A Phase 2 Study to Investigate Efficacy and Safety of HZN-1116 in Participants With Sjögren’s Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics Ireland Designated Activity Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Nov 2024 → 28 Apr 2026

Decision date (initial)

2024-10-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Horizon Therapeutics

External identifiers

EU CT number

2023-507680-19-00

ClinicalTrials.gov

NCT06312020

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety, Dose response, Efficacy, Therapy, Pharmacogenetic

"Population #1:
- To evaluate the effect of HZN-1116 on systemic manifestations of Sjӧgren’s Syndrome (SS) in participants with moderate-to-severe systemic disease activity
Population #2:
- To evaluate the effect of HZN-1116 on patient-reported symptoms of SS in participants with unsatisfactory symptom state"

Secondary objectives 3

1. Population #1: - To evaluate the effect of HZN-1116 on measures of systemic activity and patientreported outcomes (PRO) in participants with SS.
2. Population #2: - To evaluate the effect of HZN-1116 on patient-reported symptoms of SS and PROs in participants with SS
3. Population #1 and #2: -To characterize the PK of HZN-1116 in participants with SS -To assess the immunogenicity of multiple doses of HZN-1116 in participants with SS

Conditions and MedDRA coding

Sjögren’s Syndrome

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adults, ≥ 18 and ≤ 75 years of age at time of informed consent (the minimum age for adult participants can be > 18 years of age based on country-specific regulations). Participants must be capable of providing their own informed consent.
2. Diagnosed with SS by meeting the 2016 ACR/EULAR Classification Criteria. If SS diagnosis based on positive anti-Ro autoantibody, anti-Ro positivity must be confirmed by central lab.
3. Population #1 only: a. Have an ESSDAI score of ≥ 5 at screening despite symptomatic (eg, nonsteroidal anti-inflammatory drugs [NSAIDs]) or local therapy at screening. The following domains will be scored but they will not contribute to the minimum ESSDAI score of 5 required for inclusion as these domains may have lower sensitivity to change over duration of trial: peripheral nervous system, central nervous system, and pulmonary. Population #2 only: a. Have an ESSPRI score of ≥ 5 at screening. b. Have an ESSDAI score of < 5 at screening.
4. Positive for either anti-Ro autoantibodies or rheumatoid factor (RF), or both at screening (as per the definition of the standard central laboratory test).
5. Residual salivary gland function as defined by whole stimulated salivary flow > 0.1 mL/min or with residual lacrimal gland function defined as an unanesthetized Schirmer’s test ≥ 1mm/5 min.
6. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from signing the informed consent form (ICF) and must agree to continue using such precautions through the end of the study (or 15 weeks after the last dose of IP administration, if participant withdraws from study) and refrain from ova donation during this period; cessation of contraception after this point should be discussed with a responsible physician.
7. Nonsterilized male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide (unless spermicide is not available or restricted per local regulations) till the end of the study and refrain from sperm donation during this period and for a minimum of 15 days after the last dose of IP administration.
8. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the United States [US], European Union [EU] Data Privacy Directive General Data Protection Regulation [GDPR] in the EU) obtained from the participant prior to performing any protocolrelated procedures, including screening evaluations.
9. Fully vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)according to current local authority guidelines, if any, at least 2 weeks prior to screening unless individual refuses vaccination. Initial or subsequent coronavirus disease 2019 (COVID-19) vaccine administration is permitted during the study as long as it is not administered during the screening period or within 2 weeks after Dose 1; if vaccine is to be administered during this window, screening should be delayed to complete vaccination

Exclusion criteria 11

1. Concomitant systemic sclerosis.
2. Active malignancy or history of malignancy within the last 5 years, except as follows: a. In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to screening; OR b. Cutaneous basal cell carcinoma following presumed curative therapy.
3. Individuals who are pregnant or lactating or planning to become pregnant during the study.
4. Individuals with known history of severe allergy or reaction to any component of the IP formulation or to any other biologic therapy.
5. Individuals with any severe or life-threatening cardiovascular (including vasculitis and uncontrolled hypertension), respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, or systemic disorder or any other condition that in the opinion of the Investigator, would place the individual at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of participant safety or study results.
6. Individuals who, in the opinion of the Investigator, are unable or unwilling to comply with protocol requirements (eg, active drug or alcohol abuse or for other reasons), including the completion of the Diary for Assessing Sjögren’s Patient Reported Index (DASPRI).
7. Individuals who have a positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. A positive test for hepatitis B at screening is defined as: (1) positive for HBsAg OR (2) positive for either HBcAb or HBsAb and HBV DNA detected above the LLOQ by reflex testing by the central laboratory at screening. Individuals with a positive test for or a history of treatment for hepatitis C are excluded except if they have a documented sustained viral response to antiviral drugs approved for the treatment of hepatitis C, defined as an undetectable viral level of hepatitis C RNA at least 24 weeks following completion of therapy. Individuals with advanced fibrosis or cirrhosis due to hepatitis C cannot be enrolled
8. Individuals with a positive test for SARS-CoV-2 on the day of randomization. Only those with symptoms suggestive of SARS-CoV-2 at randomization or significant exposure to COVID-19 within 10 days prior to randomization, should be tested. Individuals with COVID-19 or COVID-19 exposure can delay randomization up to 2 weeks with sponsor approval and randomize once recovered; otherwise, they will need to rescreen.
9. Individuals with: a. A history of more than one episode of herpes zoster and/or opportunistic infections (see Section 10.3 [Appendix 3]) in the last 12 months, with the exception of noninvasive herpes simplex at any site, oral candidiasis, vaginal candidiasis, or cutaneous fungal infections, which are permitted within the prior 12 months unless of unusual severity. Individuals with a prior history of ophthalmic herpes zoster will be excluded. b. Active infections requiring systemic treatment at the time of screening or through randomization, or history of more than 2 infections requiring IV antibiotics within 12 months prior to screening
10. Individuals who have received live (attenuated) vaccine within the 4 weeks prior to randomization. Non-live vaccines are permitted during the study (see Inclusion Criterion 9for COVID-19 vaccines).
11. Last administration of experimental biologic or oral agents < 6 months or 5 half-lives, whichever is longer, before screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Population #1:Change from baseline in European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index (ESSDAI) total score at Week XX
2. Population #2:Change from baseline in European Alliance of Associations for Rheumatology Sjögren’s Syndrome Patient Reported Index (ESSPRI) total score at Week XX

Secondary endpoints 12

1. Population #1: - Change from baseline in ESSDAI total score at Week XX
2. Population #1: - Proportion of participants achieving ESSDAI[5] response at Week XX and XX without premature discontinuation from treatment and without receiving rescue or potentially confounding therapy
3. Population #1: - Change from baseline in tender joint count (TJC) and swollen joint count (SJC) at the Week XX and XX time points
4. Population #1: - Change from baseline in 36-item Short Form Survey (SF-36) physical component score (PCS) and mental component score (MCS) at the Week XX and XX time points
5. Population #1: - Change from baseline in PROMIS-Fatigue SF-10a at Week XX and Week XX
6. Population #2: - - Change from baseline in DASPRI total score at Week XX
7. Population #2: - Proportion of participants achieving ESSPRI[1.5] response without premature discontinuation from treatment and without receiving rescue or potentially confounding therapy at Week XX
8. Population #2: - Change from baseline in ESSPRI -pain, -fatigue, and -dryness domains at Week XX
9. Population #2: - Change from baseline in SF-36 PCS and MCS at Week XX
10. Population #2: - Change from baseline in PROMIS-Fatigue SF-10a at Week XX
11. Population #1 and #2: - PK of HZN-1116
12. Population #1 and #2: - Proportion of participants who develop anti-drug antibodies (ADA) over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics Ireland Designated Activity Company

Sponsor organisation

Horizon Therapeutics Ireland Designated Activity Company

Address

Pottery Road, Dun Laoghaire Dun Laoghaire

City

Dublin

Postcode

A96 F2A8

Country

Ireland

Scientific contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Amgen Europe B.V Contact point for union

Public contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Amgen Europe B.V Contact point for union

Third parties 19

Locations

11 EU/EEA countries · 51 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 160 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications