A superiority study to compare the effect of Panzyga versus placebo in patients with pediatric acute-onset neuropsychiatric syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]

Trial duration

20 Mar 2023 → 31 Oct 2024

Decision date (initial)

2024-05-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Octapharma Pharmazeutika Produktionsges.m.b.H.

External identifiers

EU CT number

2024-511673-30-00

EudraCT number

2020-000867-21

WHO UTN

U1111-1303-9248

ClinicalTrials.gov

NCT04508530

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

The primary objective of this study is to confirm that Panzyga is superior to placebo (0.9% w/v sodium chloride) for reducing the severity of symptoms associated with PANS in pediatric patients.

Secondary objectives 2

1. 1. Verify the sustainability of the reduction of the severity of symptoms in pediatric patients treated with Panzyga
2. 2. Assess the efficacy of Panzyga treatment in reducing functional impairment associated with PANS.

Conditions and MedDRA coding

Pediatric acute-onset neuropsychiatric syndrome (PANS)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Patients ≥6 to ≤17 years of age.
2. 2. Confirmed diagnosis of moderate to severe PANS with prominent and stable obsessive-compulsive disorder (OCD) symptoms (i.e. Clinical Global Impression (CGI)—Severity-OCD rating of ≥ 4 or higher on 2 ratings without a change of more than 1 unit between measurements) based on the following criteria: a. Abrupt dramatic onset of OCD meeting DSM-5 diagnostic criteria for OCD as confirmed by the MINI-KID-7 b. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset, from at least two of the following seven categories, that are not better explained by a known neurologic or medical disorder, such as Sydenham chorea (SC), systemic lupus erythematosus, Tourette disorder, or other: • Anxiety (particularly, separation anxiety) • Emotional lability (extreme mood swings) and/or depression • Irritability, aggression and/or severely oppositional behaviors • Behavioral (developmental) regression (examples, talking baby talk, throwing temper tantrums, etc.)• Deterioration in school performance • Sensory or motor abnormalities • Somatic signs and symptoms, including sleep disturbances, bed wetting or urinary frequency
3. 3. Signed informed consent of patient's legal representative(s)/guardians(s). If patients are old enough to understand the risks and benefits of the study (as determined by each institution), they should provide written assent/consent.
4. 4. Legal representative(s)/guardians(s) must be capable of understanding and complying with the relevant aspects of the study protocol.
5. Patients who will additionally meet the following optional inclusion criteria will be identified as patients with Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS): 1. An episodic (relapsing-remitting) course of symptom severity 2. Temporal association between symptoms onset or exacerbation and infections with group A streptococcal infection (GAS, positive throat culture and/or anti-GAS antibody titers)

