) 139 millimeters of mercury (mmHg) or \<89mmHg, and diastolic blood pressure \> 89mmHg or \<49 mmHg.
• Twelve-lead ECG demonstrating corrected QT interval by Fredericia (QTcF) \>450 millisecond (msec) at screening. If QTcF exceeds 450 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participant's eligibility.
• Positive screen for alcohol or illicit drugs at screening or Day -1.
• Male participants who consume more than 21 units of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 1, 2019
• Study Start: March 26, 2019
• Primary Completion: January 6, 2020
• Study Completion: January 6, 2020
• Last Updated: February 25, 2021
• Results First Posted: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (1)