Serine and Fenofibrate Study in Patients With MacTel Type 2 (SAFE)

Phase 2a Study of the Effect of Serine Supplementation and Fenofibrate Treatment on Serum Deoxysphinganine Levels in Patients With Macular Telangiectasia (MacTel) Type 2 (SAFE Study)

This is a Phase 2a study of the effect of serine supplementation and fenofibrate treatment on serum deoxysphingolipid levels in patients with macular telangiectasia type 2 (MacTel). This study involves six arms. Participants will be randomly assigned to one of the following treatment groups: serine 200 mg/kg/day, serine 400 mg/kg/day, fenofibrate 160 mg/day, both serine 200 mg/kg/day and fenofibrate 160 mg/day, both serine 400 mg/kg/day and fenofibrate 160 mg/day, or no treatment (control group). Serum deoxysphingolipid levels will be used as the primary outcome, and safety will be evaluated. The participants will be followed for 10 weeks, with visits at Screening, Week 0, 3, 6 and 10.

Study Overview

• Status: Active, not recruiting
• Conditions: Macular Telangiectasia Type 2
• Intervention / Treatment: Dietary supplement: Serine; Drug: Fenofibrate

Detailed Description

Additional Procedures include:

1. Fasting blood work
2. Collection of microbiome samples

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, ECV2PD
    • Moorfields Eye Hospital
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Kellogg Eye Center, University of Michigan
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Retina Associates of Cleveland
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Moran Eye Center, University of Utah
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Eye Institute, Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed and dated written informed consent obtained from the participant in accordance with the local regulations;
2. Males/females 21 years of age or older;
3. English speaking;
4. Enrolled in the Natural History Observation and Registry Study (NHOR) and diagnosed with confirmed MacTel type 2 in at least one eye;
5. Willing to use contraception, if applicable; and
6. Willing to comply with study protocol and follow-up visits.

Exclusion Criteria:

1. Participant is unable to provide informed consent;
2. Participant is less than 21 years of age;
3. Participant is currently taking, or has taken within four weeks prior to screening, a serine or glycine supplement;
4. Participant is currently taking, or has taken within 12 months prior to screening, fibrates including clofibrate, ciprofibrate, bezafibrate, fenofibrate, and gemfibrozil;
5. Participant is currently taking an anticoagulant, colchicine, cyclosporine, tacrolimus or bile acid binding resins;
6. Participant has known allergy to fibrates and/or serine;
7. Participant has a known history of clinically significant myopathy or myalgia related to cholesterol-lowering drugs;
8. Participant has active liver disease and/or elevated liver enzymes*;
9. Participant has renal dysfunction as evidenced by elevated serum creatinine* and/ or glomerular filtration rate (GFR) less than 90 mL/min;
10. Participant has thrombocytopenia as evidenced by a platelet count below 100,000 per microliter, anemia as evidenced by hemoglobin levels below 10 g/dL, or history of bleeding disorder;
11. Participant has a history of gallbladder disease or has had a cholecystectomy;
12. Participant has triglyceride levels greater than 400 mg/dL on treatment, or greater than 700 mg/dL on no treatment;
13. Participant has untreated/uncured Hepatitis C, or a history of Hepatitis B, autoimmune hepatitis, or HIV;
14. Participant has had any malignancies within the last 5 years (not including basal cell carcinoma);
15. Participant has ever been enrolled in a clinical trial involving ciliary neurotrophic factor (CNTF) treatment;
16. Participant is currently enrolled in another clinical trial that involves treatment or participated in one within the last 30 days;
17. Participant is pregnant, breastfeeding or planning a pregnancy;
18. Participant is medically unable to comply with study procedures or follow-up visits;
19. Participant has, in the opinion of the Investigator, any physical or mental condition that would increase the patient's risk of participation in the study or may interfere with the study procedures, evaluations and outcome assessments; or
20. Patient is unavailable for follow-up visits. *based on reference range for the local laboratory used

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Serine 200 mg/kg/day; Serine 200 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)).	Dietary supplement: Serine; Powdered serine supplement (Dosed out individually per participant. Participant to mix with water and ingest orally)
Experimental: Serine 400 mg/kg/day; Serine 400 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)).	Dietary supplement: Serine; Powdered serine supplement (Dosed out individually per participant. Participant to mix with water and ingest orally)
Experimental: Fenofibrate 160 mg/day; Fenofibrate 160 mg per day. To be taken once per day for 6 weeks.	Drug: Fenofibrate; Fenofibrate 160mg pill, taken orally
Experimental: Serine 200 mg/kg/day and Fenofibrate 160 mg/day; Serine 200 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)). Fenofibrate 160 mg per day. To be taken once per day for 6 weeks.	Dietary supplement: Serine; Powdered serine supplement (Dosed out individually per participant. Participant to mix with water and ingest orally); Drug: Fenofibrate; Fenofibrate 160mg pill, taken orally
Experimental: Serine 400 mg/kg/day and Fenofibrate 160 mg/day; Serine 400 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)). Fenofibrate 160 mg per day. To be taken once per day for 6 weeks.	Dietary supplement: Serine; Powdered serine supplement (Dosed out individually per participant. Participant to mix with water and ingest orally); Drug: Fenofibrate; Fenofibrate 160mg pill, taken orally
No Intervention: No treatment; Control group: no investigational product taken

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Deosxysphingolipid Levels	Any changes in serum deoxysphingolipid levels measured (determined via serum sample) at 3 weeks, 6 weeks, and/or 10 weeks when compared with baseline levels measured in week 0	blood draws from week 3, 6, and 10
Safety Assessment	Safety assessment measured via examined AEs and SAEs (during study visits) and via participant self-reported AEs and SAEs that occurred between visits	Assessment at each study visit (reviewed at week 3, week 6, and week 10 of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Levels	Any changes in lipid levels measured (determined via blood tests) at 3 weeks, 6 weeks, and/or 10 weeks when compared with baseline levels measured at screening	blood draws from week 3, 6, and 10
Amino Acid Levels	Any changes in amino acid levels measured (determined via blood tests) at 3 weeks, 6 weeks, and/or 10 weeks when compared with baseline levels measured at screening	blood draws from week 3, 6, and 10

Collaborators and Investigators

• Sponsor: The Lowy Medical Research Institute Limited
• Investigators: Principal Investigator: Mari A Gantner, PhD, Lowy Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Telangiectasis; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: 2020-002

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
• product manufactured in and exported from the U.S.: Yes