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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04744363




Registration number
NCT04744363
Ethics application status
Date submitted
16/12/2020
Date registered
9/02/2021
Date last updated
23/05/2022

Titles & IDs
Public title
Pharmacokinetics, Safety and Tolerability Study of AVT04 to EU Approved and US Licensed Stelara (Ustekinumab)
Scientific title
Phase 1, FIH, Randomized, Double-blind, Single-dose, Parallel-group, 3-arm Study Comparing the PK, Safety, Tolerability, and Immunogenicity Profiles of AVT04, EU-approved Stelara®, and US-licensed Stelara® in Healthy Adult Subjects
Secondary ID [1] 0 0
AVT04-GL-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriasis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Stelara PFS

Experimental: AVT04 45 mg SC - Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen

Active Comparator: US Stelara 45 mg SC - Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen

Active Comparator: EU Stelara 45 mg SC - Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen


Treatment: Drugs: Stelara PFS
Pre filled syringes filled with AVT04 and Stelara
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area under the plasma concentration-time curve AUC0-inf
Timepoint [1] 0 0
From Baseline to day 92
Primary outcome [2] 0 0
Maximum serum concentration
Timepoint [2] 0 0
From Baseline to day 92
Secondary outcome [1] 0 0
Ustekinumab serum concentration-time profile following single-dose administration
Timepoint [1] 0 0
From Baseline to day 92
Secondary outcome [2] 0 0
The secondary PK parameters to be assessed are: AUC0-t
Timepoint [2] 0 0
From Baseline to day 92
Secondary outcome [3] 0 0
Adverse Events
Timepoint [3] 0 0
From screening to day 92
Secondary outcome [4] 0 0
Immunogenicity assessments include ADAs and NAbs
Timepoint [4] 0 0
From screening to day 92
Secondary outcome [5] 0 0
The secondary PK parameters to be assessed are: Tmax
Timepoint [5] 0 0
From screening to day 92
Secondary outcome [6] 0 0
The secondary PK parameters to be assessed are: Kel
Timepoint [6] 0 0
From Screening to day 92
Secondary outcome [7] 0 0
The secondary PK parameters to be assessed are: t1/2
Timepoint [7] 0 0
From Screening to day 92
Secondary outcome [8] 0 0
The secondary PK parameters to be assessed are: Vz/F
Timepoint [8] 0 0
From screening to day 92
Secondary outcome [9] 0 0
The secondary PK parameters to be assessed are: CL/F
Timepoint [9] 0 0
From Screening to day 92

Eligibility
Key inclusion criteria
Subjects are eligible to be included in the study only if all of the following criteria
apply at any time starting from Screening up to Day 1 prior to IP administration:

1. Capable of giving signed informed consent as described in Appendix 1, which includes
compliance with the requirements and restrictions listed in the Informed Consent Form
(ICF) and in this protocol.

2. Male or female subjects.

3. Subjects must be 18 to 55 years old inclusive, at the time of signing the ICF.

4. Have a body weight of 60.0 to 90.0 kg (inclusive) and body mass index (BMI) of 18.5 to
30.0 kg/m2 (inclusive).

5. For Japanese subjects only Is a second-generation Japanese person living abroad and
both parents and grandparents are of Japanese origin, OR Was born in Japan and both
parents and grandparents are of Japanese origin.

6. Medical history without major pathology, according to the PI's judgment.

7. Resting supine systolic blood pressure (BP) of =140 mm Hg and diastolic BP of =90 mm
Hg; other vital signs showing no clinically relevant deviations according to the PI's
judgment.

8. Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically
relevant pathology or showing no clinically relevant deviations as judged by the PI.

9. Glycated hemoglobin (HbA1c) =42 mmol/mol.

10. Clinical safety laboratory results are within the reference ranges or showing no
clinically relevant deviations as judged by the PI.

11. Have a negative urine drug screen (opiates, methadone, cocaine, amphetamines
[including ecstasy and methamphetamines], cannabinoids, barbiturates, and
benzodiazepines) and a negative alcohol breath test.

12. Tested negative for TB, hepatitis B surface antigen (HBsAg), hepatitis B core
antibodies (anti-HBc), anti-hepatitis C virus (HCV) antibodies, and anti-human
immunodeficiency virus (HIV) 1/2 antibodies at Screening.

13. Nonsmoker or occasional smoker, ie, smokes =10 cigarettes (or equivalent of tobacco-
or nicotine containing products) per week within 3 months of Screening, and ability
and willingness to refrain from smoking during confinement at the study site.

14. Ability and willingness to abstain from alcohol from 48 hours prior to drug
administration, during confinement at the study site until discharge, and 24 hours
prior to ambulatory visits.

15. Female subjects are eligible to participate if they are not pregnant (see Appendix 3),
not breastfeeding, and at least ONE of the following conditions applies:

1. Is not a woman of childbearing potential (WOCBP), defined as:

Surgically sterile (documented hysterectomy, bilateral salpingectomy, or
bilateral oophorectomy, as confirmed by review of the subject's medical records,
medical examination, or medical history interview), or Postmenopausal (defined as
no menses for 12 months without an alternative medical cause. A high
follicle-stimulating hormone [FSH] level in the postmenopausal range may be used
to confirm a postmenopausal state in women not using hormonal contraception or
hormonal replacement therapy [HRT]. However, in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient). Female subjects on HRT and
whose menopausal status is in doubt will be required to use 1 of the non estrogen
hormonal highly effective contraception methods (Appendix 3) from Screening
(signing the ICF) until at least 13 weeks after IP administration if they wish to
continue their HRT during the study. Otherwise, they must discontinue HRT to
allow confirmation of postmenopausal status before study enrollment.