Exclusion criteria 23

1. 1. Onset of current PANS episode more than 12 months prior to first investigational medicinal product (IMP) treatment.
2. 2. a. In patients with relapsing episodes: Onset of initial PANS episode more than 24 months prior to first IMP treatment. b. In patients with relapsing episodes: Absence of significant improvement and stabilization between the episodes according to investigator's judgment.
3. 3. Contraindications to receiving intravenous immunoglobulin (IVIG), including: a. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response, to immunoglobulin, blood or plasma derived products, or any component of Panzyga. b. Immunoglobulin (Ig) A deficiency with antibodies to IgA (<7 mg/dL). c. Hyperviscosity syndromes or known or suspected hypercoagulable conditions as inferred from clinical history, which can increase risks of thrombosis associated with IVIG administration. d. History of arterial or venous thrombotic or thromboembolic events (TEEs) within the last year prior to Baseline. History of acquired or inherited thrombophilia any time prior to Baseline. e. Need for live virus vaccine within three months after receiving study drug. f. Renal dysfunction (creatinine >120 µmol/L or 1.36 mg/dL), history of renal dysfunction, or known risk factor for renal dysfunction (chronic renal insufficiency, diabetes mellitus, taking known nephrotoxic medication). For Italy, estimated glomerular filtration rate (eGFR) needs to be calculated with the 2009 Schwartz equation (eGFR = k * height/Serum creatinine (SCr), where k is 0.413) eGFR must not be below 30.
4. 4. Severely restricted food intake likely to require parenteral nutrition, and <5th percentile BMI-for-age (BMI Percentile Calculator for Child and Teen based on Centers for Disease Control and Prevention growth charts for children and teens ages 2 through 19 years)
5. 5. Body mass index ≥ 40 kg/m2
6. 6. Presence of symptoms consistent with autism or schizophrenia, bipolar disorder, or other psychotic disorder (unless psychotic symptoms have onset coincident with PANS).
7. 7. Presence of serious or unstable medical illness, psychiatric (e.g. high suicide risk) or behavioral symptoms that would make participation unsafe or study procedures too difficult to tolerate.
8. 8. Treatment with systemic corticosteroids within eight weeks before randomization.
9. 9. Treatment with NSAIDs within five days before randomization.
10. 10. Treatment with melatonin within one week before randomization.
11. 11. History of rheumatic fever, including SC (neurological manifestation).
12. 12. Past treatment of neuropsychiatric symptoms with immunomodulatory therapy (such as IVIG, rituximab or mycophenolate mofetil) or plasmapheresis.
13. 13. Initiation of cognitive behavioral therapy (CBT) within eight weeks before randomization.
14. 14. Start of treatment or change in dosing with selective serotonin reuptake inhibitors [SSRIs] within eight weeks before randomization.
15. 15. Treatment with alpha-2 agonists or antipsychotics within eight weeks before randomization.
16. 16. Start of treatment or change in dosing with stimulants (Methylphenidate, Amphetamine and similar products) for Attention-Deficit Hyperactivity Disorder (ADHD) within four weeks prior to randomization.
17. 17. Active use of tetrahydrocannabinol (THC) containing agents within four weeks prior to enrollment or during the trial. Use of cannabidiol- (CBD) / cannabimovone- (CBM) containing agents without THC is allowed if started more than eight weeks before enrollment in a stable dose/frequency.
18. 18. Use of antibiotics or antiviral drugs at therapeutic dose within one week before randomization. Use of antibiotics at a prophylactic dose is allowed if started at least four weeks before randomization (Section 4.2).
19. 19. Severe liver disease (alanine aminotransferase [ALT] three times above normal value).
20. 20. Known hepatitis B, hepatitis C or HIV infection as per patient medical history.
21. 21. Cardiac insufficiency (New York Heart Association [NYHA] classification III-IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment.
22. 22. Medical conditions with symptoms and effects that could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
23. 23. Pregnant and/or lactating women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement of neuropsychiatric symptomatology and behavior in PANS patients determined by clinician-rated CY-BOCS score. The mean changes in the total CY-BOCS score from Baseline to Week 9 will be compared between Panzyga and placebo treatment to demonstrate superiority.

Secondary endpoints 5

1. 1. To assess the durability of the clinical benefit associated with Panzyga treatment, the CY-BOCS score at the end of the follow-up period at Week 18 will be compared to the Week 9 scores within the (Panzyga – Placebo) treatment sequence group to assess the durability of the clinical benefit associated with Panzyga treatment
2. 2. Clinical Global Impression (CGI)
3. 3. Parent & Child OC Impact Scale – Revised (COIS-RP and COIS-RC)
4. 4. The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV, 26 item)
5. 5. Parent Tic Questionnaire (PTQ)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Sponsor organisation

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Address

Oberlaaer Strasse 235, Favoriten Favoriten

City

Vienna

Postcode

1100

Country

Austria

Scientific contact point

Organisation

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Contact name

Clinical Project Manager

Public contact point

Organisation

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Contact name

Clinical Project Manager

Third parties 6

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

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

Application history

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