Phase III Study To Compare The Effect of Panzyga Versus Placebo in Patients With Pediatric Acute-onset Neuropsychiatric Syndrome (PANS/PANDAS)

A Superiority Phase III Study To Compare The Effect of Panzyga Versus Placebo in Patients With Pediatric Acute-onset Neuropsychiatric Syndrome (PANS/PANDAS)

A Superiority Study To Compare The Effect of Panzyga Versus Placebo in Patients with Pediatric Acute-onset Neuropsychiatric Syndrome

Study Overview

• Status: Completed
• Conditions: Pediatric Acute-Onset Neuropsychiatric Syndrome
• Intervention / Treatment: Other: Placebo; Biological: Panzyga

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Genova, Italy, 16147
    • Octapharma Research Site
  • Roma, Italy, 00161
    • Octapharma Research Site
  • Roma, Italy, 00186
    • Octapharma Research Site
• Sweden
  • Gothenburg, Sweden, 41685
    • Octapharma Research Site
  • Stockholm, Sweden, 17164
    • Octapharma Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Octapharma Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Octapharma Research Site
  • California
    • Los Angeles, California, United States, 90024
      • Octapharma Research Site
    • Palo Alto, California, United States, 94305
      • Octapharma Research Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Octapharma Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Octapharma Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Octapharma Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients ≥6 to ≤17 years of age.

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:

   1. Abrupt dramatic onset of OCD meeting DSM-5 diagnostic criteria for OCD as confirmed by the MINI-KID-7

   2. 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. 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. Legal representative(s)/guardians(s) must be capable of understanding and complying with the relevant aspects of the study protocol.

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

1. Onset of current PANS episode more than 12 months prior to first investigational medicinal product (IMP) treatment.

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. Contraindication to receiving intravenous immunoglobulin (IVIG), including:

   1. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response, to immunoglobulin, blood or plasma derived products, or any component of Panzyga.
   2. Immunoglobulin (Ig) A deficiency with antibodies to IgA (<7 mg/dL).
   3. Hyperviscosity syndromes or known or suspected hypercoagulable conditions as inferred from clinical history, which can increase risks of thrombosis associated with IVIG administration.
   4. 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.
   5. Need for live virus vaccine within three months after receiving study drug.
   6. 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) [2]. eGFR must not be below 30.
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. Body mass index ≥ 40 kg/m2
6. Presence of symptoms consistent with autism or schizophrenia, bipolar disorder, or other psychotic disorder (unless psychotic symptoms have onset coincident with PANS).
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. Treatment with systemic corticosteroids within eight weeks before randomization.
9. Treatment with NSAIDs within five days before randomization.
10. Treatment with melatonin within one week before randomization
11. History of rheumatic fever, including SC (neurological manifestation).
12. Past treatment of neuropsychiatric symptoms with immunomodulatory therapy (such as IVIG, rituximab or mycophenolate mofetil) or plasmapheresis.
13. Initiation of cognitive behavioral therapy (CBT) within eight weeks before randomization.
14. Start of treatment or change in dosing with selective serotonin reuptake inhibitors [SSRIs] within eight weeks before randomization.
15. Treatment with alpha-2 agonists or antipsychotics within eight weeks before randomization.
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. 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. 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. Severe liver disease (alanine aminotransferase [ALT] three times above normal value).
20. Known hepatitis B, hepatitis C or HIV infection as per patient medical history.
21. Cardiac insufficiency (New York Heart Association [NYHA] classification III-IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment.
22. Medical conditions with symptoms and effects that could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
23. Pregnant and/or lactating women.
24. Female patients of childbearing potential unwilling to use a protocol-required method of contraception (as per protocol Section 7.3.9 b) from Screening throughout the study treatment period and for four weeks following the last dose of study drug. A woman of childbearing potential is defined as a fertile woman or adolescent, from the beginning of menstruation, unless permanently sterile.
25. Participation in another interventional clinical trial that is either blinded or involves an investigational (not approved) product within three months before Baseline or during the course of the clinical study. Participation in observational clinical trials or open-label trials involving an approved product may be permitted after consultation with the medical monitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: Panzyga; Panzyga 10% IVIG	Biological: Panzyga; Panzyga 10% IVIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in CY-BOCS Score From Baseline to Week 9	The primary endpoint of this study was the percentage change of neuropsychiatric symptomatology and behavior in PANS patients determined by clinician-rated Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score. The CY-BOCS scale score is a clinician-rated, semi-structured interview for rating the presence or absence, as well as the severity of obsessive-compulsive symptoms. The CY-BOCS yields a total obsession score, a total compulsion score and combined total score (minimum total CY-BOCS score=0, maximum total CY-BOCS score=40). The mean percentage change in the total CY-BOCS score from Baseline to Week 9 was calculated and compared between Panzyga and Placebo treatment to demonstrate superiority. A value of 0 means there was no change from baseline to week 9. Negative values indicate a worse outcome. Positive values mean a better outcome.	9 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Total CY-BOCS Score From Week 9 to Week 18 Within the (Panzyga - Placebo) Treatment Sequence Group	The CY-BOCS scores at the end of the follow up period were compared with the Week 9 scores to examine the durability of any clinical benefit following Panzyga treatment in the first 9-week treatment period and whether there was any worsening after crossing over to placebo treatment. The CY-BOCS scale score is a clinician-rated, semi-structured interview for rating the presence or absence, as well as the severity of obsessive-compulsive symptoms. The CY-BOCS yields a total obsession score, a total compulsion score and combined total score (minimum total CY-BOCS score=0, maximum total CY-BOCS score=40). The mean percentage change of the total CY-BOCS score at Week 18 to the Week 9 score was calculated within the (Panzyga - Placebo) treatment sequence group. A value of 0 means there was no change from Week 9 to Week 18. Negative values indicate a worse outcome. Positive values mean a better outcome.	9 Weeks (Week 9 to Week 18)
Clinical Global Impression - Improvement (CGI-I) Score at Week 9	The CGI-I rating scale was used to assess behavioral changes in PANS patients. The Clinical Global Impression - Improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and is rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. The mean CGI-I scores at Week 9 were compared between Panzyga and placebo treatment.	9 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients With PANS Improvement From Baseline to Week 9	The percentage of patients who showed PANS improvement was measured by Clinical Global Impression - Improvement (CGI-I) rating. "The Clinical Global Impression - Improvement is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a Baseline state at the beginning of the intervention and is rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse." PANS improvement was defined as a CGI-I rating of 1 (Very much Improved), 2 (Much improved), or 3 (Minimally Improved). The percentages of improved patients at Week 9 were compared to baseline between Panzyga and placebo treatment.	9 Weeks

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): August 27, 2024
• Study Completion (Actual): October 30, 2024

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: August 7, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Pediatric acute-onset neuropsychiatric syndrome; Panzyga
• Other Study ID Numbers: NGAM-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No