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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06700538




Registration number
NCT06700538
Ethics application status
Date submitted
20/11/2024
Date registered
22/11/2024
Date last updated
15/01/2025

Titles & IDs
Public title
Study of ARO-INHBE in Adults With Obesity With and Without Diabetes Mellitus
Scientific title
A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-INHBE in Adult Volunteers With Obesity With and Without Diabetes Mellitus
Secondary ID [1] 0 0
AROINHBE-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 0 0
Condition category
Condition code
Diet and Nutrition 0 0 0 0
Obesity
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARO-INHBE
Treatment: Drugs - Placebo
Treatment: Drugs - Tirzepatide

Experimental: Part 1: ARO-INHBE - ARO-INHBE in single (Day 1) or multiple (Days 1 and 29) ascending doses

Placebo comparator: Part 1: Placebo - Placebo in single (Day 1) or multiple (Days 1 and 29) matching doses

Experimental: Part 2: ARO-INHBE + Tirzepatide - ARO-INHBE at selected dose on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 mg) up to Day 169

Placebo comparator: Part 2: Placebo + Tirzepatide - Placebo dose on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 mg) up to Day 169


Treatment: Drugs: ARO-INHBE
SC injection

Treatment: Drugs: Placebo
calculated volume to match active treatment by SC injection

Treatment: Drugs: Tirzepatide
SC injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Part 1 single dose: up to Day 113 End of Study (EOS), Part 1 multiple doses: up to Day 169 (EOS), Part 2: up to Day 169 (EOS)
Secondary outcome [1] 0 0
Pharmacokinetics (PK) of ARO-INHBE: Maximum observed Plasma Concentration (Cmax)
Timepoint [1] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29): Through 48 hours post first and second dose
Secondary outcome [2] 0 0
PK of ARO-INHBE: Time to Maximum Observed Plasma Concentration (Tmax)
Timepoint [2] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [3] 0 0
PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
Timepoint [3] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [4] 0 0
PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUC0-t)
Timepoint [4] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [5] 0 0
PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-8)
Timepoint [5] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [6] 0 0
PK of ARO-INHBE: Terminal Half-life (t1/2)
Timepoint [6] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [7] 0 0
PK of ARO-INHBE: Apparent Systemic Clearance (CL/F)
Timepoint [7] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [8] 0 0
PK of ARO-INHBE: Apparent Terminal-phase Volume of Distribution (Vz/F)
Timepoint [8] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [9] 0 0
PK of ARO-INHBE: Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after dosing (amount excreted: Ae)
Timepoint [9] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [10] 0 0
PK of ARO-INHBE: Fraction or Percentage of Administered Drug Excreted in Urine from Time 0 to 24 Hours after Dosing (Fe)
Timepoint [10] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Secondary outcome [11] 0 0
PK of ARO-INHBE: Renal Clearance (CLr)
Timepoint [11] 0 0
Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)

Eligibility
Key inclusion criteria
* Obesity, defined as Body Mass Index (BMI) between 30 to 50 kg/m2 at Screening
* At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
* Willing, able and motivated to comply with all study assessments and adhere to the protocol schedule, including adherence to a stable diet and exercise routine for the duration of the study
* No abnormal finding of clinical relevance at Screening that, in the opinion of investigator, could adversely impact subject safety or adversely impact study results
* Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the endo of the study or last dose of study medication, whichever is later. Participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study medication, whichever is later.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Self-reported (or documented) weight gain or lose >5% within 3 months prior to Screening
* Use of GLP1R agonists (liraglutide, semaglutide, etc.) for any indication within 6 months prior to Screening
* Use of non-GLP1R medications for weight loss within 3 months prior to Screening, including but not limited to naltrexone/bupropion, orlistat, phentermine/topiramate, and other prescription or over-the-counter medication or supplements taken for weight loss
* Obesity attributable, in the investigator's opinion, to medication use, endocrinologic or monogenic disorders
* History or prior surgical or device-based therapy for obesity
* Use of medications strongly associated with weight gain within 3 months prior to Screening
* Type 1 diabetes mellitus
* History of hyperthyroidism or thyroid-stimulating hormone (TSH) levels <0.4 or >6.0 mIU/L at Screening
* Evidence of clinically significant end-organ disease

Note: Other Inclusion/Exclusion criteria may apply per protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/12/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2026
Actual
Sample size
Target
78
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1/2a double-blind dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of ARO-INHBE in adult participants with obesity (Part 1), and the safety, tolerability and PD of repeat doses of ARO-INHBE in adult participants with obesity with and without type 2 diabetes mellitus receiving tirzepatide (Part 2). Part 2 will commence after evaluation of safety data from Part 1 multiple-dose cohorts through Day 43. The dose for Part 2 will be based upon evaluation of data from Part 1.
Trial website
https://clinicaltrials.gov/study/NCT06700538
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Monitor
Address 0 0
Country 0 0
Phone 0 0
626-304-3400
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06700538