2. Is a WOCBP who agrees to use a highly effective method of contraception (Appendix
3) consistently and correctly from Screening (signing the ICF) until at least 13
weeks after IP administration.

16. Nonsterilized male subjects with female partners of childbearing potential are
eligible to participate if they agree to ONE of the following from Screening (signing
the ICF) until at least 13 weeks after IP administration:

1. Are abstinent from penile-vaginal intercourse as their usual and preferred
lifestyle (abstinent on a long-term and persistent basis) and agree to remain
abstinent.

2. Agree to use a male condom and have their partner use of a contraceptive method
with a failure rate of <1% per year as described in Appendix 3 when having
penile-vaginal intercourse with a WOCBP who is not currently pregnant.

3. Male subjects with a pregnant or breastfeeding partner must agree to remain
abstinent from penile vaginal intercourse or use a male condom during each
episode of penile penetration.

17. In addition, male subjects must refrain from donating sperm from Screening (signing
the ICF) until at least 13 weeks after IP administration.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects are excluded from the study if any of the following criteria apply at any time
starting from Screening up to Day 1 prior to IP administration:

1. Have a history of relevant drug and/or food allergies.

2. Have a history of hypersensitivity to Stelara, AVT04, or their constituents.

3. Have a known history of previous exposure to IL-12 and/or IL-23 inhibitors.

4. Have any past or concurrent medical conditions that could potentially increase the
subject's risks or that would interfere with the study evaluation, procedures, or
study completion. Examples of these include medical history with evidence of
clinically relevant pathology (eg, malignancies or demyelinating disorders).

5. Presence of chronic obstructive pulmonary disease. Childhood asthma is allowed.

6. Presence of type 1 or 2 diabetes mellitus.

7. Have a known history of active or latent TB, except for subjects with documented and
complete adequate treatment of TB or initiation (>1 month) of adequate prophylaxis of
latent TB, with an isoniazid-based regimen.

8. Have resided or traveled in regions where tuberculosis and mycosis are endemic within
90 days before Screening, or who intend to visit such a region during the study period
or within 3 months (12 weeks) after dosing.

9. Any current active infections, including localized infections, or any recent history
(within 1 week prior to study drug administration) of active infections (including
severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] based on a positive
COVID-19 polymerase chain reaction [PCR] nasopharyngeal swab test), cough or fever, or
a history of recurrent or chronic infections.

10. Participation in a clinical study with an IP within 60 days or 5 half-lives of that IP
(if known), whichever is longer, prior to IP administration in the current study.

11. Treatment with nontopical medications (including over-the-counter [OTC] medications
and herbal remedies such as St. John's Wort extract) within 7 days or 5 half lives of
the drug (whichever is longer) prior to IP administration, with the exception of
multivitamins, vitamin C, food supplements and a limited amount of acetaminophen (up
to 2 g in 24 hours, but <1 g in 4 hours) or ibuprofen (<1.2 g per day), which may be
used throughout the study.

12. Have received live vaccines during the past 4 weeks before Screening or have the
intention to receive vaccination during the study period or within 13 weeks after
dosing.

13. Donation of more than 500 mL of blood within 8 weeks prior to drug administration.

14. History of alcohol abuse (with an average intake exceeding 10 drinks/week for women
and 15 drinks/week for men: 1 drink = 360 mL of beer, 150 mL of wine, or 45 mL of
spirits) or drug addiction (including soft drugs like cannabis products).

15. Any persons who are:

1. An employee of the study site, Investigator, contract research organization (CRO)
or Sponsor;

2. A first-degree relative of an employee of the study site, the Investigator, CRO,
or the Sponsor.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/03/2022
Sample size
Target
Accrual to date
Final
294
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Nucleus Network - Brisbane
Recruitment hospital [2] 0 0
Nucleus Network Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alvotech Swiss AG
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Iqvia Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Protocol Title:

A Phase 1, first-in-human, randomized, double-blind, single-dose, parallel-group, 3-arm study
comparing the pharmacokinetic, safety, tolerability, and immunogenicity profiles of AVT04, EU
approved Stelara®, and US-licensed Stelara® in healthy adult subjects

Short Title:

A first-in-human randomized, double-blind study to compare AVT04 with EU-approved Stelara and
US-licensed Stelara as a single-dose subcutaneous injection in healthy adult subjects

Rationale:

Alvotech (hereafter, the Sponsor) is developing AVT04 globally as a proposed biosimilar to
the reference product Stelara (ustekinumab) for subcutaneous (SC) use. This is a
first-in-human (FIH) clinical study with AVT04. The study aims to demonstrate pharmacokinetic
(PK) similarity of the proposed biosimilar test product AVT04 and the reference products EU
approved Stelara and US-licensed Stelara, in addition to evaluating the safety and
tolerability of AVT04, when administered as a single 45 mg/0.5 mL SC dose.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04744363
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul Duijzings, MSc
Address 0 0
Program Lead
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries