NCT04777331: PADOVA

A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early Parkinson's Disease

Active, enrolled Phase 2 Results posted Last updated 9 March 2026

What this trial tests

Phase 2 trial testing Prasinezumab in Parkinsons Disease in 586 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

5 May 2021

Primary endpoint
11 September 2024

30 December 2026

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	586
Start date	5 May 2021
Primary completion	11 September 2024
Estimated completion	30 December 2026
Sites	110 locations across France, Italy, Austria, United Kingdom, Poland, Canada, Spain, United States

Drugs / interventions tested

• Prasinezumab — full drug profile →
• Placebo

Conditions studied

• Parkinsons Disease — all drugs for Parkinsons Disease →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 50 to 85, any sex, with Parkinsons Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Primary · From study start to end of DBT period to at least 76 weeks

Time to confirmed motor progression event was the first time point of a worsening event defined as either \>= 5 points increase in MDS-UPDRS Part III score (assessed in "OFF" medication state) from baseline sustained over 2 consecutive assessments or a change in medication after first occurrence of \>= 5 points increase in MDS-UPDRS Part III score from baseline \& before follow-up assessment. MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct ratin

Group	Value	95% CI
DBT Period: Placebo	49.7	40.1 – 58.1
DBT Period: Prasinezumab	61.1	52.3 – 71.9

DBT Period: Time-to-worsening of Participant's Motor Function as Reported by the Participant in the Presence of a Confirmed Motor Progression Event Secondary · From study start to end of DBT period to at least 76 weeks

Time to worsening of the motor function was defined as ≥3 points increase in MDS-UPDRS Part II score from baseline in the presence of a confirmed motor progression event. For the confirmed motor progression event the definition is as per primary endpoint definition. MDS-UPDRS Part II assesses motor experiences of daily living \& contained 13 questions answered by participant. For each question a numeric score is assigned between 0-4, 0 = Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Score range: 0 to 52 with higher score=severe impairment.

Group	Value	95% CI
DBT Period: Placebo	88.3	62.7 – 105.1
DBT Period: Prasinezumab	112.1	81.1 – NA

DBT Period: Time to Meaningful Worsening in Participant Global Impression of Change (PGI-C) Overall Disease Subscale Secondary · From study start to end of DBT period to at least 76 weeks

The PGI is a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (PGI-C) was intended to measure health state changes as reported by the participant on a 7-point scale (1=Very much improved to 7=Very much worse). The meaningfulness of the change was assessed and reported by the participant.

Group	Value	95% CI
DBT Period: Placebo	36.1	29.9 – 42.1
DBT Period: Prasinezumab	44.4	38.1 – 52.1

DBT Period: Time to Meaningful Worsening in Clinician Global Impression of Change (CGI-C) Overall Disease Subscale Secondary · From study start to end of DBT period to at least 76 weeks

The CGI was a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (CGI-C) was intended to measure health state changes as reported by the clinician on a 7-point scale (1=Very much improved to 7=Very much worse).

Group	Value	95% CI
DBT Period: Placebo	52.1	44.1 – 59.9
DBT Period: Prasinezumab	60.6	56.1 – 67.3

DBT Period: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV Secondary · From study start to end of DBT period to at least 76 weeks

MDS-UPDRS Part IV assessed motor complications of symptomatic treatment, dyskinesias, and motor fluctuations. The rater completed this assessment only for participants on L-Dopa treatment.

Group	Value	95% CI
DBT Period: Placebo	91.1	77.0 – 107.6
DBT Period: Prasinezumab	100.1	81.0 – 117.1

DBT Period: Change in Motor Function From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score Secondary · From baseline up to Week 76

MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment.

Group	Value	95% CI
DBT Period: Placebo	4.00	± 0.592
DBT Period: Prasinezumab	3.61	± 0.597

DBT Period: Change in Bradykinesia and Rigidity From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore Secondary · From baseline up to Week 76

MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. For bradykinesia, subscore ranges from 0 to 52, while rigidity subscore ranges from 0 to 20, with higher scores indicating greater impairment. Change in bradykinesia and rigidity was assessed in "OFF" medication state. Adjusted mean is reported here.

Group	Value	95% CI
DBT Period: Placebo	2.77	± 0.476
DBT Period: Prasinezumab	2.85	± 0.479

DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · From study start to end of DBT period to at least 76 weeks

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolong

AEs

Group	Value	95% CI
DBT Period: Placebo	260
DBT Period: Prasinezumab	267

SAEs

Group	Value	95% CI
DBT Period: Placebo	34
DBT Period: Prasinezumab	34

DBT Period: Number of Participants With Adverse Events of Special Interest (AESI) Secondary · From study start to end of DBT period to at least 76 weeks

An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated alanine transaminase (ALT) \& aspartate aminotransferase (AST) in combination with either an elevated

Group	Value	95% CI
DBT Period: Placebo	0
DBT Period: Prasinezumab	0

DBT Period: Number of Participants With Treatment Discontinuation Due to AEs Secondary · From study start to end of DBT period to at least 76 weeks

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Group	Value	95% CI
DBT Period: Placebo	3
DBT Period: Prasinezumab	2

DBT Period: Number of Participants With Infusion Related Reactions (IRRs) Secondary · From study start to end of DBT period to at least 76 weeks

IRRs were defined as any signs and symptoms (AEs) occurring during infusion and/or within 24 hours administration after the end of infusion and were considered related to study treatment by the investigator. Symptoms include flushing, rash, respiratory difficulty, hypotension, tachycardia.

