A trial of Lu AF82422 in Participants with Multiple System Atrophy (MSA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

H. Lundbeck A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Apr 2025 → ongoing

Decision date (initial)

2025-03-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

H. Lundbeck A/S (Lundbeck)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

To evaluate the efficacy of amlenetug on clinical progression in participants with MSA.

Secondary objectives 6

1. To evaluate the efficacy of amlenetug on: -global clinical impression, severity of illness - global disability - functionality - disease milestones - health-related quality of life - overall survival
2. To evaluate the clinical meaningfulness of amlenetug
3. To evaluate the efficacy of amlenetug on disease progression, measured by brain MRI
4. To determine population pharmacokinetic parameter of amlenetug
5. To evaluate the safety and tolerability of amlenetug in participants with MSA during the placebo-controlled period and OLE period.
6. To evaluate the immunogenecity of amlenetug

Conditions and MedDRA coding

Multiple System Atrophy

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Lundbeck is committed to share the data from this clinical trial when the product is approved in Europe and/or the United States. Please visit www.lundbeck.com for more information about our clinical data sharing policy and processes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. The participant is capable of communicating with site staff.
2. The participant is able to read and understand the ICF.
3. The participant has signed the trial specific ICF.
4. The participant's caregiver is able to read and understand the Caregiver's Informed Consent Form.
5. The participant's caregiver has signed the Caregiver's Informed Consent Form.
6. The participant is ≥ 40 and lesser than/equal 75 years of age at the screening Visit.
7. The participant has a reliable caregiver who will be available throughout the trial to complete caregiver observer questionnaires when carer/ observer-reported outcomes are performed. A caregiver is defined as a person who spends approximately 3 hours or more with the participant per week and can inform on the participant's level of functioning.
8. The participant and participant's caregiver are willing and able to attend trial appointments within the specified time windows.
9. The participant has a diagnosis of clinically established MSA-P or MSA-C, or clinically probable MSA-P or MSA-C, according to the 2022 MDS criteria for diagnosis of MSA at the screening visit.
10. The participant had onset of motor MSA symptoms (i.e., parkinsonian and/or cerebellar) within 5 years prior to the Screening Visit in the judgement of the investigator.
11. The participant has an anticipated survival of >3 years, in the opinion of the investigator, at the Screening Visit.
12. The participant has an UMSARS Part I score lesser than/equal16 (omitting item 11 on sexual function) at the Screening Visit.
13. The participant has a cognitive performance score ≥22, evaluated by the MoCA at the Screening Visit. Add one point for an individual who has 12 years or less of formal education.
14. The participant has suitable peripheral venous access for IMP administration and blood sampling.
15. The man must: - have been surgically sterlised (bilateral surgical vasectomy or bilateral orchiectomy) prior to Screening Visit OR - remain sexually abstinent, when this is in line with his preferred and usual lifestyle OR - engage exclusively in same-sex relationships OR - engage in sexual relationships with a partner who is a woman of non-childbearing potential, defined as: - a woman who had her last natural menstruation ≥12 months prior to the screening Visit OR - a woman who was surgically sterlised (bilateral fallopian tubal ligation, bilateral salpingo-oophorectomy, or bilateral oophorectomy) or had hysterectomy prior to the screening visit - Bilateral fallopian tubal ligation is not considered a criterion for non clildbearing potential in GB OR - agree to avoid impregnating his partner, if the partner is considered to be of childbearing potential, from the Screening Visit until at least 5 months after the last dose of IMP by using contraception as specified below AND -not donate sperm from the Screening Visit until atleast 5 months after the last dose of IMP Contraception Methods to be used by Men and their partners who are woman of Childbearing Potential: - By the man: condom (to avoid the risk of drug exposure through the ejaculate [which also applies to a vasectomised male] to the sexual partner, including a pregnant partner) - By the woman of childbearing potential: contraception is recommended
16. The woman, if considered to be of childbearing potential* must: - remain sexually abstinent when this is in line with her preferred and usual lifestyle OR - engage exclusively in same-sex relationships OR - have a male partner who was surgically sterilised (bilateral surgical vasectomy or bilateral orchiectomy) prior to the Screening Visit OR - agree to avoid becoming pregnant from the Screening Visit until at least 5 months after the last dose of IMP by using a highly effective method of contraception as specified below AND - not donate ova from the Screening Visit until at least 5 months after the last dose of IMP Contraception Method: - Highly effective contraception is defined as one that results in a low failure rate (that is, - <1% per year) when used consistently and correctly, for example, combined (oestrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intra-vaginal, or transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system. * The woman is considered to be of non-childbearing potential if she: - has not had her menses for ≥12 months without an alternative medical cause; if this needs to be confirmed, an FSH test can be used, unless the participant is taking hormonal replacement therapy or using hormonal contraception. OR - was surgically sterilised (bilateral fallopian tubal ligation, bilateral salpingo-oophorectomy, or bilateral oophorectomy) or had a hysterectomy prior to the Screening Visit - Bilateral fallopian tubal ligation is not considered a criterion for non-childbearing potential in GB.

