A first-in-human (FIH) clinical trial to investigate the human monoclonal antibody NG004, administrated intrathecally in acute spinal cord injury (SCI) patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NovaGo Therapeutics AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Dec 2024 → ongoing

Decision date (initial)

2024-11-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

NovaGo Therapeutics AG

External identifiers

EU CT number

2024-514303-34-00

WHO UTN

U1111-1308-9590

ClinicalTrials.gov

NCT06817577

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

To evaluate the safety and tolerability of repeated intrathecal (i.t.) bolus injections ([CCI] injections over [CCI] weeks) of NG004 in acute SCI patients

Secondary objectives 1

1. To assess the pharmacokinetics (PK) of NG004

Conditions and MedDRA coding

Acute Incomplete Cervical Spinal Cord Injury

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

Yes

IPD plan description

The following data will be shared: Individual Participant Data that underlie the results that will be reported in future publications, after deidentification (text, tables, figures, and appendices). The data might be shared with researchers who provide a methodologically sound proposal after signing a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female
2. 18 to 75 years of age, inclusive
3. Acute incomplete cervical SCI (Neurological level of injury C1 ≤ lesion ≤ C8) with a) confirmed classification of American Spinal Injury Association (ASIA) impairment scale [CCI] at Screening and b) Nodes [CCI] according to the unbiased recursive partitioning (URP) prediction model for predicted mean UEMS recovery c) UEMS at Screening and Baseline <[CCI]
4. Trial treatment can be initiated by first i.t. bolus injection upon eligibility confirmation within 4-28 days post-injury
5. Tetraplegic patients who are allowed to start treatment are those who either do not require mechanical ventilation or who do not completely depend on mechanical ventilation but show some degree of spontaneous ventilation. Only those modes of ventilation where the patients show active initiation of breathing are allowed (eg, continuous positive airway pressure)
6. Hemodynamically and clinically stable according to the acute SCI condition at Baseline
7. For patients of childbearing potential, use of reliable means of contraception as described below during the treatment phase and for at least 6 months after the last dose of IP: a) Men and women of childbearing potential, who are willing to use a highly effective method of contraception [either combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner or sexual abstinence)], or women not of childbearing potential, defined as women who have been surgically sterilized (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization) or have been postmenopausal for at least 2 years. Individuals who are convincingly sexually abstinent are also eligible. b) Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
8. Written informed consent by patient or witness (for patients who could consent only verbally), provided prior to participation in the trial
9. Cooperation and willingness to complete all aspects of the trial
10. Ability of patient to understand character and individual consequences of the trial

Exclusion criteria 18

1. Trauma caused by ballistic or other injury that directly penetrates the spinal cord including gunshot and knife wounds
2. Multiple levels of clinically relevant spinal cord lesions (CAVE: patients with stable fractures eg, on a thoracic level can be included)
3. Major brachial or lumbar plexus damage/trauma
4. Significant head trauma (eg, cortical damage/lesion), or other injury that is, in the opinion of the investigator, sufficient to interfere with the assessment of the spinal cord function or may otherwise compromise the validity of the patient’s data
5. Other significant pre-existing or current severe systemic diseases such as lung, liver (exception: history of uncomplicated hepatitis A), gastrointestinal, cardiac, immunodeficiency (including anamnestic known HIV) or kidney disease; or active malignancy or any other condition as determined by history or laboratory investigation that could cause a neurological deficit including syphilis, myelopathy, clinically relevant polyneuropathy, etc.
6. History of or an acute episode of Multiple Sclerosis or Guillain-Barre syndrome
7. History of recent meningitis or meningoencephalitis (within last 6 months before Baseline)
8. History of refractory epilepsy
9. Patients with uncontrolled bleeding diathesis and/or who require concomitant therapeutic anticoagulation (eg, phenoprocoumon [Marcumar®], heparin/heparinoids and new oral anticoagulants at a higher dose than for the prophylaxis of venous thromboembolism) and not related to SCI
10. Presence of any unstable medical or psychiatric condition (defined by the Diagnostic and Statistical Manual of Mental Disorders, Edition 4 [DSM-IV]) that may expose the patient to an unwarranted risk from participation in the trial or result in a significant deterioration of the patient’s clinical course
11. Drug dependence (as defined by DSM-IV) any time within last 6 months before Baseline
12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a woman after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test (>5 mIU/mL)
13. History of a life-threatening allergic or immune-mediated reaction
14. Patients with the presence of infection around the location where the spinal needle insertions are planned for applying the intrathecal injections
15. Inability to communicate effectively with the neurological examiner such that the validity of the patient’s data may be compromised
16. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations
17. Patients who are unconscious, including those patients who are unconscious due to medication causing marked sedation
18. Known hypersensitivity to any excipients of the IP or to any drug with similar chemical structure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Type, frequency, severity, and causal relationship of adverse events (AEs), serious AEs (SAEs), and adverse drug reactions (ADRs)
2. Safety laboratory, electrocardiogram (ECG), vital signs, physical and neurological examination, muscle spasticity (Modified Ashworth Scale), and pain (condensed version of the EMSCI Pain Assessment Form [NePAF])

Secondary endpoints 1

1. PK parameter in serum and NG004 concentration in cerebrospinal fluid (CSF)

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NovaGo Therapeutics AG

Sponsor organisation

NovaGo Therapeutics AG

Address

Wagistrasse 27

City

Schlieren

Postcode

8952

Country

Switzerland

Scientific contact point

Organisation

NovaGo Therapeutics AG

Contact name

Director of Clinical Research

Public contact point

Organisation

NovaGo Therapeutics AG

Contact name

Director of Clinical Research

Third parties 4

Locations

1 EU/EEA country · 4 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

Documents 15 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