Group	Value	95% CI
DBT Period: Placebo	37
DBT Period: Prasinezumab	32

DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Secondary · From study start to end of DBT period to at least 76 weeks

C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with

Passive: Wish to be Dead

Group	Value	95% CI
DBT Period: Placebo	6
DBT Period: Prasinezumab	5

Non-specific Active Suicidal Thoughts

Group	Value	95% CI
DBT Period: Placebo	2
DBT Period: Prasinezumab	2

Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act

Group	Value	95% CI
DBT Period: Placebo	3
DBT Period: Prasinezumab	0

Self-injurious Behavior, no Suicidal Intent

Group	Value	95% CI
DBT Period: Placebo	0
DBT Period: Prasinezumab	1

Adverse events — posted to ClinicalTrials.gov

Time frame: From study start until the end of DBT period for at least 76 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DBT Period: Placebo

Serious: 34/290 (12%)

Deaths: 2/290

DBT Period: Prasinezumab

Serious: 34/292 (12%)

Deaths: 1/292

Serious adverse events (75 terms)

Reaction	System	DBT Period: Placebo	DBT Period: Prasinezumab
Acute myocardial infarction	Cardiac disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Bradycardia	Cardiac disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Epiretinal membrane	Eye disorders	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Oesophageal food impaction	Gastrointestinal disorders	—	—
Oesophageal perforation	Gastrointestinal disorders	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—
Cyst	General disorders	—	—
Infusion site reaction	General disorders	—	—
Oedema	General disorders	—	—
Bile duct stone	Hepatobiliary disorders	—	—
Cholangitis	Hepatobiliary disorders	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—

Other adverse events (18 terms — click to expand)

Reaction	System	DBT Period: Placebo	DBT Period: Prasinezumab
COVID-19	Infections and infestations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Fall	Injury, poisoning and procedural complications	—	—
Urinary tract infection	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Fatigue	General disorders	—	—
Influenza	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Insomnia	Psychiatric disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—

Most-reported serious reactions: Acute myocardial infarction, Inguinal hernia, Urinary tract infection, Fall, Femur fracture, Back pain, Osteoarthritis, Prostate cancer.

Data from ClinicalTrials.gov NCT04777331 adverse events section.

Sponsor's own description

This is a multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy and safety of intravenous (IV) prasinezumab versus placebo in participants with Early Parkinson's Disease (PD) who are on stable symptomatic PD medication.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction.
   Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, et al · · 2023 · cited 473× · PMID 36859484 · DOI 10.1038/s41419-023-05672-9
2. Signaling pathways in Parkinson's disease: molecular mechanisms and therapeutic interventions.
   Dong-Chen X, Yong C, Yang X, Chen-Yu S, et al · · 2023 · cited 258× · PMID 36810524 · DOI 10.1038/s41392-023-01353-3
3. Alpha-Synuclein Aggregation Pathway in Parkinson's Disease: Current Status and Novel Therapeutic Approaches.
   Vidović M, Rikalovic MG. · · 2022 · cited 117× · PMID 35681426 · DOI 10.3390/cells11111732
4. Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.
   Pagano G, Taylor KI, Anzures Cabrera J, Simuni T, et al · · 2024 · cited 81× · PMID 38622249 · DOI 10.1038/s41591-024-02886-y
5. Therapeutics in the Pipeline Targeting <i>α</i>-Synuclein for Parkinson's Disease.
   Grosso Jasutkar H, Oh SE, Mouradian MM. · · 2022 · cited 69× · PMID 35017177 · DOI 10.1124/pharmrev.120.000133
6. Emerging Therapeutic Strategies for Parkinson's Disease and Future Prospects: A 2021 Update.
   Gouda NA, Elkamhawy A, Cho J. · · 2022 · cited 57× · PMID 35203580 · DOI 10.3390/biomedicines10020371
7. Recent Advances in Drug Therapy for Parkinson's Disease.
   Murakami H, Shiraishi T, Umehara T, Omoto S, et al · · 2023 · cited 57× · PMID 35110492 · DOI 10.2169/internalmedicine.8940-21
8. The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation.
   Karvandi MS, Sheikhzadeh Hesari F, Aref AR, Mahdavi M. · · 2023 · cited 51× · PMID 36950516 · DOI 10.3389/fncel.2023.1105247