Exclusion criteria 19

1. The participant is a member of the site staff or of their immediate families or is a subordinate (or immediate family member of a subordinate) to any of the site staff
2. The participant has previously been enrolled in this trial
3. The participant has previously been dosed with Lu AF82422
4. The participant has taken any active IMP within 3 months or 5 half-lives of that product, whichever is longer, prior to the first dose of IMP
5. The participant is pregnant, breastfeeding, intends to become pregnant, or is of childbearing potential and not willing to use adequate contraceptive methods.
6. The participant has a history of severe drug allergy, anaphylaxis or hypersensitivity or known or suspected hypersensitivity or intolerance to the IMP, or its excipients
7. The participant has 2 or more first degree relatives with a history of MSA
8. The participant, if of MSA-P subtype, has unexplained anosmia (not explained by other common causes such as allergic rhinitis or smoking, nasal structural lesions, or nasal surgery) on olfactory testing at the Screening Visit
9. The participant has contraindications for MRI scanning
10. The participant has evidence (clinically or on MRI) and/or history of any clinically significant disease or condition other than MSA, that is, in the investigator’s opinion, likely to affect CNS functioning, e.g., serious neurological disorder, other intracranial or systemic disease. Abnormalities (space-occupying lesions, vascular lesions, tumours, stroke, etc.) on MRI are to be discussed with the Lundbeck Medical Expert or the CRO Medical Monitor before the participant is enrolled
11. The participant has a current diagnosis of movement disorders that could mimic MSA, e.g., Parkinson’ disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, pharmacological, or post-encephalitic parkinsonism, per investigator discretion. Participants who have previously been incorrectly diagnosed with Parkinson’s disease will not be excluded
12. The participant has a history of neurosurgical procedures including deep brain stimulation that could, in the investigator’s opinion, interfere with the assessments of safety or efficacy.
13. The participant has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin or adequately treated cervical intraepithelial neoplasia, that has not been in remission for >5 years prior to the first dose of IMP
14. The participant has any other disorder for which the treatment takes priority over treatment of MSA or is likely to interfere with the trial treatment or impair treatment compliance.
15. The participant takes or has taken concomitant medication that is disallowed or allowed with restrictions (see Protocol), or it is anticipated that the participant will require treatment with at least one of these medications during the trial
16. The participant has an abnormal ECG that is considered clinically significant by the investigator at the Screening Visit, and that could, in the opinion of the investigator, interfere with the assessments of safety, or interfere with the conduct of the trial
17. The participant has one or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the Screening Visit, or has a disease or takes medication that could, in the opinion of the investigator, interfere with the assessments of safety, or tolerability, or interfere with the conduct or interpretation of the trial.
18. The participant is at significant risk of suicide based on medical history, mental status, investigator judgement, or the C-SSRS (answer of ‘yes’ to suicidal ideation question 4 or 5 or any suicidal behaviour during the last 6 months prior to the Screening Visit)
19. The participant is, in the opinion of the investigator, unlikely to comply with the Clinical Trial Protocol or is unsuitable for any reason

