NAC Attack, A Phase III, Multicenter, Randomized, Parallel, Double Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral N-Acetylcysteine in Patients with Retinitis Pigmentosa
- Trial ID
- 2022-501438-46-00
- Sponsor
- Johns Hopkins University
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase III, multicenter, randomized, parallel, double-masked, placebo-controlled study is to evaluate the **efficacy** of oral N-Acetylcysteine (NAC) at a dosage of 1800 mg administered twice daily in maintaining visual function and thereby reducing visual disability in patients with **Retinitis Pigmentosa**. This objective is clinically relevant as it addresses the potential of NAC to preserve vision in a progressive degenerative eye disease, which could significantly impact the quality of life for affected individuals. Additionally, the study aims to assess the long-term **safety** and **tolerability** of NAC over a period of 45 months, providing valuable data on the sustained use of this therapeutic intervention.
Participants
The clinical trial involves a total of **378 participants** diagnosed with **Retinitis Pigmentosa**, a genetic disorder affecting the retina. The study population includes both male and female subjects, aged between 18 and 65 years. Participants were selected based on their ability and willingness to provide informed consent and comply with the study protocol. The trial excludes individuals who are unable to participate in all study visits and assessments. Candidates of childbearing potential are required to use a method of contraception and agree not to take supplements other than vitamin A. The trial does not involve a vulnerable population, and participants are expected to maintain their usual lifestyle, with specific attention to dietary supplements. The study aims to evaluate the efficacy and long-term safety of oral NAC 1800 mg administered twice daily over a period of 45 months.
Plans and Procedures
The clinical trial is a **Phase III**, multicenter, randomized, parallel, double-masked, placebo-controlled study designed to evaluate the efficacy and safety of oral **N-Acetylcysteine** (NAC) in patients with **retinitis pigmentosa**. The primary objective is to assess the efficacy of NAC 1800 mg administered twice daily in maintaining visual function and reducing visual disability over a period of 45 months. The trial will also evaluate the long-term safety and tolerability of this treatment regimen. The study is expected to commence recruitment on January 5, 2023, and conclude by January 5, 2028.
Participants will be randomly assigned to receive either the active treatment, **Fluimucil long 600 mg Brausetabletten**, or a placebo, both administered as effervescent tablets. The trial will include a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age (18-65 years), ability to provide informed consent, and willingness to comply with the study protocol. Participants must also agree not to take supplements other than vitamin A and, if of childbearing potential, to use a method of contraception.
Following the screening visit, participants will attend regular follow-up visits to monitor treatment efficacy and safety. The primary efficacy endpoint is the progressive loss in ellipsoid zone (EZ) width, assessed as the cumulative loss of EZ between baseline and month 45, measured using spectral domain-optical coherence tomography (SD-OCT). Secondary endpoints include changes in mean macular sensitivity and best-corrected visual acuity (BCVA) from baseline to month 45.
The expected duration of participant involvement is up to 45 months, with conditions for early termination including non-compliance with the study protocol or withdrawal of consent. The study is not classified as low intervention, and the trial phase is categorized as Phase III. The trial aims to provide valuable insights into the potential benefits of NAC in managing retinitis pigmentosa, a rare disease characterized by progressive vision loss.
Treatment
The clinical trial involves the administration of **Fluimucil long 600 mg Brausetabletten**, an experimental medication containing the active substance **acetylcysteine**. This medication is provided in the form of effervescent tablets, which are dissolved to create an **oral solution**. The dosage regimen for the trial is 1800 mg of acetylcysteine administered twice daily, with a maximum daily dose of 3600 mg. The route of administration is via drinking water. The treatment period is set for a maximum of 45 days. The medication is chemically synthesized and is manufactured by Zambon GmbH. To maintain blinding in the study, secondary packaging involves placing multiple blisters in a wallet and applying a clinical trial label.
The study also includes a **placebo** group, which receives **Acetylcysteine 600 mg PLACEBO, effervescent tablets**. These tablets are designed to mimic the appearance and administration method of the active treatment but do not contain the active substance. The placebo is used to ensure the study's double-masked design, allowing for an unbiased comparison of the efficacy and safety of the active treatment against a non-active control. The placebo is administered with the same frequency and route as the active treatment, ensuring consistency in the trial protocol.
Efficacy
The efficacy of oral N-Acetylcysteine (NAC) in patients with **retinitis pigmentosa** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the evaluation of the progressive loss in ellipsoid zone (EZ) width. This will be assessed by calculating the cumulative loss of EZ, measured as the area under the curve (AUC) between baseline and month 45 (M45). The EZ width will be measured using spectral domain-optical coherence tomography (SD-OCT) scans through the fovea.
Secondary efficacy endpoints include the assessment of changes from baseline in mean macular sensitivity and best-corrected visual acuity (BCVA). Mean macular sensitivity will be measured by microperimetry (MP) at M45, while BCVA will be evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at the same time point. These assessments will provide a comprehensive evaluation of the relative efficacy of NAC 1800 mg taken twice daily compared to placebo in maintaining visual function and reducing visual disability in the study population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability and willingness to provide informed consent • Age ≥ 18 and ≤65 years at time of signing Informed Consent Form • Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator’s judgement • For candidates of childbearing potential: willingness to use a method of contraception • Agreement not to take supplements other than vitamin A
Exclusion Criteria
- General Exclusion Criteria • Active cancer within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score ≤ 6 and stable prostate specific antigen for > 12 months • Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis during the study • Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease (COPD), history of thrombocytopenia not due to a reversible cause or other blood dyscrasia • Uncontrolled blood pressure (defined as systolic > 180 and/or diastolic > 100 mmHg while at rest) at screening. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be controlled by antihypertensive medication, the patient may become eligible if medication is taken continuously for at least 30 days. • History of other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion that oral NAC may be contraindicated or that follow up may be jeopardized • Cerebrovascular accident or myocardial infarction within 6 months of screening • Participation in an investigational study that involves treatment with any drug or device within 6 months of screening • Three relatives already enrolled in study • Pregnant, breast feeding, or intending to become pregnant during the study treatment period. Women of childbearing potential who have not had tubal ligation must have a urine pregnancy test at screening. • Known history of allergy to NAC • Having taken NAC in any form in the past 4 months • Phenylketonuria • Fructose intolerance • Glucose-galactose malabsorption • Sucrase-isomaltase insufficiency • Abnormal laboratory value including the value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper limit of normal • Any major abnormal findings on blood chemistry, hematology, and renal function lab tests that in the opinion of the Site Investigator and/or the Study Chair makes the candidate not suitable to participate in the trial • HIV or hepatitis B infection. • Severe angina that requires frequent administration of nitrates
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 05 Jan 2023 | 30 |
 Germany | Not Recruiting | 05 Jan 2023 | 30 |
 The Netherlands | Not Recruiting | 05 Jan 2023 | — |
| Netherlands | — | — | 60 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Fluimucil long 600 mg Brausetabletten | Test | BRAUSETABLETTEN | IN DRINKING WATER USE | 3600 | 45 | PRD1946876 |
Acetylcysteine 600 mg PLACEBO, effervescent tablets | Placebo | N/A | — | — | — | N/A |