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Please refer Protocol for information related to primary end points as considered company confidential information by the sponsor
2. Please refer Protocol for information related to primary end points as considered company confidential information by the sponsor

Secondary endpoints 29

1. Non-EU regional-specific : slowing in clinical progression, as assessed by changes from baseline up to Week 72 in UMSARS TS
2. Non-EU regional-specific : Change from baseline to Week 72 in UMSARS TS
3. EU regional-specific: Change from baseline to Week 72 in UMSARS TS
4. Global Endpoints: slowing in clinical progression, as assessed by changes from baseline up to Week 72 in UMSARS Part I score
5. Global Endpoints: slowing in clinical progression, as assessed by changes from baseline up to Week 72 in UMSARS Part II score
6. Global Endpoints: change from baseline to Week 72 in mUMSARS, UMSARS Part I and UMSARS Part II
7. Global Clinical Impression: Please refer to the protocol for relevant information as the sponsor considers this to be confidential company information
8. Global Clinical Impression: change from baseline to Week 72 in PGI-S score
9. Global Clinical Impression: change from baseline to Week 72 in OGI-S score
10. Global Disability: Please refer to the protocol for relevant information as the promoter considers this to be confidential company information
11. Functionality: change from baseline to Week 72 in SE-ADL score
12. Disease Milestones: change from baseline to Week 72 in UMSARS Part I item 1: Speech -  time-to-disability, as defined by the time it takes (from baseline) to reach a total of 2 points across 1 or more selected UMSARS Part I items (2. Swallowing; 4. Cutting; 5. Dressing; 6. Hygiene; 7. Walking) or death
13. Health-related Quality of Life: change from baseline to Week 72 in EQ-5D-5L domain and VAS scores
14. Health-related Quality of Life: change from baseline to Week 72 in MSA-QoL domain scores
15. Overall survival: combined clinical progression and survival: joint-rank score based on change from baseline in mUMSARS at Week 72 or time-to-death, whichever comes first
16. Overall survival: Please refer to the protocol for relevant information as the promoter considers this to be confidential company information
17. Clinical meaningfulness: response, defined as an absolute increase in mUMSARS score of <5, <7, and <9 points at Week 72
18. Clinical meaningfulness: response, defined as an absolute increase in UMSARS TS of <16, <21, and <26 points at Week 72
19. MRI biomarkers: percentage change from baseline to Week 72 in brain volume in brain ROIs; primary ROIs: pons and cerebellum; secondary ROIs: caudate nucleus, putamen, brain stem and total grey matter, as measured using vMRI
20. Pharmacokinetics: exposure to Lu AF82422 (expressed as plasma concentrations, AUC, and Cmax)
21. Safety placebo-controlled period: TEAEs (treatment-emergent adverse events)
22. Safety placebo-controlled period: actual values and changes from baseline and Week 72 to Week 144 in clinical safety laboratory test values, and vital signs
23. Safety placebo-controlled period: PCS clinical safety laboratory test values, vital signs, and weight changes
24. Safety placebo-controlled period: suicidal ideation and behaviour based on the C-SSRS
25. Safety OLE period: TEAEs (treatment-emergent adverse events)
26. Safety OLE period: actual values and changes from baseline and Week 72 to Week 144 in clinical safety laboratory test values, and vital signs
27. Safety OLE period: PCS clinical safety laboratory test values, and vital signs
28. Safety OLE period: suicidal ideation and behaviour based on the C-SSRS
29. Immunogenicity: development of anti-amlenetug antibodies (ADAs) and titration of ADA-positive samples during the placebo-controlled period and OLE

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

H. Lundbeck A/S

Sponsor organisation

H. Lundbeck A/S

Address

Ottiliavej 9

City

Valby

Postcode

2500

Country

Denmark

Scientific contact point

Organisation

H. Lundbeck A/S

Contact name

H. Lundbeck A/S

Public contact point

Organisation

H. Lundbeck A/S

Contact name

H. Lundbeck A/S

Third parties 10

Locations

5 EU/EEA countries · 34 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 156 files

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

Application history

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